Biology Unit 1 Notes

AS 8lology Unlt 1 page 1
HGS 8lology A-level notes NCM/7/11

AQA A5 BioIogy Unit 1
Contents
Specltlcatlon 2
8lologlcal Molecules Cbemlcal bonos 4
Carbobyorates 6
Llplos 8
Protelns 10
8locbemlcal Tests 16
Lnzymes 17
Cells Lukaryotlc Cells 24
Prokaryotlc Cells 28
Cell Fractlonatlon 30
Mlcroscopy 31
Tbe Cell Membrane 35
Movement across Cell Membranes 37
Human Pbyslology Lcbange 44
Tbe Gas Lcbange System 46
Lung Dlseases 50
Tbe Heart 54
Coronary Heart Dlsease 58
Tbe Dlgestlve System 60
Cbolera 67
Dlsease Lltestyle ano Dlsease 68
Detence agalnst Dlsease 72
|mmunlsatlon 80
Monoclonal Antlbooles 81
Appenolces 1 Matbematlcal Requlrements 83
2 Tbe Unlt 1 Lam 86

Tbese notes may be useo treely by A level blology stuoents ano teacbers,
ano tbey may be copleo ano eolteo.
Please oo not use tbese materlals tor commerclal purposes.
| woulo be lnteresteo to bear ot any comments ano correctlons.

Nell C Mlllar (nmlllar@ntlworlo.co.uk)
Heao ot 8lology, Heckmonowlke Grammar Scbool
Hlgb Street, Heckmonowlke, WF16 0AH
[uly 2011

BioIogy Unit 1 5pecification

Biochenistry
BioIogicaI MoIecuIes
8lologlcal molecules sucb as carbobyorates ano
protelns are otten polymers ano are baseo on a small
number ot cbemlcal elements.
Protelns bave a varlety ot tunctlons wltbln all llvlng
organlsms. Tbe general structure ot an amlno aclo.
Conoensatlon ano tbe tormatlon ot peptloe bonos
llnklng togetber amlno aclos to torm polypeptloes.
Tbe relatlonsblp between prlmary, seconoary,
tertlary ano quaternary structure, ano proteln
tunctlon.
Monosaccbarloes are tbe baslc molecular unlts
(monomers) ot wblcb carbobyorates are composeo.
Tbe structure ot -glucose ano tbe llnklng ot -
glucose by glycoslolc bonos tormeo by
conoensatlon to torm maltose ano starcb. Sucrose
ls a olsaccbarloe tormeo by conoensatlon ot glucose
ano tructose. Lactose ls a olsaccbarloe tormeo by
conoensatlon ot glucose ano galactose.
Glycerol ano tatty aclos comblne by conoensatlon to
proouce trlglycerloes. Tbe R-group ot a tatty aclo may be
saturateo or unsaturateo. |n pbospbollplos, one ot tbe tatty
aclos ot a trlglycerloe ls substltuteo by a pbospbate group.

BiochenicaI Tests
|oolne/potasslum looloe solutlon tor starcb. 8eneolct's
reagent tor reouclng sugars ano non-reouclng sugars.
Tbe bluret test tor protelns. Tbe emulslon test tor
llplos.

Enzynes
Lnzymes as catalysts lowerlng actlvatlon energy
tbrougb tbe tormatlon ot enzyme-substrate
complees. Tbe lock ano key ano lnouceo tlt mooels ot
enzyme actlon. Use tbe lock ano key mooel to eplaln
tbe propertles ot enzymes. Recognlse lts llmltatlons
ano be able to eplaln wby tbe lnouceo tlt mooel
provloes a better eplanatlon ot specltlc enzyme
propertles. Tbe propertles ot enzymes relatlng to
tbelr tertlary structure.

Descrlptlon ano eplanatlon ot tbe ettects ot
temperature, competltlve ano non-competltlve
lnblbltors, pH ano substrate concentratlon. |nvestlgate
tbe ettect ot a specltlc varlable on tbe rate ot reactlon
ot an enzyme-controlleo reactlon.

CeII BioIogy
CeIIs
Tbe appearance, ultrastructure ano tunctlon ot plasma
membrane, mlcrovllll, nucleus, mltocbonorla,
lysosomes, rlbosomes, enooplasmlc retlculum ano
Golgl apparatus. Apply tbelr knowleoge ot tbese
teatures ln eplalnlng aoaptatlons ot otber eukaryotlc
cells.

Tbe structure ot prokaryotlc cells to lncluoe cell wall,
plasma membrane, capsule, clrcular DNA, tlagella ano
plasmlo.

Microscopes and CeII Fractionation
Tbe oltterence between magnltlcatlon ano resolutlon.
Tbe prlnclples ano llmltatlons ot transmlsslon ano
scannlng electron mlcroscopes. Prlnclples ot cell
tractlonatlon ano ultracentrltugatlon as useo to
separate cell components.

PIasna Menbranes
Tbe arrangement ot pbospbollplos, protelns ano
carbobyorates ln tbe tlulo-mosalc mooel ot membrane
structure. Use tbe tlulo mosalc mooel to eplaln
approprlate propertles ot plasma membranes.
Tbe role ot carrler protelns ano proteln cbannels ln
tacllltateo olttuslon.
Osmosls ls a speclal case ot olttuslon ln wblcb water
moves trom a solutlon ot blgber water potentlal to
a solutlon ot lower water potentlal tbrougb a
partlally permeable membrane. |nvestlgate tbe
ettect ot solute concentratlon on tbe rate ot uptake
ot water by plant lssue.
Tbe role ot carrler protelns ano tbe transter ot
energy ln tbe actlve transport ot substances agalnst
a concentratlon graolent.

PhysioIogy
Exchange
Dlttuslon ls tbe passlve movement ot substances oown
a concentratlon graolent. Surtace area, oltterence ln
concentratlon ano tbe tblckness ot tbe ecbange
surtace attect tbe rate ot olttuslon.

Gas Exchange 5ysten
Tbe gross structure ot tbe buman gas ecbange
system llmlteo to tbe alveoll, broncbloles, broncbl,
tracbea ano lungs. Tbe essentlal teatures ot tbe
alveolar epltbellum as a surtace over wblcb gas
ecbange takes place. Tbe ecbange ot gases ln tbe
lungs. Tbe mecbanlsm ot breatblng. Pulmonary
ventllatlon as tbe proouct ot tloal volume ano
ventllatlon rate.

Lung Diseases
Tbe course ot lntectlon, symptoms ano transmlsslon ot
pulmonary tuberculosls. Tbe ettects ot tlbrosls, astbma
ano empbysema on lung tunctlon. Lplaln tbe
symptoms ot olseases ano conoltlons attectlng tbe
lungs ln terms ot gas ecbange ano resplratlon.
|nterpret oata relatlng to tbe ettects ot pollutlon ano
smoklng on tbe lncloence ot lung olsease. Analyse ano
lnterpret oata assoclateo wltb specltlc rlsk tactors ano
tbe lncloence ot lung olsease.


Heart
Heart structure ano tunctlon. Tbe gross structure ot
tbe buman beart ano lts assoclateo blooo vessels ln
relatlon to tunctlon. Myogenlc stlmulatlon ot tbe beart
ano transmlsslon ot a subsequent wave ot electrlcal
actlvlty. Roles ot tbe slnoatrlal nooe (SAN),
atrloventrlcular nooe (AvN) ano bunole ot Hls.
Pressure ano volume cbanges ano assoclateo valve
movements ourlng tbe carolac cycle. Canoloates
sboulo be able to analyse ano lnterpret oata relatlng to
pressure ano volume cbanges ourlng tbe carolac cycle.
Carolac output as tbe proouct ot beart rate ano
stroke volume. |nvestlgate tbe ettect ot a specltlc
varlable on buman beart rate or pulse rate.

Coronary Heart Disease
Atberoma as tbe presence ot tatty materlal wltbln tbe
walls ot arterles. Tbe llnk between atberoma ano tbe
lncreaseo rlsk ot aneurysm ano tbrombosls.
Myocarolal lntarctlon ano lts cause ln terms ot an
lnterruptlon to tbe blooo tlow to beart muscle. Rlsk
tactors assoclateo wltb coronary beart olsease: olet,
blooo cbolesterol, clgarette smoklng ano blgb blooo
pressure. Descrlbe ano eplaln oata relatlng to tbe
relatlonsblp between specltlc rlsk tactors ano tbe
lncloence ot coronary beart olsease.

Digestive 5ysten
Tbe gross structure ot tbe buman olgestlve system
llmlteo to oesopbagus, stomacb, small ano large
lntestlnes ano rectum. Tbe glanos assoclateo wltb tbls
system llmlteo to tbe sallvary glanos ano tbe pancreas.
Tbe structure ot an epltbellal cell trom tbe small
lntestlne as seen wltb an optlcal mlcroscope.

Dlgestlon ls tbe process ln wblcb large molecules are
byorolyseo by enzymes to proouce smaller molecules
tbat can be absorbeo ano asslmllateo. Tbe role ot
sallvary ano pancreatlc amylases ln tbe olgestlon ot
starcb ano ot maltase locateo ln tbe lntestlnal
epltbellum. Dlgestlon ot olsaccbarloes by sucrase ano
lactase. Absorptlon ot tbe prooucts ot carbobyorate
olgestlon. Tbe roles ot olttuslon, actlve transport ano
co-transport lnvolvlng soolum lons. Tbe role ot
mlcrovllll ln lncreaslng surtace area. Lactose
lntolerance.

ChoIera
Tbe cbolera bacterlum as an eample ot a prokaryotlc
organlsm. Cbolera bacterla proouce tolns tbat
lncrease secretlon ot cblorloe lons lnto tbe lumen ot
tbe lntestlne. Tbls results ln severe olarrboea. Tbe use
ot oral rebyoratlon solutlons (ORS) ln tbe treatment
ot olarrboeal olseases. Dlscuss tbe appllcatlons ano
lmpllcatlons ot sclence ln oeveloplng lmproveo oral
rebyoratlon solutlons, ano etblcal lssues assoclateo
wltb trlalllng lmproveo oral rebyoratlon solutlons on
bumans.

Disease
LifestyIe and Disease
Dlsease may be causeo by lntectlous patbogens or may
retlect tbe ettects ot lltestyle.
Patbogens lncluoe bacterla, vlruses ano tungl.
Dlsease can result trom patbogenlc mlcroorganlsms
penetratlng any ot an organlsm's lntertaces wltb tbe
envlronment. Tbese lntertaces lncluoe tbe olgestlve
ano gas-ecbange systems. Patbogens cause olsease
by oamaglng tbe cells ot tbe bost ano by proouclng
tolns.
Lltestyle can attect buman bealtb. Specltlc rlsk
tactors are assoclateo wltb cancer ano coronary
beart olsease. Cbanges ln lltestyle may also be
assoclateo wltb a reouceo rlsk ot contractlng tbese
conoltlons. Analyse ano lnterpret oata assoclateo
wltb specltlc rlsk tactors ano tbe lncloence ot
olsease. Recognlse correlatlons ano causal
relatlonsblps.

Defence against Disease
Mammallan blooo possesses a number ot oetenslve
tunctlons. Pbagocytosls ano tbe role ot lysosomes ano
lysosomal enzymes ln tbe subsequent oestructlon ot
lngesteo patbogens.

Detlnltlon ot antlgen ano antlbooy. Antlbooy structure
ano tbe tormatlon ot an antlgen-antlbooy comple.
Tbe essentlal oltterence between bumoral ano cellular
responses as sbown by 8 cells ano T cells. Tbe role ot
plasma cells ano memory cells ln proouclng a
seconoary response. Tbe ettects ot antlgenlc varlabllty
ln tbe lntluenza vlrus ano otber patbogens on
lmmunlty.

Vaccines and nonocIonaI antibodies
Tbe use ot vacclnes to provloe protectlon tor
lnolvlouals ano populatlons agalnst olsease. Tbe use ot
monoclonal antlbooles ln enabllng tbe targetlng ot
specltlc substances ano cells.

Lvaluate metbooology, evloence ano oata relatlng to
tbe use ot vacclnes ano monoclonal antlbooles.
Dlscuss etblcal lssues assoclateo wltb tbe use ot
vacclnes ano monoclonal antlbooles. Lplaln tbe role
ot tbe sclentltlc communlty ln valloatlng new
knowleoge about vacclnes ano monoclonal antlbooles
tbus ensurlng lntegrlty. Dlscuss tbe ways ln wblcb
soclety uses sclentltlc knowleoge relatlng to vacclnes
ano monoclonal antlbooles to lntorm oeclslon-maklng.


BioIogicaI MoIecuIes
Llvlng tblngs are maoe up ot tbousanos ano tbousanos ot oltterent cbemlcals. Tbese cbemlcals are calleo
organlc because tbey contaln tbe element carbon. |n sclence organlc compounos contaln carboncarbon
bonos, wblle lnorganlc compounos oon't. Tbere are tour lmportant types ot organlc molecules touno ln
llvlng organlsms: carbobyorates, llplos, protelns, ano nuclelc aclos (DNA). Tbese molecules are mostly
polymers, very large molecules maoe up trom very many small molecules, calleo monomers. 8etween tbem
tbese tour groups make up 93 ot tbe ory mass ot llvlng organlsms, tbe remalnlng 7 comprlslng small
organlc molecules (llke vltamlns) ano lnorganlc lons.

Group nane EIenents Mononers PoIyners dry nass of a ceII
Carbobyorates CHO monosaccbarloes polysaccbarloes 15
Llplos CHOP tatty aclos + glycerol* trlglycerloes* 10
Protelns CHONS amlno aclos polypeptloes 50
Nuclelc aclos CHONP nucleotloes polynucleotloes 18
* Trlglycerloes are not polymers, slnce tbey are tormeo trom just tour molecules, not many (see p8).

We'll stuoy carbobyorates, llplos ano protelns ln oetall now, ano we'll look at nuclelc aclos (DNA) ln unlt 2.

ChenicaI Bonds
|n blocbemlstry tbere are two lmportant types ot cbemlcal bono: tbe covalent bono ano tbe byorogen
bono.
Covalent bonos are strong. Tbey are tbe maln bonos bololng tbe atoms togetber ln
tbe organlc molecules ln llvlng organlsms. 8ecause tbey are strong, covalent bonos
oon't break or torm spontaneously at tbe temperatures touno ln llvlng cells. So ln
blology covalent bonos are always maoe or broken by tbe actlon ot enzymes.
Covalent bonos are representeo by sollo llnes ln cbemlcal structures.

covalent
bonos
H C H
H
H

Hyorogen bonos are mucb weaker. Tbey are tormeo between an atom (usually
byorogen) wltb a sllgbt posltlve cbarge (oenoteo +) ano an atom (usually oygen
or nltrogen) wltb a sllgbt negatlve cbarge (oenoteo ). 8ecause byorogen bonos
are weak tbey can break ano torm spontaneously at tbe temperatures touno ln
llvlng cells wltbout neeolng enzymes. Hyorogen bonos are representeo by ootteo
llnes ln cbemlcal structures.
C N H O
byorogen bono
- +


Water
Llte on Lartb evolveo ln tbe water, ano all llte stlll oepenos on water. At least 80 ot tbe total mass ot llvlng
organlsms ls water. Water molecules are cbargeo, wltb tbe oygen atom belng sllgbtly negatlve (-) ano tbe
byorogen atoms belng sllgbtly posltlve (+). Tbese opposlte cbarges attract eacb otber, tormlng byorogen
bonos tbat blno water molecules loosely togetber.

O
O
O H
H
H
H
H
H
covalent
bonos
byorogen
bonos
+
+
+
+
-
- H
H
O

8ecause lt ls cbargeo, water ls a very gooo solvent, ano almost all tbe cbemlcal reactlons ot llte take place ln
aqueous solutlon.
Cbargeo or polar molecules sucb as salts, sugars, amlno aclos olssolve reaolly ln water ano so are calleo
byoropblllc ("water lovlng").
Uncbargeo or non-polar molecules sucb as llplos oo not olssolve so well ln water ano are calleo
byoropboblc ("water batlng").
Many lmportant blologlcal molecules lonlse wben tbey olssolve (e.g. acetlc aclo acetate
-
+ H
+
), so tbe
names ot tbe aclo ano lonlseo torms (acetlc aclo ano acetate ln tbls eample) are otten useo loosely ano
lntercbangeably, wblcb can cause contuslon. You wlll come across many eamples ot two names reterrlng
to tbe same substance, e.g. pbospborlc aclo ano pbospbate, lactlc aclo ano lactate, cltrlc aclo ano cltrate,
pyruvlc aclo ano pyruvate, aspartlc aclo ano aspartate, etc. Tbe lonlseo torm ls tbe one touno ln llvlng cells.

Water molecules "stlck togetber" oue to tbelr byorogen bonos, so water bas blgb cobeslon. Tbls eplalns
wby long columns ot water can be suckeo up tall trees by transplratlon wltbout breaklng. |t also eplalns
surtace tenslon, wblcb allows small anlmals to walk on water.

Carbohydrates
Carbobyorates contaln only tbe elements carbon, byorogen ano oygen. Tbe group lncluoes monomers,
olmers ano polymers, as sbown ln tbls olagram:
Carbohydrates
Sugars
Monosaccbarloes
(monomers)
e.g. glucose, tructose,
galactose
Polysaccbarloes
(polymers)
e.g. starcb,
cellulose, glycogen
Dlsaccbarloes
(olmers)
e.g. sucrose,
maltose, lactose

Monosaccharides
Tbese all bave tbe tormula (CH2O)n, wbere n can be 3-7. Tbe most common ano lmportant
monosaccbarloe ls glucose, wblcb ls a sl-carbon or beose sugar, so bas tbe tormula C6H12O6. |ts
structure ls:
C
C C
C
C O
H
OH
H
OH
OH
OH
H
H
H H
HO
C
H

or more slmply
OH
O
HO
Glucose

Glucose torms a sl-sloeo rlng, altbougb ln tbree-olmenslons lt torms a structure tbat looks a blt llke a
cbalr. |n anlmals glucose ls tbe maln transport sugar ln tbe blooo, ano lts concentratlon ln tbe blooo ls
caretully controlleo. Tbere are many lsomers ot glucose, wltb tbe same cbemlcal tormula (C6H12O6), but
oltterent structural tormulae. Tbese lsomers lncluoe galactose ano tructose:

Galactose
OH HO
O

O
HO
Fructose

Common tlve-carbon, or pentose sugars (wbere n = 5, C5H10O5) lncluoe rlbose ano oeoyrlbose (touno ln
nuclelc aclos ano ATP, see unlt 2) ano rlbulose (wblcb occurs ln pbotosyntbesls). Tbree-carbon, or trlose
sugars (wbere n = 3, C3H6O3) are also touno ln resplratlon ano pbotosyntbesls (see unlt 4).


Disaccharides
Dlsaccbarloes are tormeo wben two monosaccbarloes are jolneo togetber by a glycoslolc bono (COC).
Tbe reactlon lnvolves tbe tormatlon ot a molecule ot water (H2O):
OH
O
HO
O
O
HO OH
O
HO OH
O
!"#$%&'('$ *%+(
H O
2

Tbls sbows two glucose molecules jolnlng togetber to torm tbe olsaccbarloe maltose. Tbls klno ot reactlon,
wbere two molecules comblne lnto one blgger molecule, ls calleo a conoensatlon reactlon. Tbe reverse
process, wbere a large molecule ls broken lnto smaller ones by reactlng wltb water, ls calleo a byorolysls
reactlon.

|n general: polymerlsatlon reactlons are conoensatlons
breakoown reactlons are byorolyses

Tbere are tbree common olsaccbarloes:
Maltose (or malt sugar) ls glucoseglucose. |t ls tormeo on olgestlon
ot starcb by amylase, because tbls enzyme breaks starcb oown lnto
two-glucose unlts. 8rewlng beer starts wltb malt, wblcb ls a maltose
solutlon maoe trom germlnateo barley.
O
HO OH
O
O
Glucose Glucose

Sucrose (or cane sugar) ls glucosetructose. |t ls common ln plants
because lt ls less reactlve tban glucose, ano lt ls tbelr maln transport
sugar. |t ls tbe common table sugar tbat you put ln your tea.
O
HO
O
O
Fructose
Glucose

Lactose (or mllk sugar) ls galactoseglucose. |t ls touno only ln
mammallan mllk, ano ls tbe maln source ot energy tor lntant
mammals.
OH
O
HO
O
O
Galactose
Glucose

PoIysaccharides
Polysaccbarloes are cbalns ot many glucose monomers (otten 1000s) jolneo togetber by glycoslolc bonos.
Starcb, glycogen ano cellulose are polysaccbarloes. Tbey wlll be stuoleo ln unlt 2.

Lipids
Llplos are a mleo group ot byoropboblc compounos composeo ot tbe elements carbon, byorogen, oygen
ano sometlme pbospborus (CHOP). Tbe most common llplos are trlglycerloes ano pbospbollplos.

TrigIycerides
Trlglycerloes, or trlacylglycerols, are maoe ot glycerol ano tatty aclos.
Glycerol ls a small, 3-carbon molecule wltb
tbree alcobol (OH) groups.
C H C C H
OH OH OH
H H H

Fatty aclos are long molecules maoe ot a non-
polar byorocarbon cbaln wltb a polar carboyl
aclo group at one eno. Tbe byorocarbon cbaln
can be trom 14 to 22 CH2 unlts long. 8ecause
tbe lengtb ot tbe byorocarbon cbaln can vary lt
ls sometlmes calleo an R group, so tbe tormula
ot a tatty aclo can be wrltten as R-COOH.
Carboyl
aclo group
Hyorocarbon cbaln (14-22 carbon atoms)
C C C C C C H
H H H H H H
H H H H H H
C
O
OH
CH (CH ) COOH
3 2 n
R COOH
or
or

One molecule ot glycerol jolns togetber wltb tbree tatty aclo molecules by ester bonos to torm a
trlglycerloe molecule, ln anotber conoensatlon polymerlsatlon reactlon:

OH
OH
OH
H
H
O
R C HO C H
O
R C HO C H
O
R C HO C H
H
H
O
R C O C H
O
R C O C H
O
R C O C H
, -&.-/ *%+(&
3 tatty aclo
molecules
1 glycerol
molecule
1 trlglycerloe
molecule
3 water
molecules
3 H O
2

Trlglycerloes are commonly known as tats or olls, ano are lnsoluble ln water. Tbey are useo tor storage,
lnsulatlon ano protectlon ln tatty tlssue (or aolpose tlssue) touno unoer tbe skln (sub-cutaneous) or
surrounolng organs. Wben ololseo trlglycerloes ylelo more energy per unlt mass tban otber compounos
so are gooo tor energy storage. However, trlglycerloes can't be moblllseo qulckly slnce tbey are so
lnsoluble, so are no gooo tor qulck energy requlrements. Tlssues tbat neeo energy qulckly (llke muscles)
lnsteao store carbobyorates llke glycogen.

|t tbe tatty aclo cbalns ln a trlglycerloe bave no C=C oouble bonos, tben tbey
are calleo saturateo tatty aclos (l.e. saturateo wltb byorogen). Trlglycerloes
wltb saturateo tatty aclos bave a blgb meltlng polnt ano teno to be touno ln
warm-bloooeo anlmals. At room temperature tbey are sollos (tats), e.g. butter,
laro.
C C C C
H H H H
H H H H
saturateo

|t tbe tatty aclo cbalns ln a trlglycerloe oo bave C=C oouble bonos tbey are
calleo unsaturateo tatty aclos (l.e. unsaturateo wltb byorogen). Fatty aclos wltb
more tban one oouble bono are calleo poly-unsaturateo tatty aclos (PUFAs).
Trlglycerloes wltb unsaturateo tatty aclos bave a low meltlng polnt ano teno to
be touno ln colo-bloooeo anlmals ano plants. At room temperature tbey are
llqulos (olls), e.g. tlsb oll, vegetable olls. An omega number ls sometlmes useo
to oenote tbe posltlon ot a oouble bono, e.g. omega-3 tatty aclos.
C C C C
H H
H H H H
unsaturateo

PhosphoIipids
Pbospbollplos bave a slmllar structure to trlglycerloes, but wltb a pbospbate group ln place ot one tatty aclo
cbaln. Tbere may also be otber groups attacbeo to tbe pbospbate. Pbospbollplos bave a polar byoropblllc
"beao" (tbe negatlvely-cbargeo pbospbate group) ano two non-polar byoropboblc "talls" (tbe tatty aclo
cbalns).
glycerol
pbospbate
tatty aclo
tatty aclo
H
H
O
-
O
-
O P O H C
O
R C O C H
O
R C O C H

or
byoropblllc
beao
byoropboblc
talls

Tbls mlture ot propertles ls tunoamental to blology, tor
pbospbollplos are tbe maln components ot cell membranes. Wben
mleo wltb water, pbospbollplos torm oroplet spberes wltb a
oouble-layereo pbospbollplo bllayer. Tbe byoropblllc beaos taclng
tbe water ano tbe byoropboblc talls taclng eacb otber. Tbls traps a
compartment ot water ln tbe mloole separateo trom tbe eternal
water by tbe byoropboblc spbere. Tbls naturally-occurrlng
structure ls calleo a llposome, ano ls slmllar to a membrane
surrounolng a cell (see p35).

pbospbollplo
bllayer
aqueous
compartment


Proteins
Protelns are tbe most comple ano most olverse group ot blologlcal compounos. Tbey bave an astonlsblng
range ot oltterent tunctlons, as tbls llst sbows.

structure e.g. collagen (bone, cartllage, tenoon), keratln (balr), actln (muscle)
enzymes e.g. amylase, pepsln, catalase, etc (>10,000 otbers)
transport e.g. baemoglobln (oygen), transterrln (lron)
pumps e.g. Na
+
K
+
pump ln cell membranes
motors e.g. myosln (muscle), klnesln (cllla)
bormones e.g. lnsulln, glucagon
receptors e.g. rbooopsln (llgbt receptor ln retlna)
antlbooles e.g. lmmunoglobullns
storage e.g. albumlns ln eggs ano blooo, caesln ln mllk
blooo clottlng e.g. tbrombln, tlbrln
lubrlcatlon e.g. glycoprotelns ln synovlal tlulo
tolns e.g. cbolera toln
antltreeze e.g. glycoprotelns ln arctlc tlea
ano many more!

Anino Acids
Protelns are maoe ot amlno aclos. Amlno
aclos are maoe ot tbe tlve elements
C H O N S. Amlno aclos are so-calleo
because tbey contaln botb an amlno group
ano an aclo group. Tbe general structure ot
an amlno aclo molecule ls sbown on tbe
rlgbt. Tbere ls a central carbon atom (calleo
tbe "alpba carbon", C
), wltb tour oltterent

cbemlcal groups attacbeo to lt:
1. a byorogen atom
2. a baslc amlno group (NH2 or
+
3
NH )
3. an aclolc carboyl group (COOH or COO
-
)
4. a varlable "R" group (or sloe cbaln)
R group
carboy
aclo
group
byorogen
amlno
group
C C N
H
H
H
R
O
OH


Tbere are 20 oltterent R groups, ano so 20 oltterent amlno aclos. Slnce eacb R group ls sllgbtly oltterent,
eacb amlno aclo bas oltterent propertles, ano tbls ln turn means tbat protelns can bave a wloe range ot
propertles. Tbe table on page sbows tbe 20 oltterent R groups, groupeo by property, wblcb glves an loea
ot tbe range ot propertles. You oo not neeo to learn tbese, but lt ls lnterestlng to see tbe oltterent
structures, ano you sboulo be tamlllar wltb tbe amlno aclo names. You may alreaoy bave bearo ot some,
sucb as tbe tooo aooltlve monosoolum glutamate, wblcb ls slmply tbe soolum salt ot tbe amlno aclo
glutamate. Tbere are 3-letter ano 1-letter abbrevlatlons tor eacb amlno aclo.

PoIypeptides
Amlno aclos are jolneo togetber by peptloe bonos. Tbe reactlon lnvolves tbe tormatlon ot a molecule ot
water ln anotber conoensatlon polymerlsatlon reactlon:

C C N
H
R
O
OH
H
H
C
H
R
C
O
OH
N
H
H
C
O
OH
N
H
H
C C
H O
R
C N
H
R H
0-0.'(- *%+(
H O
2

Wben two amlno aclos joln togetber a olpeptloe ls tormeo. Tbree amlno aclos torm a trlpeptloe. Many
amlno aclos torm a polypeptloe. e.g.:

H N-Gly Pro Hls Leu Tyr Ser Trp Asp Lys Cys-COOH
2
12.-/3'+4& 52.-/3'+4&

|n a polypeptloe tbere ls always one eno wltb a tree amlno (NH2) group, calleo tbe N-termlnus, ano one
eno wltb a tree carboyl (COOH) group, calleo tbe C-termlnus.

|n a proteln tbe polypeptloe cbaln may be many bunoreos ot amlno aclos long. Amlno aclo polymerlsatlon
to torm polypeptloes ls part ot proteln syntbesls. |t takes place ln rlbosomes, ano ls speclal because lt
requlres an RNA template. Tbe sequence ot amlno aclos ln a polypeptloe cbaln ls oetermlneo by tbe
sequence ot tbe bases ln DNA. Proteln syntbesls ls stuoleo ln oetall ln unlt 5.


Protein 5tructure
Polypeptloes are just strlngs ot amlno aclos, but tbey tolo up ano comblne to torm tbe comple ano well-
oetlneo tbree-olmenslonal structure ot worklng protelns. To belp to unoerstano proteln structure, lt ls
broken oown lnto tour levels:

1. Prinary 5tructure
Tbls ls just tbe sequence ot amlno aclos ln tbe polypeptloe cbaln, so ls not really a structure at all.
However, tbe prlmary structure ooes oetermlne tbe rest ot tbe proteln structure.

2. 5econdary 5tructure
Tbls ls tbe most baslc level ot proteln tololng, ano conslsts ot a tew baslc motlts
tbat are touno ln almost all protelns. Tbe seconoary structure ls belo togetber by
byorogen bonos between tbe carboyl groups ano tbe amlno groups ln tbe
polypeptloe backbone. Tbe two most common seconoary structure motlts are
tbe -bell ano tbe -sbeet.

C N H O
byorogen bono
- +

The -heIix. Tbe polypeptloe cbaln ls wouno
rouno to torm a bell. |t ls belo togetber by
byorogen bonos runnlng parallel wltb tbe long
bellcal als. Tbere are so many byorogen bonos
tbat tbls ls a very stable ano strong structure. Do
not contuse tbe -bell ot protelns wltb tbe
tamous oouble bell ot DNA bellces are common
structures tbrougbout blology.
polypeptloe backbone
byorogen bonos
N
H-N
H-N
H-N
H-N
H-N
C
C
C
C
C
C=O
C=O
C=O
C=O
C=O

The -sheet. Tbe polypeptloe cbaln zlg-zags back
ano torwaro tormlng a sbeet ot antlparallel stranos.
Once agaln lt ls belo togetber by byorogen bonos.
N C
C
O
H
N C
C
O
H
N C
C
O
H
N C
C
O
H
N C
C
O
H
N C
C
O
H
N C
C
O
H
N C
C
O
H
N C
C
O
H
N C
C
O
H
C
N C
O
H
C
N C
O
H
C
N C
O
H
C
N C
O
H
C
N C
O
H
N
C
C O
H
O
HN
C
C


3. Tertiary 5tructure
Tbls ls tbe compact globular structure tormeo by tbe tololng up
ot a wbole polypeptloe cbaln. Lvery proteln bas a unlque tertlary
structure, wblcb ls responslble tor lts propertles ano tunctlon.
For eample tbe sbape ot tbe actlve slte ln an enzyme ls oue to
lts tertlary structure. Tbe tertlary structure ls belo togetber by
bonos between tbe R groups ot tbe amlno aclos ln tbe proteln,
ano so oepenos on wbat tbe sequence ot amlno aclos ls. Tbese
bonos lncluoe weak byorogen bonos ano sulpbur brloges -
covalent SS bonos between two cystelne amlno aclos, wblcb are
mucb stronger.

So tbe seconoary structure ls oue to backbone lnteractlons ano ls tbus largely lnoepenoent ot prlmary
sequence, wblle tertlary structure ls oue to sloe cbaln lnteractlons ano tbus oepenos on tbe amlno aclo
sequence.

4. Quaternary 5tructure
Almost all worklng protelns are actually composeo ot more tban one polypeptloe cbaln, ano tbe quaternary
structure ls tbe arrangement ot tbe oltterent cbalns. Tbere are a buge varlety ot quaternary structures e.g.:

Haemoglobln conslsts ot tour cbalns arrangeo ln a
tetrabeoral (pyramlo) structure.

-S-
-S-
-
S
-
-
S
-

Antlbooles comprlse tour cbalns
arrangeo ln a Y-sbape.

Tbe enzyme ATP syntbase ls composeo ot
22 cbalns tormlng a rotatlng motor.

Collagen conslsts ot tbree cbalns ln
a trlple bell structure.

Actln conslsts ot bunoreos ot globular cbalns
arrangeo ln a long oouble bell.


Tbese tour structures are not real stages ln tbe tormatlon ot a proteln, but are slmply a convenlent
classltlcatlon tbat sclentlsts lnventeo to belp tbem to unoerstano protelns. |n tact protelns tolo lnto all tbese
structures at tbe same tlme, as tbey are syntbeslseo.

Tbe tlnal tbree-olmenslonal sbape ot a proteln can be classltleo as globular or tlbrous.

GIobuIar Proteins
Tbe vast majorlty ot protelns are globular, l.e. tbey
bave a compact, ball-sbapeo structure. Tbls group
lncluoes enzymes, membrane protelns, receptors
ano storage protelns. Tbe olagram below sbows a
typlcal globular enzyme molecule. |t bas been orawn
to blgbllgbt tbe oltterent seconoary structures.

bell
sbeet

Fibrous {or FiIanentous} Proteins
Flbrous protelns are long ano tbln, llke ropes. Tbey
teno to bave structural roles, sucb as collagen
(bone), keratln (balr), tubulln (cytoskeleton) ano
actln (muscle). Tbey are always composeo ot many
polypeptloe cbalns. Tbls olagram sbows part ot a
molecule ot collagen, wblcb ls touno ln bone ano
cartllage.

A tew protelns bave botb structures: tor eample tbe muscle proteln myosln bas a long tlbrous tall ano a
globular beao, wblcb acts as an enzyme (see unlt 4).

Protein Denaturing
Slnce tbe seconoary, tertlary ano quaternary structures are largely belo togetber by byorogen bonos, tbe
tbree-olmenslonal structure ot protelns ls lost lt tbe byorogen bonos break. Tbe polypeptloe cbaln just tolos
up lnto a ranoom coll ano tbe proteln loses lts tunctlon. Tbls ls calleo oenaturlng, ano bappens at
temperatures above about 50C or at very low or blgb pH. Covalent bonos are not broken unoer tbese
conoltlons, so tbe prlmary structure ls malntalneo (as are sulpbur brloges).


The Twenty Anino Acid R-Groups
5inpIe R groups Basic R groups
Glyclne
Gly G
H
Lyslne
Lys K
CH
2
CH
2
CH
2
CH
2
NH
3
+

Alanlne
Ala A
CH
3

Arglnlne
Arg R
CH
2
CH
2
NH C
NH
2
CH
2
NH
2
+

vallne
val v
CH
CH
3
CH
3

Hlstlolne
Hls H
CH
2
C
N
CH
CH
NH
Leuclne
Leu L
CH
2
CH
CH
3
CH
3

Asparaglne
Asn N
CH
2
C
O
NH
2
|soleuclne
|le |
CH CH
2
CH
3
CH
3

Glutamlne
Gln Q
CH
2
CH
2
C
O
NH
2
HydroxyI R groups Acidic R groups
Serlne
Ser S
CH
2
OH

Aspartate
Asp D
CH
2
CH
2
C
O
OH

Tbreonlne
Tbr T
CH OH
CH
3

Glutamate
Glu L
CH
2
C
O
OH

5uIphur R groups Ringed R groups
Cystelne
Cys C
CH
2
SH

Pbenylalanlne
Pbe F
CH
2

Metblonlne
Met M
CH
2
CH
2
S CH
3

Tyroslne
Tyr Y
CH
2
OH

CycIic R group
Prollne
Pro P
NH
H
COOH
CH
2
CH
2
CH
2
C

Tryptopban
Trp W
CH
2
CH
NH
CH


BiochenicaI Tests
Tbese tlve tests loentlty tbe maln blologlcally-lmportant cbemlcal compounos. For eacb test take a small
sample ot tbe substance to test ano, lt lt lsn't alreaoy a solutlon, grlno lt wltb some water to break up tbe
cells ano release tbe cell contents. Many ot tbese compounos are lnsoluble, but tbe tests work just as well
on a tlne suspenslon.
1. 5tarch (loolne test). Aoo a tew orops ot loolne/potasslum looloe solutlon to tbe sample. A blue-black
colour lnolcates tbe presence ot starcb as a starcb-polylooloe comple ls tormeo.
2. Reducing 5ugars (8eneolct's test). All monosaccbarloes ano most olsaccbarloes (ecept sucrose) are
calleo reouclng sugars because tbey wlll reouce lons llke Cu
2+
. Aoo a tew mL ot 8eneolct's reagent to
tbe sample. Sbake, ano beat tor a tew mlnutes at 95C ln a water batb. A coloureo preclpltate lnolcates
reouclng sugar. Tbe colour ano oenslty ot tbe preclpltate glves an lnolcatlon ot tbe amount ot reouclng
sugar present, so tbls test ls seml-quantltatlve. Tbe orlglnal pale blue colour means no reouclng sugar, a
green preclpltate means relatlvely llttle sugar, a brown or reo preclpltate means progresslvely more
sugar ls present.
3. Non-reducing 5ugars (8eneolct's test). Sucrose ls a non-reouclng sugar, so tbere ls no olrect test tor
sucrose. However, lt lt ls tlrst byorolyseo to lts constltuent monosaccbarloes (glucose ano tructose), lt
wlll tben glve a posltlve 8eneolct's test. So sucrose ls tbe only sugar tbat wlll glve a negatlve 8eneolct's
test betore byorolysls ano a posltlve test atterwaros. Flrst test a sample tor reouclng sugars, to see lt
tbere are any present betore byorolysls. Tben, uslng a separate sample, boll tbe test solutlon wltb ollute
byorocblorlc aclo tor a tew mlnutes to byorolyse tbe glycoslolc bono. Neutrallse tbe solutlon by gently
aoolng small amounts ot sollo soolum byorogen carbonate untll lt stops tlzzlng, tben test as betore tor
reouclng sugars.
4. Lipids (emulslon test). Llplos oo not olssolve ln water, but oo olssolve ln etbanol. Tbls cbaracterlstlc ls
useo ln tbe emulslon test. Do not start by olssolvlng tbe sample ln water, but lnsteao vlgorously sbake
some ot tbe test sample wltb about 4 mL ot etbanol. Decant tbe llqulo lnto a secono test tube ot water,
leavlng any unolssolveo substances beblno. |t tbere are llplos olssolveo ln tbe etbanol, tbey wlll
preclpltate ln tbe water, tormlng a clouoy wblte emulslon.
5. Protein (bluret test). Aoo a tew mL ot bluret solutlon to tbe sample. Sbake, ano tbe solutlon turns lllac-
purple, lnolcatlng proteln.

Enzynes
Lnzymes are blologlcal catalysts. Tbere are about 40,000 oltterent enzymes ln buman cells, eacb controlllng
a oltterent cbemlcal reactlon. Tbey lncrease tbe rate ot reactlons by a tactor ot between 10
6
to 10
12
tlmes,
allowlng tbe cbemlcal reactlons tbat make llte posslble to take place at normal temperatures. Tbey were
olscovereo ln termentlng yeast ln 1900 by 8ucbner, ano tbe name enzyme means "ln yeast". As well as
catalyslng all tbe metabollc reactlons ot cells (sucb as resplratlon, pbotosyntbesls ano olgestlon), tbey also
act as motors, membrane pumps ano receptors.


How do enzynes work!
Tbere are tbree ways ot tblnklng about enzyme catalysls. Tbey all oescrlbe tbe same process, tbougb ln
oltterent ways, ano you sboulo know about eacb ot tbem.

1. Enzynes ManipuIate the 5ubstrate in the Active 5ite
Lnzymes are protelns, ano tbelr tunctlon ls oetermlneo by tbelr comple 3-olmentlonal structure. Tbe
reactlon takes place ln a small part ot tbe enzyme calleo tbe actlve slte, wblle tbe rest ot tbe proteln acts as
"scattololng". Tbe substrate molecule blnos to tbe actlve slte ano tbe proouct ls releaseo.

substrate actlve slte
proteln
cbaln
Lysozyne ~ whoIe noIecuIe CIose-up of substrate binding to
anino acids in the active site
substrate
R-groups ot amlno
aclos at tbe actlve slte

Tbere are two mooels tor tbe actlon ot enzyme actlve sltes:
Tbe lock ano key mooel states tbat tbe enzyme's actlve slte ls complementary to tbe substrate
molecule. Tbe actlve slte ls llke a lock ano tbe substrate ls llke a key tlttlng pertectly lnto tbe lock. Tbe
sbape ano propertles ot tbe actlve slte are glven by tbe amlno aclos arouno lt. Tbese amlno aclos torm
weak byorogen ano lonlc bonos wltb tbe substrate molecule, so tbe actlve slte blnos one substrate
only.
Tbe |nouceo tlt mooel states tbat tbe enzyme ls tlelble ano so tbe actlve slte can cbange sbape. Tbe
actlve slte lsn't eactly complementary to tbe substrate, but as tbe substrate starts to blno, tbe actlve
slte cbanges sbape to tlt tbe substrate more closely. Tbls cbange ln turn olstorts tbe substrate molecule
ln tbe actlve slte, maklng lt more llkely to cbange lnto tbe proouct. For eample lt a bono ln tbe
substrate ls to be broken, tbat bono mlgbt be stretcbeo by tbe enzyme, maklng lt more llkely to break.
Alternatlvely lt a bono ls to be maoe between two molecules, tbe two molecules can be belo ln eactly
tbe rlgbt posltlon ano orlentatlon ano pusbeo togetber, maklng tbe bono more llkely to torm. Tbe
enzyme can also make tbe local conoltlons lnsloe tbe actlve slte qulte oltterent trom tbose outsloe
(sucb as pH, water concentratlon, cbarge), so tbat tbe reactlon ls more llkely to bappen. Tbe lnouceo
tlt mooel eplalns tbe actlon ot enzymes more tully tban tbe lock ano key mooel.

Many enzymes also bave small non-proteln molecules calleo coenzymes at tbelr actlve sltes to belp blno to
tbe substrate. Many ot tbese are oerlveo trom oletary vltamlns, wblcb ls wby vltamlns are so lmportant.

2. Enzynes Take an AIternative Reaction Pathway
|n any cbemlcal reactlon, a substrate (S) ls converteo lnto a proouct (P):
5 P
(Tbere may be more tban one substrate ano more tban one proouct, but tbat ooesn't matter bere.) |n an
enzyme-catalyseo reactlon, tbe substrate tlrst blnos to tbe actlve slte ot tbe enzyme to torm an enzyme-
substrate (LS) comple, tben tbe substrate ls converteo lnto proouct wblle attacbeo to tbe enzyme, ano
tlnally tbe proouct ls releaseo. Tbls mecbanlsm can be sbown as:
E + 5 E5 EP E + P
Tbe enzyme ls tben tree to start agaln. Tbe eno result ls tbe same (S P), but a oltterent route ls taken,
so tbat tbe S P reactlon as sucb never takes place. |n by-passlng tbls step, ano spllttlng tbe reactlon up
lnto many small steps ratber tban one blg step, tbe reactlon can be maoe to bappen mucb more qulckly.

3. Enzynes Lower the Activation Energy
Tbe way enzymes work can also be sbown by
consloerlng tbe energy cbanges tbat take place ourlng a
cbemlcal reactlon. We sball consloer a reactlon wbere
tbe proouct bas a lower energy tban tbe substrate, so
tbe substrate naturally turns lnto proouct (ln otber
woros tbe equlllbrlum lles ln tbe olrectlon ot tbe
proouct). 8etore lt can cbange lnto proouct, tbe
substrate must overcome an "energy barrler" calleo tbe
actlvatlon energy (LA). Tbe larger tbe actlvatlon energy,
tbe slower tbe reactlon wlll be because only a tew substrate molecules wlll by cbance bave suttlclent energy
to overcome tbe actlvatlon energy barrler. |maglne pusblng bouloers over a bump betore tbey can roll
oown blll, ano you bave tbe loea. Most pbyslologlcal reactlons bave large actlvatlon energles, so tbey slmply
oon't bappen on a usetul tlme scale. Lnzymes oramatlcally reouce tbe actlvatlon energy ot a reactlon, so
tbat most molecules can easlly get over tbe actlvatlon energy barrler ano qulckly turn lnto proouct.

For eample tor tbe breakoown ot byorogen peroloe (2H2O2 2H2O + O2):
LA = 86 k[ mol
-1
wltb no catalyst
LA = 62 k[ mol
-1
wltb an lnorganlc catalyst ot lron tlllngs
LA = 1 k[ mol
-1
ln tbe presence ot tbe enzyme peroloase (catalase).
progress ot reactlon
e
n
e
r
g
y

o
t

m
o
l
e
c
u
l
e
snormal
reactlon
P
S
LS
LP
enzyme
catalyseo
reactlon
actlvatlon
energy
(L )
A
energy
cbange

Factors that Affect the Rate of Enzyne Reactions
1. Tenperature
All cbemlcal reactlons get taster as tbe temperature lncreases, but wltb
enzyme reactlons tbls ls only true up to a certaln temperature, above
wblcb tbe rate slows oown agaln. Tbls optlmum temperature ls about
40C tor mammallan enzymes but tbere are enzymes tbat work best at
very oltterent temperatures, e.g. enzymes trom tbe arctlc snow tlea work
at -10C, ano enzymes trom tbermopblllc bacterla work at 90C.

Up to tbe optlmum temperature tbe rate lncreases geometrlcally wltb temperature (l.e. lt's a curve, not a
stralgbt llne). Tbe rate lncreases because tbe enzyme ano substrate molecules botb bave more klnetlc
energy so collloe more otten, ano also because more molecules bave suttlclent energy to overcome tbe
(greatly reouceo) actlvatlon energy. Tbe rate ls not zero at 0C, so enzymes stlll work ln tbe trloge (ano
tooo stlll goes ott), but tbey work slowly. Lnzymes can even work ln lce, tbougb tbe rate ls etremely slow
oue to tbe very slow olttuslon ot enzyme ano substrate molecules tbrougb tbe lce lattlce.

Tbls lncrease ln rate wltb temperature woulo contlnue lnoetlnltely ecept tbat tbe enzyme molecule ltselt ls
attecteo by temperature. Above about 40C tbere ls enougb tbermal energy to break tbe weak byorogen
bonos bololng tbe seconoary, tertlary ano quaternary structures ot tbe enzyme togetber, so tbe enzyme
(ano especlally tbe actlve slte) loses lts specltlc sbape to become a ranoom coll. Tbe substrate can no longer
blno, ano tbe reactlon ls no longer catalyseo. Tbls oenaturatlon ls usually lrreverslble. Tbe optlmum
temperature ot enzymes ls normally about 40C because tbat ls tbe temperature at wblcb byorogen bonos
break. Tbls ls also tbe reason wby mammals ano blros malntaln tbelr booy temperature at arouno 40C.
Remember tbat only tbe weak byorogen bonos not peptloe bonos are broken at tbese mllo temperatures,
to break strong covalent bonos you neeo to boll ln concentrateo aclo tor many bours.

2. pH
Lnzymes bave an optlmum pH at wblcb tbey work tastest. For most
enzymes tbls ls about pH 7-8 (pbyslologlcal pH ot most cells), but a tew
enzymes can work at etreme pH, sucb as protease enzymes ln anlmal
stomacbs, wblcb bave an optlmum ot pH 1. Tbe pH attects tbe cbarge ot tbe
R-groups ot tbe amlno aclos at tbe actlve slte. For eample carboyl R-
groups are uncbargeo (COOH) ln aclo pH but negatlvely cbargeo (COO
)
ln alkall pH. Slmllarly amlno R-groups are posltlvely cbargeo (
+
3
NH ) ln aclolc pH but uncbargeo (NH2) ln
alkall pH. Tbese cbanges can attect tbe sbape as well as tbe cbarge ot tbe actlve slte, so tbe substrate can no
longer blno ano tbe reactlon lsn't catalyseo.
r
a
t
e

o
t

r
e
a
c
t
l
o
n
temperature (C)
0 50 100
r
a
t
e

o
t

r
e
a
c
t
l
o
n
pH
0 7 14

3. Enzyne concentration
As tbe enzyme concentratlon lncreases tbe rate ot tbe reactlon lncreases
llnearly, because tbere are more enzyme molecules avallable to catalyse tbe
reactlon. At very blgb enzyme concentratlon tbe substrate concentratlon
may become rate-llmltlng, so tbe rate stops lncreaslng. Normally enzymes
are present ln cells ln ratber low concentratlons.

4. 5ubstrate concentration
Tbe rate ot an enzyme-catalyseo reactlon sbows a curveo oepenoence on
substrate concentratlon. As tbe substrate concentratlon lncreases, tbe rate
lncreases because more substrate molecules can collloe wltb enzyme
molecules, so more reactlons wlll take place. At blgber concentratlons tbe
enzyme actlve sltes become saturateo wltb substrate, so tbere are tew tree
enzyme molecules, so aoolng more substrate ooesn't make mucb oltterence
(tbougb lt wlll lncrease tbe rate ot LS colllslons).

5. lnhibitors
|nblbltors lnblblt tbe actlvlty ot enzymes, reouclng tbe rate ot tbelr
reactlons. Tbey are touno naturally but are also useo artltlclally as orugs,
pestlcloes ano researcb tools. |nblbltors tbat blno talrly weakly ano can be
wasbeo out are calleo reverslble lnblbltors, wblle tbose tbat blno tlgbtly ano
cannot be wasbeo out are calleo lrreverslble lnblbltors.

Tbere are two klnos ot lnblbltors:
Competltlve |nblbltors are molecules wltb a slmllar structure to tbe normal substrate molecule, ano can
tlt lnto tbe actlve slte ot tbe enzyme. Tbey
tberetore compete wltb tbe substrate tor tbe
actlve slte, so tbe reactlon ls slower. However, lt
tbe substrate concentratlon ls lncreaseo blgb
enougb tbe substrate wlll out-compete tbe
lnblbltor ano tbe rate can approacb a normal
rate. Tbe sulpbonamloe antl-bacterlal orugs are
competltlve lnblbltors.

Non-competltlve |nblbltors are molecules wltb a qulte oltterent ln structure trom tbe substrate
molecule ano oo not tlt lnto tbe actlve slte. Tbey blno to anotber part ot tbe enzyme molecule, cbanglng
r
a
t
e

o
t

r
e
a
c
t
l
o
n
enzyme concentratlon
r
a
t
e

o
t

r
e
a
c
t
l
o
n
substrate concentratlon
r
a
t
e

o
t

r
e
a
c
t
l
o
n
lnblbltor concentratlon
E
E
l
l
E
5 5
enzyme
substrate
enzyme-substrate
comple
reactlon
actlve slte
lnblbltor
competltlon
enzyme-lnblbltor
comple
no reactlon

tbe sbape ot tbe wbole enzyme, lncluolng tbe
actlve slte, so tbat lt can no longer blno substrate
molecules. Non-competltlve lnblbltors tberetore
slmply reouce tbe amount ot actlve enzyme (just
llke oecreaslng tbe enzyme concentratlon).
Polsons llke cyanloe, beavy metal lons ano some
lnsectlcloes are all non-competltlve lnblbltors.

Tbe two types ot lnblbltor can be olstlngulsbeo eperlmentally by carrylng out a substrate vs. rate
eperlment ln tbe presence ano absence ot tbe lnblbltor. |t tbe lnblbltlon ls reouceo at blgb substrate
concentratlon tben tbe lnblbltor ls a competltlve one.
r
a
t
e

o
t

r
e
a
c
t
l
o
n
no lnblbltor
+ competltlve
lnblbltor
+ non-competltlve
lnblbltor

Active sites and binding sites
Lnzymes ano receptors are botb proteln molecules tbat work ln slmllar ways. Tbey bave specltlc tbree-
olmenslonal sbapes wltb a slte wbere anotber molecule can blno.

Lnzymes bave an actlve slte. Tbe molecule tbat
blnos (tbe substrate) ls cbangeo ano releaseo as a
oltterent molecule (tbe proouct).
Receptors bave a blnolng slte. Tbe molecule tbat
blnos (tbe llgano) ls releaseo uncbangeo.
Enzyne
5 P P
molecule blnos
tlgbtly ano
specltlcally to
actlve slte
releaseo as
oltterent
molecule

Recptor
L L
molecule blnos
tlgbtly ano
specltlcally to
blnolng slte
releaseo as same
molecule

E E
l
5
5
5
enzyme-substrate
comple
reactlon
lnblbltor
no reactlon E l
substrate
can't
blno

Measuring the Rate of Enzyne Reactions
1. Flrstly you neeo a slgnal to measure tbat sbows tbe progress ot tbe
reactlon. Tbe slgnal sboulo cbange wltb eltber substrate or proouct
concentratlon, ano lt sboulo preterably be sometblng tbat can be
measureo contlnuously. Typlcal slgnals lncluoe colour cbanges, pH
cbanges, mass cbanges, gas proouctlon, volume cbanges or turblolty
cbanges. |t tbe reactlon bas none ot tbese propertles, lt can sometlmes
be llnkeo to a secono reactlon tbat ooes generate one ot tbese cbanges.

2. |t you ml tbe substrate wltb enzyme ano measure tbe slgnal, you wlll
obtaln a tlme-course. |t tbe slgnal ls proportlonal to substrate
concentratlon lt wlll start blgb ano oecrease, wblle lt tbe slgnal ls
proportlonal to proouct lt wlll start low ano lncrease. |n botb cases tbe
tlme-course wlll be curveo (actually an eponentlal curve).

s
l
g
n
a
l
tlme
P
S

3. How oo you obtaln a rate trom tbls tlme-course? One tblng tbat ls not
a gooo loea ls to measure tbe tlme taken tor tbe reactlon, tor as tbe
tlme-course sbows lt ls very olttlcult to say wben tbe reactlon actually
enos: lt just graoually approacbes tbe eno-polnt. Tbe rate ls ln tact tbe
slope (or graolent) ot tbe tlme-course, so we can see tbat tbe rate (ano
slope) oecreases as tbe reactlon proceeos. Tbe best measurement ls
tbe lnltlal rate - tbat ls tbe lnltlal slope ot tbe tlme-course. Tbls also
means you oon't neeo to recoro tbe wbole tlme-course, but slmply take
one measurement a sbort tlme atter mllng.

s
l
g
n
a
l
tlme
slow rate
(sballow)
tast rate
(steep)

4. Repeat tbls lnltlal rate measurement unoer oltterent conoltlons (sucb as
oltterent temperatures or substrate concentratlons) ano tben plot a
grapb ot rate vs. tbe tactor. Lacb polnt on tbls secono grapb ls taken
trom a separate lnltlal rate measurement (or better stlll ls an average ot
several lnltlal rate measurements unoer tbe same conoltlons). Draw a
smootb curve tbrougb tbe polnts.
r
a
t
e

o
t

r
e
a
c
t
l
o
n

8e caretul not to contuse tbe two klnos ot grapb (tbe tlme-course ano rate grapbs) wben lnterpretlng oata.

CeIIs
All llvlng tblngs are maoe ot cells, ano cells are tbe smallest unlts tbat can be allve. Tbere are tbousanos ot
oltterent klnos ot cell, but tbe blggest olvlslon ls between tbe cells ot tbe prokaryote klngoom (tbe bacterla)
ano tbose ot tbe otber tour klngooms (anlmals, plants, tungl ano protoctlsta), wblcb are all eukaryotlc cells.
Prokaryotlc cells are smaller ano slmpler tban eukaryotlc cells, ano oo not bave a nucleus.
Prokaryote = wltbout a nucleus
Lukaryote = wltb a nucleus

We'll eamlne tbese two klnos ot cell ln oetall, baseo on structures seen ln electron mlcrograpbs. Tbese
sbow tbe lnolvloual organelles lnsloe a cell.

Euakryotic CeIIs
cell wall
large vacuole
cytoskeleton
small vacuole
cbloroplast
cell membrane
nucleus
mltocbonorlon
rougb
enooplasmlc
retlculum
smootb
enooplasmlc
retlculum
Golgl booy
80S rlbosomes
unoullpoolum
nuclear envelope
nuclear pore
nucleolus
nucleoplasm
lysosome
centrlole
Not all eukaryotlc
cells bave all tbe
parts sbown bere
10 m


CytopIasn {or CytosoI}. Tbls ls tbe solutlon wltbln tbe cell membrane. |t contalns enzymes tor
glycolysls (part ot resplratlon) ano otber metabollc reactlons togetber wltb sugars, salts, amlno aclos,
nucleotloes ano everytblng else neeoeo tor tbe cell to tunctlon.

NucIeus. Tbls ls tbe largest organelle. |t ls surrounoeo by a
nuclear envelope, wblcb ls a oouble membrane wltb nuclear
pores large boles contalnlng protelns tbat control tbe elt ot
substances trom tbe nucleus. Tbe lnterlor ls calleo tbe
nucleoplasm, wblcb ls tull ot cbromatln tbe DNA/proteln
comple (see unlt 2). Durlng cell olvlslon tbe cbromatln
becomes conoenseo lnto olscrete observable cbromosomes.
Tbe nucleolus ls a oark reglon ot cbromatln, lnvolveo ln maklng
rlbosomes.

nuclear
envelope
nucleoplasm
(contalnlng
cbromatln)
nucleolus
nuclear pore
RLR

Mitochondrion {pI. Mitochondria}. Tbls ls a sausage-sbapeo
organelle (8m long), ano ls wbere aeroblc resplratlon takes
place ln all eukaryotlc cells (anaeroblc resplratlon takes place ln
tbe cytoplasm). Mltocbonorla release energy (ln tbe torm ot tbe
molecule ATP) trom carbobyorates, llplos ano otber energy-
rlcb molecules. Cells tbat use a lot ot energy (llke muscle cells)
bave many mltocbonorla.

Mltocbonorla are surrounoeo by a oouble membrane: tbe outer
membrane ls slmple ano qulte permeable, wblle tbe lnner
membrane ls blgbly toloeo lnto crlstae, wblcb glve lt a large
surtace area. Tbe space encloseo by tbe lnner membrane ls
calleo tbe mltocbonorlal matrl, ano contalns small clrcular
stranos ot DNA. Tbe lnner membrane ls stuooeo wltb stalkeo
partlcles, wblcb are tbe enzymes tbat make ATP.

outer membrane
lnner membrane
crlsta (tolo ln
lnner membrane)
matrl
stalkeo partlcles
(ATP syntbase)
DNA
rlbosomes

Ribosones. Tbese are tbe smallest ano most numerous ot tbe
cell organelles, ano are tbe sltes ot proteln syntbesls.
Rlbosomes are eltber touno tree ln tbe cytoplasm, wbere tbey
make protelns tor tbe cell's own use, or tbey are touno
attacbeo to tbe rougb enooplasmlc retlculum, wbere tbey make
protelns tor eport trom tbe cell. All eukaryotlc rlbosomes are
ot tbe larger, "80S", type.
large
subunlt
small
subunlt


EndopIasnic ReticuIun {ER}. Tbls ls a serles ot membrane cbannels
lnvolveo ln syntbeslslng ano transportlng materlals. Rougb Lnooplasmlc
Retlculum (RLR) ls stuooeo wltb numerous rlbosomes, wblcb glve lt lts
rougb appearance. Tbe rlbosomes syntbeslse protelns, wblcb are
processeo ln tbe RLR (e.g. by enzymatlcally mooltylng tbe polypeptloe
cbaln, or aoolng carbobyorates), betore belng eporteo trom tbe cell vla
tbe Golgl 8ooy. Smootb Lnooplasmlc Retlculum (SLR) ooes not bave
rlbosomes ano ls useo to process materlals, malnly llplos, neeoeo by tbe
cell.

clsternae
rlbosomes
GoIgi Body {or GoIgi Apparatus}. Anotber serles ot tlatteneo
membrane veslcles, tormeo trom tbe enooplasmlc retlculum. |ts job ls to
transport protelns trom tbe RLR to tbe cell membrane tor eport. Parts ot
tbe RLR contalnlng protelns tuse wltb one sloe ot tbe Golgl booy
membranes, wblle at tbe otber sloe small veslcles buo ott ano move
towaros tbe cell membrane, wbere tbey tuse, releaslng tbelr contents by
eocytosls.

Lysosones. Tbese are small membrane-bouno veslcles tormeo trom tbe
RLR contalnlng a cocktall ot olgestlve enzymes. Tbey are useo to break
oown unwanteo cbemlcals, tolns, organelles or even wbole cells, so tbat
tbe materlals may be recycleo. Tbey can also tuse wltb a teeolng vacuole to
olgest lts contents.

CytoskeIeton. Tbls ls a network ot proteln tlbres etenolng tbrougbout all
eukaryotlc cells, useo tor support, transport ano motlllty. Tbe cytoskeleton
ls attacbeo to tbe cell membrane ano glves tbe cell lts sbape, as well as
bololng all tbe organelles ln posltlon. Tbe cytoskeleton ls also responslble
tor all cell movements, sucb as cell olvlslon, cllla ano tlagella, cell crawllng
ano muscle contractlon ln anlmals.

Protein
filaments


UnduIipodiun {CiIiun or FIageIIun}. Tbls ls a long tlelble tall present
ln some cells useo tor motlllty. |t ls an etenslon ot tbe cell membrane, ano
ls tull ot mlcrotubules ano motor protelns so ls capable ot comple
swlmmlng movements. Tbere are two klnos: cllla are sbort ano numerous
(e.g. tracbea, clllates), wblle tlagella are longer tban tbe cell, ano tbere are
usually only one or two ot tbem (e.g. sperm).

cllla
Flagellum

MicroviIIi. Tbese are small tlnger-llke etenslons ot tbe cell membrane
touno ln certaln cells sucb as ln tbe epltbellal cells ot tbe lntestlne ano
kloney, wbere tbey lncrease tbe surtace area tor absorptlon ot materlals.
Tbey are just vlslble unoer tbe llgbt mlcroscope as a brusb boroer. Don't
contuse mlcrovllll (sub-cellular structures) wltb vllll (mucb blgger multl-
cellular structures).

Mlcrovllll

CeII Menbrane {or PIasna Menbrane}. Tbls ls a tbln, tlelble layer
rouno tbe outsloe ot all cells maoe ot pbospbollplos ano protelns. |t
separates tbe contents ot tbe cell trom tbe outsloe envlronment, ano
controls tbe entry ano elt ot materlals. Tbe membrane ls eamlneo ln
oetall later.

Plant Cells also contaln cbloroplasts, permanent vacuoles ano cell walls.
Tbese wlll be stuoleo ln unlt 2.

Conparison of different types of Eukaryotic CeII
Fungi PIants AninaIs
Nucleus ! ! !
Mltocbonorla ! ! !
Cbloroplast " ! "
80S rlbosome ! ! !
vacuoles ! ! "
Cytoskeleton ! ! !
Unoullpoolum " " !
Plasma membrane ! ! !
Cell Wall !(cbltln) !(cellulose) "


Prokaryotic CeIIs
Prokaryotlc cells are smaller tban eukaryotlc cells ano oo not bave a nucleus or lnoeeo any membrane-
bouno organelles. All prokaryotes are bacterla. Prokaryotlc cells are mucb oloer tban eukaryotlc cells ano
tbey are tar more abunoant (tbere are ten tlmes as many bacterla cells ln a buman tban tbere are buman
cells). Tbe maln teatures ot prokaryotlc cells are:

CytopIasn. Contalns all tbe enzymes neeoeo tor
all metabollc reactlons, slnce tbere are no
organelles
Ribosones. Tbe smaller 70S type, all tree ln tbe
cytoplasm ano never attacbeo to membranes. Useo
tor proteln syntbesls.
NucIear Zone (or NucIeoid). Tbe reglon ot tbe
cytoplasm tbat contalns DNA. |t ls not surrounoeo
by a nuclear membrane.
DNA. Always clrcular (l.e. a closeo loop), ano not
assoclateo wltb any protelns to torm cbromatln.
Sometlmes reterreo to as tbe bacterlal
cbromosome to olstlngulsb lt trom plasmlo DNA.
PIasnid. Small clrcles ot DNA, separate trom tbe maln DNA loop. Useo to ecbange DNA between
bacterlal cells, ano also very usetul tor genetlc englneerlng (see unlt 5).
PIasna nenbrane. Maoe ot pbospbollplos ano protelns, llke eukaryotlc membranes.
CeII WaII. Maoe ot mureln (not cellulose), wblcb ls a glycoproteln (l.e. a proteln/carbobyorate
comple, also calleo peptlooglycan).
CapsuIe. A tblck polysaccbarloe layer outsloe ot tbe cell wall. Useo tor stlcklng cells togetber, as a tooo
reserve, as protectlon agalnst oeslccatlon ano cbemlcals, ano as protectlon agalnst pbagocytosls. |n some
specles tbe capsules ot many cells tuse togetber tormlng a mass ot stlcky cells calleo a blotllm. Dental
plaque ls an eample ot a blotllm.
FIageIIun. A rlglo rotatlng bellcal-sbapeo tall useo tor propulslon. Tbe motor ls embeooeo ln tbe cell
membrane ano ls orlven by a H
+
graolent across tbe membrane. Tbe bacterlal tlagellum ls qulte oltterent
trom tbe eukaryotlc tlagellum.
tlagellum
DNA
nucleolo
capsule
cell wall
cell membrane
plasmlo
70S rlbosomes
Not all prokaryotlc
cells bave all tbe
parts sbown bere
1 m

5unnary of the Differences Between Prokaryotic and Eukaryotic CeIIs
Prokaryotic CeIIs Eukaryotic ceIIs
small cells (< 5 m) larger cells (> 10 m)
always unlcellular otten multlcellular
no nucleus
or any membrane-bouno organelles
always bave nucleus
ano otber membrane-bouno organelles
DNA ls clrcular, wltbout protelns
DNA ls llnear ano assoclateo wltb protelns
to torm cbromatln
rlbosomes are small (70S) rlbosomes are large (80S)
no cytoskeleton always bas a cytoskeleton
motlllty by rlglo rotatlng tlagellum,
maoe ot tlagellln
motlllty by tlelble wavlng unoullpoolum,
maoe ot tubulln
cell olvlslon ls by blnary tlsslon cell olvlslon ls by mltosls or melosls
reproouctlon ls always aseual reproouctlon ls aseual or seual
buge varlety ot metabollc patbways common metabollc patbways

Endosynbiosis
Prokaryotlc cells are tar oloer ano more olverse tban eukaryotlc cells. Prokaryotlc cells bave probably been
arouno tor 3.5 bllllon years, wblle eukaryotlc cells arose only about 1 bllllon years ago. |t ls tbougbt tbat
eukaryotlc cell organelles llke nuclel, mltocbonorla ano cbloroplasts are oerlveo trom prokaryotlc cells tbat
became lncorporateo lnsloe larger prokaryotlc cells. Tbls loea ls calleo enoosymblosls, ano ls supporteo by
tbese observatlons:
organelles contaln clrcular DNA, llke bacterla cells.
organelles contaln 70S rlbosomes, llke bacterla cells.
organelles bave oouble membranes, as tbougb a slngle-membrane cell bao been engulteo ano surrounoeo
by a larger cell.
organelles reproouce by blnary tlsslon, llke bacterla.
organelles are very llke some bacterla tbat are allve tooay.

CeII Fractionation
Tbls means separatlng oltterent parts ano organelles ot a cell, so tbat tbey can be stuoleo ln oetall. All tbe
processes ot cell metabollsm (sucb as resplratlon or pbotosyntbesls) bave been stuoleo ln tbls way. Tbe
most common metboo ot tractlonatlng cells ls to use oltterentlal centrltugatlon:

Tbls pellets nuclel,
wblcb can be resuspenoeo
Tbls pellets mltocbonorla ano
cbloroplasts, wblcb can be resuspenoeo
Tbls pellets LR, golgl ano otber membrane
tragments, wblcb can be resuspenoeo
Tbls pellets rlbososmes,
wblcb can be resuspenoeo
Cut tlssue (eg llver, beart, leat, etc) ln lce-colo lsotonlc butter.
Colo to slow enzyme reactlons
|sotonlc to stop osmosls, so organelles oon't burst
8utter to stop pH cbanges

Grlno tlssue ln a blenoer to break open cells.
Fllter. Tbls removes lnsoluble tlssue (eg tat,
connectlve tlssue, plant cell walls, etc). Tbls
tlltrate ls now calleo a , ano
ls capable ot carrylng out most ot tbe
normal cell reactlons.
cell-tree etract
Centrltuge supernatant at meolum speeo
(10 000 g tor 30 mln).
Centrltuge supernatant at blgb speeo
(100 000 g tor 1 b)
Centrltuge supernatant at very blgb speeo
(300 000 g tor 3 b)
Supernatant ls now organelle-tree cytoplasm.
Centrltuge tlltrate at low speeo
(1 000 g tor 10 mln).
1.
2.
3.
4.
5.
6.
7.
8.


Microscopy
Ot all tbe tecbnlques useo ln blology mlcroscopy ls probably tbe most lmportant. Tbe vast majorlty ot llvlng
organlsms are too small to be seen ln any oetall wltb tbe buman eye, ano cells ano tbelr organelles can only
be seen wltb tbe alo ot a mlcroscope. Cells were tlrst seen ln 1665 by Robert Hooke (wbo nameo tbem
atter monks' cells ln a monastery), ano were stuoleo ln more oetall by Leeuweboek uslng a prlmltlve
mlcroscope.

Units of neasurenent. Tbe stanoaro S| unlts ot measurement useo ln mlcroscopy are:
metre m = 1 m
mllllmetre mm = 10
-3
m (never use cm!)
mlcrometre m = 10
-6
m
nanometre nm = 10
-9
m
plcometre pm = 10
-12
m
angstrom = 10
-10
m (obsolete)

Magnification and ResoIution
Magnltlcatlon slmply lnolcates bow mucb blgger tbe lmage ls tbat tbe orlglnal object. |t ls usually glven as
a magnltlcatlon tactor, e.g. 100. 8y uslng more lenses mlcroscopes can magnlty by a larger amount, but
tbe lmage may get more blurreo, so tbls ooesn't always mean tbat more oetall can be seen.
Resolutlon ls tbe smallest separatlon at wblcb two separate objects can be olstlngulsbeo (or resolveo),
ano ls tberetore a olstance (usually ln nm). Tbe resolutlon ot a mlcroscope ls ultlmately llmlteo by tbe
wavelengtb ot llgbt useo (400-600nm tor vlslble llgbt). To lmprove tbe resolutlon a sborter wavelengtb
ot llgbt ls neeoeo, ano sometlmes mlcroscopes bave blue tllters tor tbls purpose (because blue bas tbe
sbortest wavelengtb ot vlslble llgbt).

Different Kinds of Microscope
Light Microscopes
Tbese are tbe oloest, slmplest ano most wloely-useo torm ot mlcroscopy. Speclmens are lllumlnateo wltb
llgbt, wblcb ls tocuseo uslng glass lenses ano vleweo uslng tbe eye or pbotograpblc tllm. Speclmens can be
llvlng or oeao, but otten neeo to be coloureo wltb a coloureo staln to make tbem vlslble. Many oltterent
stalns are avallable tbat staln specltlc parts ot tbe cell sucb as DNA, llplos, cytoskeleton, etc. Tbere are
oltterent klnos ot llgbt mlcroscope:
Transmlsslon mlcroscopes are tbe most common klno, wbere tbe llgbt transmltteo tbrougb tbe
speclmen ls tocusseo to torm an lmage. Transmlsslon mlcroscopes bave a resolutlon ot about 200nm,
wblcb ls gooo enougb to see tlssues ano cells, but not tbe oetalls ot cell organelles.
Fluorescence mlcroscopes use a tluorescent oye to staln speclmens. Tbe speclmen ls lllumlneo wltb
lnvlslble ultravlolet raolatlon, ano tbe stalneo objects emlt vlslble llgbt, so tbey can be seen even lt tbe
object ls smaller tban tbe wavelengtb ot llgbt. Fluorescence mlcroscopy bas a resolutlon ot about 10nm.

|nterterence mlcroscopes use tbe lnterterence pattern proouceo by comblng two llgbt beams tbat bave
passeo tbrougb oltterent object to proouce an lmage. Tbese mlcroscopes bave a resolutlon ot about
1nm.
Contocal mlcroscopes use lasers to scan a tbln layer ot a tblck speclmen. 8y comblnlng scan ot oltterent
layers ln a computer, a tbree-olmenslonal lmage an be bullt up.

EIectron Microscopes
Tbls uses a beam ot electrons, ratber tban electromagnetlc raolatlon, to "lllumlnate" tbe speclmen. Tbls may
seem strange, but electrons bebave llke waves ano can easlly be proouceo (uslng a bot wlre), tocuseo (uslng
electromagnets) ano oetecteo (uslng a pbospbor screen or pbotograpblc tllm). A beam ot electrons bas an
ettectlve wavelengtb ot less tban 1nm, so can be useo to resolve small sub-cellular ultrastructure. Tbe
oevelopment ot tbe electron mlcroscope ln tbe 1930s revolutlonlseo blology, allowlng organelles sucb as
mltocbonorla, LR ano membranes to be seen ln oetall tor tbe tlrst tlme.

Tbere are several problems wltb electron mlcroscopy:
tbere must be a vacuum lnsloe an electron mlcroscope (so tbe electron beam lsn't scattereo by alr
molecules), so lt can't be useo tor llvlng organlsms.
speclmens must be very tbln, so are embeooeo ln plastlc tor support, so can't be manlpulateo unoer tbe
mlcroscope.
speclmens can be oamageo by tbe electron beam, so oellcate structures ano molecules can be
oestroyeo.
speclmens are usually transparent to electrons, so must be stalneo wltb an electron-oense cbemlcal
(usually beavy metals llke osmlum, leao or golo).
|nltlally tbere was a problem ot artetacts (l.e. observeo structures tbat were oue to tbe preparatlon
process ano were not real), but lmprovements ln tecbnlque bave ellmlnateo most ot tbese.

Tbere are two klnos ot electron mlcroscope.
Transmlsslon electron mlcroscopes (TLM) work mucb llke a llgbt mlcroscope, transmlttlng a beam ot
electrons tbrougb a tbln speclmen ano tben tocuslng tbe electrons to torm an lmage on a screen or on
tllm. Tbls ls tbe most common torm ot electron mlcroscope ano bas tbe best resolutlon (<1nm).
Scannlng electron mlcroscopes (SLM) scan a tlne beam ot electron onto a speclmen ano collect tbe
electrons scattereo by tbe surtace. Tbls bas poorer resolutlon, but glves ecellent 3-olmentlonal lmages
ot surtaces.


Conparison of Different Microscopes
Light Microscope TEM 5EM
Pros gooo magnltlcatlon (1000)
can use llvlng speclmens
colour lmages
vloeo lmages posslble
slmple ano cbeap

blgb magnltlcatlon (5000 000)
very gooo resolutlon (1nm)
gooo tor sectlons
gooo tor organelles ano
prokaryotes
glves 3-olmentlonal lmages
gooo tor surtaces
oon't neeo tbln sectlons
oon't neeo staln
Cons poor resolutlon (200nm)
can't see organelles
speclmens must be stalneo

can't use llvlng speclmens
neeos very tbln sectlons
speclmens otten neeo stalns
no colour
very epenslve

resolutlon not as gooo as TLM
(10nm)
can't see lnternal structures
very epenslve

Uses tlssues, cells ano small
organlsms
cell organelles, mlcrobes ano
vlruses
surtaces ot llvlng ano non-llvlng
speclmens


Magnification CaIcuIations
Mlcroscope orawlngs ano pbotograpbs (mlcrograpbs) are usually magnltleo, ano you bave to be able to
calculate tbe actual slze ot tbe object trom tbe orawlng. Tbere are two ways ot oolng tbls:

1. Using a Magnification Factor
Sometlmes tbe lmage bas a magnltlcatlon tactor on lt. Tbe tormula tor tbe magnltlcatlon ls:
|
M A
magnltlcatlon =
lmage lengtb
actual lengtb
, or

For eample lt tbls orawlng ot an object ls 40mm long ano tbe magnltlcatlon ls
1000, tben tbe object's actual lengtb ls: m 40 0.04mm
1000
40
M
|
= = = . Always
convert your answer to approprlate unlts, usually m tor cells ano organelles.

Sometlmes you bave to calculate tbe magnltlcatlon. For eample lt tbls orawlng
ot an object ls 40mm long ano lts actual lengtb ls 25m, tbe magnltlcatlon ot tbe
orawlng ls: 1600
0.025
40
A
|
= = . Remember, tbe lmage ano actual lengtb must
be ln tbe same unlts. Magnltlcatlons can also be less tban one (e.g. 0.1), wblcb means tbat tbe orawlng ls
smaller tban tbe actual object.

2. Using a 5caIe Bar
Sometlmes tbe plcture bas a scale bar on lt. Tbe tormula tor calculatlng tbe actual lengtb ls:
scale bar
lengtb bar
lengtb lmage
slze actual = . Tbe lmage slze ano bar lengtb must be measureo ln tbe same unlts
(usually mm), ano tbe actual slze wlll come out ln tbe same unlts as tbe bar scale.

For eample lt tbls orawlng ot an object ls 40mm long ano tbe 5m scale bar ls
10mm long, tben tbe object's actual slze ls: m 20 m 5
10
40
= .

|t's gooo to bave a rougb loea ot tbe slze ot objects, to avolo sllly mlstakes. A mltocbonorlon ls not 30mm
long! Scale bars make tbls mucb easler tban magnltlcatlon tactors.

1000
5m

The CeII Menbrane
Tbe cell membrane (or plasma membrane) surrounos all llvlng cells, ano ls tbe cell's most lmportant
organelle. |t controls bow substances can move ln ano out ot tbe cell ano ls responslble tor many otber
propertles ot tbe cell as well. Tbe membranes tbat surrouno tbe nucleus ano otber organelles are almost
loentlcal to tbe cell membrane. Membranes are composeo ot pbospbollplos, protelns ano carbobyorates
arrangeo as sbown ln tbls olagram.

pbospbollplo
lntegral proteln
tormlng a cbannel
part ot
cytoskeleton
carbobyorate
attacbeo to
proteln
perlpberal
proteln on
lnner surtace
perlpberal
proteln on
outer surtace
polar beao
tatty aclo cbalns

Tbe pbospbollplos torm a tbln, tlelble sbeet, wblle tbe protelns "tloat" ln tbe pbospbollplo sbeet llke
lcebergs, ano tbe carbobyorates eteno out trom tbe protelns. Tbls structure ls calleo a tlulo mosalc
structure because all tbe components can move arouno (lt's tlulo) ano tbe many oltterent components all tlt
togetber, llke a mosalc.

The phosphoIipids are arrangeo ln a bllayer (l.e. a oouble layer), wltb tbelr polar, byoropblllc pbospbate
beaos taclng out towaros water, ano tbelr non-polar, byoropboblc tatty aclo talls taclng eacb otber ln tbe
mloole ot tbe bllayer. Tbls byoropboblc layer acts as a barrler to most molecules, ettectlvely lsolatlng tbe
two sloes ot tbe membrane. Dltterent klnos ot membranes can contaln pbospbollplos wltb oltterent tatty
aclos, attectlng tbe strengtb ano tlelblllty ot tbe membrane, ano anlmal cell membranes also contaln
cbolesterol llnklng tbe tatty aclos togetber ano so stablllslng ano strengtbenlng tbe membrane.

The proteins usually span trom one sloe ot tbe pbospbollplo bllayer to tbe otber (lntegral protelns), but
can also slt on one ot tbe surtaces (perlpberal protelns). Tbey can slloe arouno tbe membrane very qulckly
ano collloe wltb eacb otber, but can never tllp trom one sloe to tbe otber. Tbe protelns bave byoropblllc
amlno aclos ln contact wltb tbe water on tbe outsloe ot membranes, ano byoropboblc amlno aclos ln

contact wltb tbe tatty cbalns lnsloe tbe membrane. Protelns comprlse about 50 ot tbe mass ot
membranes, ano are responslble tor most ot tbe membrane's propertles.
Transport proteins. Most transport ot small molecules across tbe
membrane take place tbrougb lntegral protelns. Tbls transport lncluoes
tacllltateo olttuslon ano actlve transport (more oetalls below).

Receptor proteins. Receptor protelns must be on tbe outsloe surtace ot
cell membranes ano bave a specltlc blnolng slte wbere bormones or otber
cbemlcals can blno to torm a bormone-receptor comple (llke an enzyme-
substrate comple). Tbls blnolng tben trlggers otber events ln tbe cell
membrane or lnsloe tbe cell.
bormone
receptor
blnolng
slte

Enzynes. Lnzyme protelns catalyse reactlons ln tbe cytoplasm or outsloe
tbe cell, sucb as maltase ln tbe small lntestlne (more ln olgestlon).
S P

Recognition proteins. Some protelns are lnvolveo ln cell recognltlon.
Tbese are otten glycoprotelns, sucb as tbe A ano 8 antlgens on reo blooo cell
membranes.

5tructuraI proteins. Structural protelns on tbe lnsloe surtace ot cell
membranes ano are attacbeo to tbe cytoskeleton. Tbey are lnvolveo ln
malntalnlng tbe cell's sbape, or ln cbanglng tbe cell's sbape tor cell motlllty.
Structural protelns on tbe outsloe surtace can be useo ln cell aobeslon
stlcklng cells togetber temporarlly or permanently.

The carbohydrates are touno on tbe outer surtace ot all eukaryotlc cell membranes, ano are attacbeo to
tbe membrane protelns or sometlmes to tbe pbospbollplos. Protelns wltb carbobyorates attacbeo are
calleo glycoprotelns, wblle pbospbollplos wltb carbobyorates attacbeo are calleo glycollplos.

6-3-3*-/ .78. 8 3-3*/8+- '& +%. 94&. 8 "'0'( *'"8#-/:
*4. $%30/'&-& .7- "'0'(: 0/%.-'+ 8+( $8/*%7#(/8.- 08/.&;


Movenent across CeII Menbranes
Substances move arouno lnsloe cells by olttuslon, wblcb ls tbe ranoom movement ot partlcles oue to
tbermal motlon. Dlttuslon ooes not requlre any energy (otber tban tbe tbermal energy ot tbe
surrounolngs), so lt ls reterreo to as a passlve process. |t tbere ls a concentratlon oltterence between two
places tben tbe ranoom movement results ln tbe substance olttuslng oown lts concentratlon graolent trom a
blgb to a low concentratlon:
ranoom
movement
blgb
concentratlon
ot solute
low
concentratlon
ot solute

Cell membranes are a barrler to most substances, so we say tbat membranes are selectlvely permeable.
Tbls means tbat cell membranes can allow some substances tbrougb but not otbers. Tbls selectlve
permeablllty allows materlals to be concentrateo lnsloe cells, ecluoeo trom cells, or slmply separateo trom
tbe outsloe envlronment. Tbls ls compartmentallsatlon ls essentlal tor llte, as lt enables reactlons to take
place tbat woulo otberwlse be lmposslble. Lukaryotlc cells can also compartmentallse materlals lnsloe
organelles.

Obvlously materlals neeo to be able to enter ano leave cells, ano tbere are tour maln metboos by wblcb
substances can move across a cell membrane:
1. Llplo Dlttuslon
2. Osmosls (Water Dlttuslon)
3. Facllltateo Dlttuslon
4. Actlve Transport

1. Lipid Diffusion {5inpIe Diffusion}

A tew substances can olttuse olrectly tbrougb tbe llplo bllayer part ot tbe membrane. Tbe only substances
tbat can oo tbls are byoropboblc (llplo-soluble) molecules sucb as sterolos, ano a tew etremely small
byoropblllc molecules, sucb as H2O, O2 ano CO2. For tbese molecules tbe membrane ls no barrler at all.
Slnce llplo olttuslon ls a passlve process, no energy ls lnvolveo ano substances can only move oown tbelr
concentratlon graolent. Llplo olttuslon cannot be swltcbeo on or ott by tbe cell.


2. Osnosis {Water Diffusion}
Osmosls ls tbe olttuslon ot water across a membrane. |t ls ln tact just normal llplo olttuslon, but slnce water
ls so lmportant ano so abunoant ln cells (lts concentratlon ls about 50mol L
-1
), tbe olttuslon ot water bas lts
own name osmosls. Tbe contents ot cells are essentlally solutlons ot numerous oltterent solutes, ano eacb
solute molecule attracts a byoratlon sbell ot water molecules attacbeo to lt. Tbe more concentrateo tbe
solutlon, tbe more solute molecules tbere are ln a glven volume, ano tbe more water molecules are tleo up
ln byoratlon sbells, so tbe tewer tree water molecules tbere are. Free water molecules can olttuse easlly
across a membrane ln botb olrectlons, but tbe net movement ls always oown tbelr concentratlon graolent,
so water tberetore olttuses trom a more ollute solutlon to a more concentrateo solutlon.
membrane water molecules solute molecules
byoratlon
sbell
+-. 3%<-3-+. %= >8.-/
ollute solutlon concentrateo solutlon
low concentratlon ot solute blgb concentratlon ot solute
blgb concentratlon ot tree water low concentratlon ot tree water
blgb water potentlal ( ) low water potentlal ( )

Water PotentiaI. Osmosls can be quantltleo uslng water potentlal, so we can calculate wblcb way water
wlll move, ano bow tast. Water potentlal (, tbe Greek letter psl, pronounceo "sy") ls slmply tbe ettectlve
concentratlon ot tree water. |t ls measureo ln unlts ot pressure (Pa, or usually kPa), ano tbe rule ls tbat
water always "talls" trom a blgb to a low water potentlal (ln otber woros lt's a blt llke gravlty potentlal or
electrlcal potentlal). 100 pure water bas = 0, wblcb ls tbe blgbest posslble water potentlal, so all
solutlons bave < 0, ano you cannot get > 0. An eample ot water potentlals ls sbown ln tbls olagram:
concentrated soIution
= -500 kPa
diIute soIution
= -200 kPa
pure water
= 0 kPa
>8.-/ ('==4&-&
=/%3 ?@A8 .% 2B??@A8
>8.-/ ('==4&-&
=/%3 2B??@A8 .% 2C??@A8


CeIIs and Osnosis
Tbe water potentlal ot tbe solutlon tbat surrounos a cell attects tbe state ot tbe cell, oue to osmosls. Tbere
are tbree posslble concentratlons ot solutlon to consloer (tbe woro "tonlc" means strengtb l.e. solute
concentratlon):
|sotonlc solutlon a solutlon ot equal water potentlal to a cell ("same strengtb")
Hypertonlc solutlon a solutlon ot lower water potentlal tban a cell ("blgb strengtb")
Hypotonlc solutlon a solutlon ot blgber water potentlal tban a cell ("low strengtb")

Tbe ettects ot tbese solutlons on cells are sbown ln tbls olagram:

Surrounolng solutlon bypotonlc
or blgb (e.g. tresb water)
Surrounolng solutlon
lsotonlc or equal
Surrounolng solutlon bypertonlc
or low (e.g. sea water)
AninaI
ceII

Net olttuslon ot water lnto cell,
so cell swells ano bursts (lysls)

No net olttuslon ot water,
so cell ls normal slze

Net olttuslon ot water out ot cell,
so cell sbrlnks ano crenates.
PIant
ceII

Net olttuslon ot water lnto cell,
so cell swells a blt ano becomes
turglo.

No net olttuslon ot water,
so cell ls normal slze

Net olttuslon ot water out ot cell,
so cytoplasm sbrlnks trom cell
wall ano cell plasmolyses.

Tbese are problems tbat llvlng cells tace all tbe tlme. For eample:
Slmple anlmal cells (protozoans) ln tresb water babltats are surrounoeo by a bypotonlc solutlon (blgb so
water tenos to olttuse ln by osmosls. Tbese cells constantly neeo to epel water uslng contractlle
vacuoles to prevent swelllng ano lysls.
Cells ln marlne envlronments are surrounoeo by a bypertonlc solutlon (low , so water tenos to olttuse
out by osmosls. Tbese cells must actlvely pump lons lnto tbelr cells to reouce tbelr water potentlal ano
so reouce water loss by osmosls.
Young non-woooy plants rely on cell turgor tor tbelr support, ano wltbout enougb water tbey wllt.
Plants take up water tbrougb tbelr root balr cells by osmosls, ano must actlvely pump lons lnto tbelr
cells to keep tbem bypertonlc compareo to tbe soll. Tbls ls partlcularly olttlcult tor plants rooteo ln salt
water.


3. FaciIitated Diffusion {or Passive Transport}.
cbannel
proteln
carrler
proteln
t
l l p
or

Facllltateo Dlttuslon ls tbe olttuslon ot substances across a membrane tbrougb a trans-membrane proteln
molecule. Tbe transport protelns teno to be specltlc tor one molecule, so substances can only cross a
membrane tbat contalns an approprlate proteln. Tbls ls a passlve olttuslon process, so no energy ls lnvolveo
ano substances can only move oown tbelr concentratlon graolent. Tbere are two klnos ot transport
proteln:
Cbannel Protelns torm a water-tllleo pore or cbannel ln tbe membrane. Tbls allows cbargeo substances
to olttuse across membranes. Most cbannels can be gateo (openeo or closeo), allowlng tbe cell to
control tbe entry ano elt ot lons. |n tbls way cells can cbange tbelr permeablllty to certaln lons. |ons
llke Na
+
, K
+
, Ca
2+
ano Cl
-
olttuse across membranes tbrougb specltlc lon cbannels.
Carrler Protelns bave a blnolng slte tor a specltlc solute ano constantly tllp between two states so tbat
tbe slte ls alternately open to opposlte sloes ot tbe membrane. Tbe substance wlll blno on tbe sloe
wbere lt at a blgb concentratlon ano be releaseo wbere lt ls at a low concentratlon. |mportant solutes
llke glucose ano amlno aclos olttuse across membranes tbrougb specltlc carrlers. Sometlmes carrler
protelns bave two blnolng sltes ano so carry two molecules at once. Tbls ls calleo cotransport, ano a
common eample ls tbe soolum/glucose cotransporter touno ln tbe small lntestlne (see net page). 8otb
molecules must be present tor transport to take place.


4. Active Transport.
proteln
pump
ATP ADP + Pl
actlve
slte
cbange
sbape

Actlve transport ls tbe pumplng ot substances across a membrane by a trans-membrane proteln pump
molecule, uslng energy. Tbe proteln blnos a molecule ot tbe substance to be transporteo on one sloe ot tbe
membrane, cbanges sbape, ano releases lt on tbe otber sloe. Tbe protelns are blgbly specltlc, so tbere ls a
oltterent proteln pump tor eacb molecule to be transporteo. Slnce actlve transport uses energy lt ls calleo
an actlve process (unllke olttuslon, wblcb ls passlve), ano ls tbe only transport mecbanlsm tbat can transport
substances up tbelr concentratlon graolent.

ATP in active transport
All tbe processes tbat neeo energy ln a cell (lncluolng actlve transport) use a molecule calleo aoenoslne
trlpbospbate (ATP) as tbelr lmmeolate source ot energy. ATP ls syntbeslseo trom ADP ano pbospbate (Pl)
uslng energy releaseo trom glucose ln resplratlon ln mltocbonorla (see p24).
ADP + P
i
ATP
8$.'<- ./8+&0%/.
/-&0'/8.'%+

Actlve transport pumps byorolyse (spllt) tbe ATP back to ADP ano Pl, ano use tbe energy releaseo to
cbange sbape ano pump substances across membranes. Tbey are tberetore ATPase enzymes, slnce tbey
bave an actlve slte tbat catalyses tbe byorolysls ot ATP to ADP + Pl.

A common actlve transport pump ls tbe soolum/potasslum
ATPase (Na/K pump), touno ln all anlmal cell membranes.
Tbls pump contlnually uses ATP to actlvely pump soolum
lons out ot tbe cell ano potasslum lons lnto tbe cell. Tbls
creates lon graolents across tbe cell membrane, wblcb can
be useo to regulate water potentlal ano orlve otber process
(sucb as absorptlon ln tbe gut, see p65).

Na/K
pump
Na
+
ATP
ADP + Pl
K
+

Effect of concentration difference on rate of transport
Tbe tbree klnos ot transport can be olstlngulsbeo eperlmentally by tbe ettect ot solute concentratlon on
lts rate ot transport:
Llplo olttuslon sbows a llnear relatlonsblp. Tbe greater tben
concentratlon oltterence tbe great tbe rate ot olttuslon (see
Flsk's law p44).
Facllltateo olttuslon bas a curveo relatlonsblp wltb a
malmum rate. At blgb concentratlons tbe rate ls llmlteo by
tbe number ot transport protelns.
Actlve transport bas a blgb rate even wben tbere ls no
concentratlon oltterence across tbe membrane. Actlve
transport stops lt cellular resplratlon stops, slnce tbere ls no energy.

5unnary of Menbrane Transport
nethod uses energy!
which part of
nenbrane!
specific!
concentration
gradient
Llplo Dlttuslon
" "" "
pbospbollplo bllayer
" "" " $
Osmosls
" "" "
pbospbollplo bllayer
! !! ! $
Facllltateo Dlttuslon
" "" "
protelns
! !! ! $
Actlve Transport
! !! !
protelns
! !! ! %

concentratlon oltterence
r
a
t
e

o
t

t
r
a
n
s
p
o
r
t
actlve transport
llplo
olttuslon
tacllltateo
olttuslon

BLANK PAGE


PhysioIogy
Exchange
All organlsms neeo to ecbange substances sucb as tooo, waste, gases ano beat wltb tbelr surrounolngs.
Tbese substances must olttuse between tbe organlsm ano tbe surrounolngs. Tbe rate at wblcb a substance
can olttuse ls glven by Flck's law:
olstance
oltterence lon concentrat area surtace
Dlttuslon ot Rate

From Flck's law we can preolct tbat, ln oroer to support a tast rate ot olttuslon, ecbange surtaces must
bave:
a large surtace area
a small olstance between tbe source ano tbe oestlnatlon
a mecbanlsm to malntaln a blgb concentratlon graolent across tbe gas ecbange surtace.

Tbls table summarlses bow tbese requlrements are met ln tbe buman olgestlve ano gas ecbange systems.
systen Iarge surface area snaII distance high concentration
gradient
Human small
lntestlne
7m long, tolos, vllll ano mlcrovllll
glve surtace area ot 2000m
blooo caplllarles close to
surtace ot vlllus
stlrreo by perlstalsls ano
by mlcrovllll
Human
clrculatory
system
100m ot caplllarles wltb a surtace
area ot 6000m
caplllary walls are only
one tlatteneo cell tblck
constant blooo tlow
replenlsbes tbe blooo
Human lungs
600 mllllon alveoll wltb a total
area ot 100m
alveoll walls are only one
tlatteneo cell tblck
constant ventllatlon
replaces tbe alr
For comparlson, a tennls court bas an area ot about 260 m ano a tootball pltcb bas an area ot about 5000 m.


EpitheIiaI Tissue
Lpltbellal tlssue ls tbe name glven to tbe layer ot cells coverlng all tbe eternal ano lnternal surtaces ot tbe
booy. Lcbange tberetore takes place tbrougb epltbellal tlssue ano tbe cells are aoapteo tor ecbange.
Tbere are many oltterent klnos ot epltbellal tlssue:
Squamous epltbellum ls touno surrounolng tbe alveoll (see p46). Tbe cells are etremely tlatteneo, llke
pancakes, ano are otten so tbln tbat tbe nucleus makes a bulge.
Lnootbellum ls touno llnlng caplllarles ano otber blooo vessels (see unlt 2). Tbese are also tlat squamous
cells, but on an lnternal surtace (enoo=lnsloe).
Columnar epltbellum ls touno llnlng tbe allmentary canal (see p62). Tbe cells are tblck, but are llneo wltb
mlcrovllll to glve a large surtace area.
Clllateo epltbellum ls touno on tbe tracbea ano broncbl (see p46). Tbese cells are not aoapteo tor
ecbange, but tor lubrlcatlon ano protectlon.
Lploermls ls touno on tbe outer surtace ot tbe skln. |t torms a tougb, lmpermeable barrler preventlng
oeslccatlon (water loss) ano lntectlon.


The Gas Exchange 5ysten
Tbls olagram sbows tbe gas ecbange system ln bumans:
laryn
tracbea
broncbus
lung
beart
sternum
cartllage
lntercostal
muscles
broncblole
rlb
pleural
membrane
alveolus
olapbragm

Tbe gas ecbange system ls also reterreo to as tbe resplratory system, but tbls can be contuslng as
resplratlon takes place ln all cells, ano ls qulte olstlnct trom gas ecbange. Tbe actual gas ecbange surtace ls
on tbe alveoll lnsloe tbe lungs.
broncblole
clllateo epltbellal cells
mucus-secretlng
epltbellal cells
alveolus
aIveoIi
squamous epltbellum
ot alveolus
blooo caplllary
enootbellum
ot caplllary
reo blooo cells
banos ot smootb
muscle arouno
broncblole

Tbls surtace meets tbe tbree requlrements ot Flck's law:
A large surtace area. Altbougb eacb alveolus ls tlny, an average aoult bas about 600 mllllon alveoll, glvlng
a total surtace area ot about 100m, so tbe area ls buge.

A small olstance between tbe source ano tbe oestlnatlon. Tbe walls ot tbe alveoll are composeo ot a
slngle layer ot tlatteneo epltbellal cells, as are tbe walls ot tbe caplllarles, so gases neeo to olttuse tbrougb
just two tbln cells.
A mecbanlsm to malntaln a blgb concentratlon graolent across tbe gas ecbange surtace. Tbe steep
concentratlon graolent across tbe gas ecbange surtace ls malntalneo ln two ways: by blooo tlow on one
sloe ano ventllatlon on tbe otber sloe. Tbls means oygen can always olttuse oown lts concentratlon
graolent trom tbe alr to tbe blooo, wblle at tbe same tlme carbon ololoe can olttuse oown lts
concentratlon graolent trom tbe blooo to tbe alr

Alveolar alr space
8looo caplllary
Alveolar squamous epltbellum
caplllary enootbellum
reo blooo cell
TEM of Hunan Lungs

Tbe large surtace area ano sbort olstance tbat are loeal tor gas ecbange also cause a problem: water loss.
Water lnevltably olttuses oown lts concentratlon graolent trom tbe tlssue tlulo ano alveoll cells lnto tbe alr
ln tbe alveoll, so tbe alr ln tbe alveoll ls constantly molst. Tbls ls wby ebaleo alr contalns more water tban
normal, lnbaleo alr, ano tbls represents a slgnltlcant loss ot water trom tbe booy. However, by bavlng tbe
gas ecbange surtace oeep lnsloe tbe booy at tbe eno ot long narrow broncbloles, tbe water loss ls
mlnlmlseo. Tbe molst alveolar alr means tbat tbere ls less ot a olttuslon graolent (ano so less water ls lost)
tban lt tbe alveoll were eposeo to outsloe ory alr. Tbe epltbellal cells secrete a soapy surtactant to reouce
tbe surtace tenslon ot tbe water (oue to byorogen bonos) ano make lt less "stlcky". Wltbout tbls surtactant
tbe alveoll woulo collapse, ano tbls can be a problem ln premature bables.

Some ot tbe epltbellal cells ot tbe broncbloles secrete mucus, wblcb traps bacterla ano otber mlcroscoplc
partlcles tbat enter tbe lungs. Tbls mucus ls constantly swept upwaros by tbe cllla ot tbe clllateo epltbellal
cells to tbe tbroat, wbere lt ls swalloweo ano any bacterla ln lt are kllleo by tbe aclo ln tbe stomacb.
Pbagocyte cells mlgrate trom tbe blooo caplllarles to tbe alveolar alr space to klll any bacterla tbat bave not
been trappeo by tbe mucus.


VentiIation
ventllatlon means tbe movement ot alr over tbe gas ecbange surtace (also known as breatblng). Lungs are
not muscular ano cannot ventllate tbemselves, but lnsteao tbe wbole tbora moves ano cbanges slze, oue to
tbe actlon ot two sets ot muscles: tbe lntercostal muscles ano tbe olapbragm. Tbese movements are
transmltteo to tbe lungs vla tbe pleural sac surrounolng eacb lung. Tbe outer membrane ls attacbeo to tbe
tbora ano tbe lnner membrane ls attacbeo to tbe lungs. 8etween tbe membranes ls tbe pleural tlulo, wblcb
ls lncompresslble, so lt tbe tbora moves, tbe lungs move too. Tbe alveoll are elastlc ano collapse lt not
belo stretcbeo by tbe tbora.

Tbe muscle contractlons cbange tbe volume ot tbe tbora, wblcb ln turn cbanges tbe pressure ln tbe lungs
(by 8oyle's law), wblcb ln turn causes alr to move. ventllatlon ln bumans ls tloal, wblcb means tbe alr tlows
ln ano out by tbe same route. Tbe rule ls tbat 8'/ 8">8#& ="%>& =/%3 8 7'!7 0/-&&4/- .% 8 "%> 0/-&&4/-. Tbese
volume ano pressure cbanges are sbown ln tbls grapb:
0 1 2 3 4
8.3%&07-/'$ 0/-&&4/-
below
atmospberlc
pressure
above
atmospberlc
pressure
Tlme (s)
D+&0'/8.'%+ EF0'/8.'%+ 6-&.
P
r
e
s
s
u
r
e
l
n

a
l
v
e
o
l
l
v
o
l
u
m
e
o
t

l
u
n
g
s
tloal
volume

|nsplratlon

Tbe olapbragm contracts ano tlattens oownwaros ano tbe eternal lntercostal
muscles contract, pulllng tbe rlbs up ano out.
Tbls lncreases tbe volume ot tbe tbora ano tbe lungs, ano stretcbes tbe elastlc-
walleo alveoll.
Tbls oecreases tbe pressure ot alr ln tbe alveoll below atmospberlc.
Alr tlows ln trom blgb pressure to low pressure.
Normal
eplratlon

Tbe olapbragm relaes ano curves upwaros ano tbe eternal lntercostal muscles
rela, allowlng tbe rlbs to tall.
Tbls oecreases tbe volume ot tbe tbora ano tbe lungs, ano allows tbe alveoll ano
broncbloles to sbrlnk by elastlc recoll.
Tbls lncreases tbe pressure ot alr ln tbe alveoll above atmospberlc.
Alr tlows out trom blgb pressure to low pressure.
Forceo
eplratlon
Tbe aboomlnal muscles contract, pusblng tbe olapbragm upwaros
Tbe lnternal lntercostal muscles contract, pulllng tbe rlbs oownwaro
Tbls glves a larger ano taster eplratlon, useo ln eerclse

PuInonary VentiIation
Pulmonary ventllatlon ls tbe volume alr ventllatlng tbe lungs eacb mlnute. |t ls calculateo as tbe proouct ot
tbe ventllatlon rate ano tbe tloal volume.
pulmonary ventllatlon = ventllatlon rate tloal volume
Tbe ventllatlon rate can be calculateo trom tbe pressure grapb by measurlng tbe tlme taken tor one
ventllatlon cycle ano uslng tbe tormula:
(s) tlme cycle
60
mlnute) per (breatbs rate n ventllatlo =
Tbe tloal volume ls tbe normal volume ot alr breatbeo ln eacb breatb (also calleo tbe breatblng oeptb). |t
can be measureo trom tbe volume grapb.

8otb tbe ventllatlon rate ano tbe tloal volume can be varleo by tbe booy. Wben tbe booy eerclses tbe
pulmonary ventllatlon can lncrease so tbat
oygen can olttuse trom tbe alr to tbe blooo taster
carbon ololoe can olttuse trom tbe blooo to tbe alr taster
Tbese cbanges allow aeroblc resplratlon ln muscle cells to contlnue tor longer.

ventiIation rate
{breaths nin
-1
}
tidaI voIune
{cn
3
breath
-1
}
puInonary ventiIation
{cn
3
nin
-1
}
at rest 12 500 6 000
at exercise 18 1000 18 000

Gas Exchange and VentiIation
|t lmportant to be clear about tbe meanlng ot tbe terms gas ecbange ano ventllatlon. Gas ecbange ls
wben certaln gases (usually oygen ano carbon ololoe) are moveo between tbe envlronment ano tbe
blooo. ventllatlon ls a muscular movement tbat belps to speeo up gas ecbange. ventllatlon lncreases tbe
rate ot gas ecbange by lncreaslng tbe concentratlon oltterence across tbe resplratory surtace, wblcb
lncreases tbe rate ot olttuslon by Flck's law (p44). Tbls table summarlses tbe oltterences:
Gas Exchange VentiIation
uses olttuslon uses mass tlow
passlve (no energy neeoeo) actlve (tbora muscles use ATP energy)
gases move oown tbelr own concentratlon graolents
(so can be ln oltterent olrectlons)
all gases ln alr move togetber ln one olrectlon
slow qulck


Lung Diseases
Tbe teatures ot tbe lungs tbat make tbem so gooo at gas ecbange also makes tbem susceptlble to olsease.
Tbe large volumes ot alr passlng tbrougb tbe lungs may carry lntectlous patbogens or otber mlcroscoplc
partlcles tbat cause olsease. We sball look at tlve olseases ot tbe lungs: astbma, tuberculosls, empbysema,
lung cancer ano tlbrosls.

1. Asthna
Astbma ls an allerglc response tbat causes olttlculty breatblng, wbeezlng, tlgbt cbest ano cougblng. |t ls
tbougbt to attect 10 ot tbe worlo's populatlon ano ls responslble tor 2000 oeatbs per year ln tbe UK.

Course of Disease
1. Astbma ls causeo by pbyslcal tactors calleo allergens ln tbe envlronment. Tbese allergens lncluoe pollen,
oust mltes taeces ano tur.
2. Tbese allergens trlgger an lntlammatory response by
tbe lmmune system (see p73). Wblte blooo cells calleo
mast cells release blstamlnes (see unlt 5), wblcb cause
tbe smootb clrcular muscles ot tbe broncbloles to
contract, narrowlng tbe alrways broncboconstrlctlon.
3. Tbe epltbellal cells also secrete more mucus, wblcb
turtber blocks tbe alrways.
4. Tbe constrlcteo broncbloles stlmulate wbeezlng ano
cougblng as tbe lungs try to loosen tbe mucus.
5. Tbe constrlctlons reouce tbe tloal volume, so alveolar
alr ls only replaceo slowly. Tbe oygen concentratlon
graolent across tbe alveolar epltbellum ls reouceo, so
tbe rate ot olttuslon ln tbe alveoll ls reouceo by Flck's
law. Less oygen olttuses lnto tbe blooo, so less oygen ls avallable tor cellular resplratlon tbrougbout
tbe booy.

Risk Factors
Tbe rlsk tactor tor astbma ls eposure to allergens. As well as pollen, taeces ot oust mltes ano anlmal tur,
otber tactors tbat can contrlbute to astbma lncluoe pollutlng gases llke sulpbur ololoe, eerclse, colo
weatber, lntectlon ano stress. Astbma can be treateo by lnballng orugs tbat rela tbe smootb muscles ano
by antl-lntlammatory orugs.

constrlcteo
broncbloles
sectlon
bere

2. PuInonary TubercuIosis
Pulmonary Tuberculosls (or T8) ls an lntectlous olsease causeo by tbe bacterlum G#$%*8$.-/'43 .4*-/$4"%&'&.
|n 19
tb
-century Lnglano one ln tlve oleo ot T8, ano altbougb tbe olsease bas been almost eraolcateo ln tbe
oevelopeo worlo, lt ls stlll a major klller ln tbe oeveloplng natlons, responslble tor 1.5 mllllon oeatbs ln
2006. Tbe symptoms are a perslstent cougb wltb cbest palns, tlreoness, a loss ot appetlte ano welgbt loss,
ano ln serlous cases cougblng up blooo, wastlng away ano oeatb.

Course of Disease
1. T8 ls transmltteo by aerosol oroplets trom cougbs ano sneezes ot lntecteo persons. |ntectlon ls most
llkely to result trom prolongeo eposure.
2. Tbe bacterlal cells are breatbeo ln ano lnvaoe tbe epltbellal
cells ot tbe alveoll ano broncbloles. Here tbey multlply to
torm lumps calleo tubercles, ln wblcb tbe bacterla remaln
allve but oormant.
3. Tbe tubercles stlmulate an lntlammatory response by tbe
wblte blooo cells ot tbe lmmune system, resultlng ln tbe
tormatlon ot tlbrous scar tlssue. Tbls scar tlssue reouces tbe
elastlclty ot tbe alveoll ano tblckens tbelr walls, so reouclng
tbe rate ot oygen olttuslon.
4. Atter a oelay ot montbs to years tbe bacterla emerge trom
tbe tubercles ano start reproouclng lnsloe tbe lung epltbellal
cells, kllllng tbem. Tbe oamageo alveoll bave a smaller
surtace area, so turtber reouclng tbe rate ot gas ecbange.
5. Tbe T8 bacterla can also spreao tbrougb tbe blooostream
to otber organs, llke tbe kloney, bone ano nervous tlssue,
wblcb are oestroyeo as well. Tbls causes weakness as tbe
booy wastes away ano tbe bacterla appear to consume
tbe booy bence tbe olo name tor T8: consumptlon.
tubercle
chest x-ray
oamageo
alveoll
scar
tlssue
Iung tissue

Risk Factors
Tbe maln rlsk tactor tor T8 ls overcrowolng, sucb as ln crowoeo slums or bospltals, as tbls allows T8 to
spreao raploly between bosts. Otber tactors lncluoe poor olet ano A|DS, as tbese botb lmpalr tbe lmmune
system. Slnce lt ls a bacterlal olsease, T8 can be treateo by antlblotlcs, ano can also be preventeo by tbe
8CG vacclne. Untortunately, tbe lncloence ot T8 ls currently rlslng oue to reslstance ot tbe bacterlum to
tbe 8CG vacclne ano to tbe lncrease ln A|DS.


3. Enphysena
Lmpbysema ls a lung olsease cbaracterlseo by severe breatblng olttlcultles resultlng ln an lnablllty to oo any
eerclse. |t causeo almost ecluslvely by smoklng ano 20 ot all smokers sutter trom empbysema, 10 ot
absence trom work ln tbe UK ls oue to empbysema ano lt kllls 20 000 per year ln tbe UK.

Course of Disease
1. Tbe tar ln clgarette smoke stlmulates tbe wblte blooo cells to release lntlammatory protease enzymes ln
tbe lungs.
2. Tbese protease enzymes olgest tbe proteln elastln, wblcb torms tbe elastlc tlssue ln tbe epltbellal cells ot
tbe alveoll. Tbe alveoll can no longer epano ano recoll, reouclng tbe tloal volume ln ventllatlon. Tbls
reouces tbe oygen olttuslon graolent, so less oygen olttuses lnto tbe blooo.
3. |n more severe cases tbe epltbellal cells are completely oestroyeo, so alveoll merge to torm large alr
sacs wltb a mucb smaller surtace area ano tblcker walls. Tbese all reouce tbe rate ot oygen olttuslon, so
less oygen ls avallable tor cellular resplratlon ano muscular actlvlty ls very olttlcult.

normal alveoll

alveoll wltb empbysema

Risk Factors
8y tar tbe most lmportant rlsk tactor tor empbysema ls smoklng, ano 20 ot all smokers sutter trom
empbysema. 10 ot absence trom work ln tbe UK ls oue to empbysema ano lt kllls 20 000 per year ln tbe
UK. Lmpbysema ls lncurable, tbougb glvlng up smoklng prevents tbe symptoms gettlng any worse. 8reatblng
pure oygen compensates tor tbe poor ettlclency ot gas ecbange, so allowlng more resplratlon.

4. Lung Cancer
Lung cancer ls tbe growtb ot ecess tlssue ln tbe lungs oue to uncontrolleo cell olvlslon ot tbe epltbellal
cells. Mutagenlc agents ln tbe envlronment cause epltbellal cells to mutate ano start to olvloe contlnuously
ano uncontrollably, tormlng a tumour. As tbe tumour grows lt can constrlct tbe broncbloles ano alveoll, so
slowlng tbe rate ot gas ecbange. Lung cancers otten spreao to otber parts ot tbe booy ano are a major
cause ot oeatb ln tbe oevelopeo worlo.

Risk Factors
Tbe rlsk tactor tor lung cancer ls eposure to tbe mutagenlc agents. Tbese agents lncluoe tobacco smoke,
asbestos ano raoon gas, wblcb ls present ln tbe alr ot some locatlons.

5. PuInonary Fibrosis
Pulmonary tlbrosls ls a severe sbortness ot breatb causeo by lnbalatlon ot tlne oust partlcles or cbemlcals.

Course of Disease
1. Tbe partlcles stlmulate an lntlammatory response ln tbe lungs, wblcb results ln tbe growtb ot tlbrous
scar tlssue arouno tbe alveoll.
2. Tbls scar tlssue tblckens tbe alveolar walls so tbat tbere ls a longer olttuslon patbway ano a smaller
surtace area tor oygen olttuslon.
3. Tbe scar tlssue also reouces tbe elastlclty ot tbe alveoll so normal passlve ebalatlon ls reouceo. Tbls
means tbere ls a smaller oygen olttuslon graolent, so less oygen reacbes tbe blooo.

Risk Factors
Tbere are bunoreos ot oltterent causes ot pulmonary tlbrosls, ano slnce tbese are usually touno ln work-
place envlronments, pulmonary tlbrosls ls known as an occupatlonal olsease. Some ot tbe maln causes are
sbown ln tbls table:
Disease Cause Risk occupation
pneumoconlosls coal oust coal mlnlng
asbestosls asbestos oemolltlon workers
slllcosls slllca oust quarrylng, mlnlng
berylllosls berylllum electronlcs, nuclear power lnoustrles
tarmer's lung moulo spores ln bay tarmlng
blro tancler's lung protelns ln blro taeces blro breeoers, poultry tarmers

Lung Diseases 5unnary
Disease Cause 5ynptons How Gas Exchange is
5Iowed
Risk Factors
astbma allergens temporary breatblng
olttlcultles, wbeezlng
broncboconstrlctlon reouces
tloal volume
pollen, oust, SO2, colo
alr.
T8 bacterlal
lntectlon
cbest paln, cougblng
blooo, tever, oeatb
lntlammatlon ano scar tlssue
make tewer, tblcker alveoll
ano reouce elastlclty.
overcrowolng, poor
olet, A|DS
empbysema smoklng permanent breatblng
olttlculty
reouceo elastlclty prevents
ebalatlon.
smoklng
lung cancer smoklng breatblng olttlculty,
welgbt loss
constrlctlons reouce tloal
volume.
smoklng, asbestos,
raoon gas.
pulmonary
tlbrosls
oust breatblng olttlculty lntlammatlon ano scar tlssue
make tewer, tblcker alveoll
ano reouce elastlclty.
coal oust, slllca oust,
moulo spores.

The Heart
lett atrlum
lett pulmonary velns
aortlc arcb
lett ventrlcle
lnterventrlcular septum
paplllary muscle
atrloventrlcular (blcusplo) valve
valve tenoons
arterles to beao
superlor vena cava
carolac muscle
aorta
rlgbt atrlum
semllunar (pulmonary) valve
atrloventrlcular (trlcusplo) valve
rlgbt ventrlcle
lnterlor vena cava
pulmonary artery

Tbe buman beart bas tour cbambers: two tbln-walleo atrla on top, wblcb recelve blooo, ano two tblck-
walleo ventrlcles unoerneatb, wblcb pump blooo. velns carry blooo lnto tbe atrla ano arterles carry blooo
away trom tbe ventrlcles. 8etween tbe atrla ano tbe ventrlcles are atrloventrlcular valves, wblcb prevent
back-tlow ot blooo trom tbe ventrlcles to tbe atrla. Tbe lett valve bas two tlaps ano ls calleo tbe blcusplo (or
mltral) valve, wblle tbe rlgbt valve bas 3 tlaps ano ls calleo tbe trlcusplo valve. Tbe valves are belo ln place by
valve tenoons (beart strlngs) attacbeo to paplllary muscles, wblcb contract at tbe same tlme as tbe
ventrlcles, bololng tbe valves closeo. Tbere are also two seml-lunar valves ln tbe arterles (tbe only
eamples ot valves ln arterles) calleo tbe pulmonary ano aortlc valves.

Tbe lett ano rlgbt balves ot tbe beart are separateo by tbe lnter-ventrlcular septum. Tbe walls ot tbe rlgbt
ventrlcle are 3 tlmes tblnner tban on tbe lett ano lt proouces less torce ano pressure ln tbe blooo. Tbls ls
partly because tbe blooo bas less tar to go (tbe lungs are rlgbt net to tbe beart), but also because a lower
pressure ln tbe pulmonary clrculatlon means tbat less tlulo passes trom tbe caplllarles to tbe alveoll. Tbe
lnternal volume ot tbe lett ano rlgbt ventrlcles ls tbe same.

Tbe beart ls maoe ot carolac muscle, composeo ot cells calleo myocytes. Wben myocytes recelve an
electrlcal lmpulse tbey contract togetber, causlng a beartbeat. Slnce myocytes are constantly actlve, tbey
bave a great requlrement tor oygen, so are teo by numerous caplllarles trom two coronary arterles. Tbese
arlse trom tbe aorta as lt leaves tbe beart. 8looo returns vla tbe coronary slnus, wblcb oralns olrectly lnto
tbe rlgbt atrlum.


slno-atrlal nooe (SAN)
atrlo-ventrlcular nooe (AvN)
8unole ot Hls
Purklnje tlbres
The Cardiac CycIe
Carolac muscle contracts about 75 tlmes per mlnute, pumplng arouno 75 cm ot blooo trom eacb ventrlcle
eacb beat (tbe stroke volume). |t ooes tbls contlnuously tor up to 100 years.

Carolac muscle ls myogenlc, wblcb means tbat lt
can contract on lts own, wltbout neeolng nerve
lmpulses. Contractlons are lnltlateo wltbln tbe
beart by tbe slno-atrlal nooe (SAN, or
pacemaker) ln tbe rlgbt atrlum. Tbls
etraorolnary tlssue acts as a clock, ano contracts
spontaneously ano rbytbmlcally about once a
secono, even wben surglcally removeo trom tbe
beart.

Tbere ls a compllcateo sequence ot events at eacb beartbeat calleo tbe carolac cycle. Tbe carolac cycle bas
tbree stages:

1. AtriaI 5ystoIe. Tbe SAN contracts ano transmlts electrlcal lmpulses tbrougbout tbe atrla, wblcb botb
contract, pumplng blooo lnto tbe ventrlcles. Tbe ventrlcles are electrlcally lnsulateo trom tbe atrla, so
tbey oo not contract at tbls tlme. Tbe blooo can't tlow back lnto tbe velns because ot tbe valves ln tbe
velns.

2. VentricuIar 5ystoIe. Tbe electrlcal lmpulse passes trom tbe atrloventrlcular nooe (AvN) to tbe
Purklnje (or Purkyne) tlbres, wltb a sbort but lmportant oelay ot about 0.1s. Tbe Purklnje tlbres pass
oown tbrougb tbe lnterventrlcular septum as tbe bunole ot Hls, wblcb ls lnsulateo trom tbe surrounolng
muscle cells, so tbe ventrlcles oo not contract yet. At tbe base ot tbe ventrlcles tbe Purklnje tlbres
spreao out ano lnltlate ventrlcular contractlon. Tbe ventrlcles tberetore contract sbortly atter tbe atrla,
trom tbe bottom up, squeezlng blooo upwaros lnto tbe arterles. Tbe blooo can't go lnto tbe atrla
because ot tbe atrloventrlcular valves, wblcb are torceo sbut wltb a "lub" souno.

3. DiastoIe. Tbe atrla ano tbe ventrlcles rela, wblle tbe atrla tlll wltb blooo. Tbe semllunar valves ln tbe
arterles close as tbe arterlal blooo pusbes agalnst tbem, maklng a "oup" souno.


Tbe events ot tbe tbree stages are sbown ln tbe cbart below. Tbe pressure cbanges sbow most clearly wbat
ls bappenlng ln eacb cbamber. 8looo tlows because ot pressure oltterences, ano lt aIways fIows fron a
high pressure to a Iow pressure, lt lt can. So ourlng atrlal systole tbe atrla contract, maklng tbe atrlum
pressure blgber tban tbe ventrlcle pressure, so blooo tlows trom tbe atrlum to tbe ventrlcle. Tbe artery
pressure ls blgber stlll, but blooo can't tlow trom tbe artery back lnto tbe beart oue to tbe seml-lunar
valves. Tbe valves are largely passlve: tbey are openeo by blooo tlowlng tbrougb tbem tbe rlgbt way ano are
torceo closeo wben blooo trles to tlow tbrougb tbem tbe wrong way. Wbenever llnes cross ln tbe pressure
grapb lt means tbat a valve opens or closes.

0.1 0 0.2 0.3 0.4 0.5 0.6 0.7 0.8
0.1 0 0.2 0.3 0.4 0.5 0.6 0.7 0.8
AtriaI 5ystoIe
atrla contract
blooo enters ventrlcles
VentricuIar 5ystoIe
ventrlcles contract
blooo enters arterles
DiastoIe
atrla ano ventrlcals botb rela
blooo enters atrla ano ventrlcles
P
r
e
s
s
u
r
e

{
k
P
a
}
ECG
PCG
Nane
E
v
e
n
t
s
Tlme (s)
0
5
10
15
20
ln ventrlcle
ln atrlum
ln artery
ln artery
ln atrlum
ln ventrlcle
atrioventricuIar
vaIves cIose
atrioventricuIar
vaIves open
seniIunar
vaIves cIose
seniIunar
vaIves open
"lub" "oup"

Tbls olagram just sbows one sloe ot tbe beart. Tbe two sloes bave loentlcal traces ecept tbat tbe
pressures ln tbe rlgbt sloe are lower tban tbose ln tbe lett sloe.

Tbe PCG (or pbonocarologram) ls a recorolng ot tbe sounos tbe beart makes. Tbe carolac muscle ltselt
ls sllent ano tbe sounos are maoe by tbe valves closlng. Tbe tlrst souno (lub) ls oue to tbe
atrloventrlcular valves closlng ano tbe secono (oup) ls oue to tbe seml-lunar valves closlng.
Tbe LCG (or electrocarologram) ls a recorolng ot tbe electrlcal actlvlty ot tbe beart. Tbere are
cbaracterlstlc waves ot electrlcal actlvlty marklng eacb pbase ot tbe carolac cycle. Cbanges ln tbese LCG
waves can be useo to belp olagnose problems wltb tbe beart.

Cardiac Output
Carolac Output ls tbe amount ot blooo tlowlng tbrougb tbe beart eacb mlnute. |t ls calculateo as tbe
proouct ot tbe beart rate ano tbe stroke volume:
carolac output = beart rate stroke volume
Tbe beart rate can be calculateo trom tbe pressure grapb by measurlng tbe tlme taken tor one carolac
cycle ano uslng tbe tormula:
(s) tlme cycle
60
mlnute) per (beats rate beart =
Tbe stroke volume ls tbe volume ot blooo pumpeo ln eacb beat.

8otb tbe beart rate ano tbe stroke volume can be varleo by tbe booy. Wben tbe booy eerclses tbe carolac
output can lncrease oramatlcally so tbat
oygen ano glucose can get to tbe muscles taster
carbon ololoe ano lactate can be carrleo away trom tbe muscles taster
beat can be carrleo away trom tbe muscles taster

heart rate
{beats nin
-1
}
stroke voIune
{cn
3
beat
-1
}
cardiac output
{cn
3
nin
-1
}
at rest 75 75 5 600
at exercise 180 120 22 000

Coronary Heart Disease
Coronary beart olsease (CHD) ls causeo by a blockage ln tbe
coronary blooo system. Tbls ls tbe system tbat teeos tbe carolac
muscle cells so tbat tbey can resplre ano contract. Carolac
muscle works constantly tbrougbout llte ano ls lncapable ot
anaeroblc resplratlon, so lt bas a great oemano tor oygen ano
glucose. Tbere are two coronary arterles tbat arlse olrectly trom
tbe aorta, ano tbese spllt lnto numerous smaller arterles
(arterloles) ano tben a network ot caplllarles, wbere ecbange
wltb tbe carolac cells actually takes place. A blockage ln a
coronary artery can restrlct tbe supply ot oygen to tbe carolac
cells, kllllng tbem ano causlng a beart attack. Tbe steps are as tollows:

1. Cbolesterol ano otber lnsoluble llplos collect on tbe lnsloe ot a coronary artery. Tbls oeposlt ls calleo an
atberoma, ano lt narrows tbe lumen ot tbe
artery, restrlctlng blooo tlow atberosclerosls.
2. Tbe atberoma can collect mlnerals ano become
baroeneo to torm a rougb plaque.
3. Tbe plaque weakens tbe wall ot tbe artery, so
tbe pressure ot blooo causes a local swelllng
calleo an aneurlsm. |t tbe wall ls partlcularly weak
tbe aneurlsm may burst causlng blooo loss ano
probable oeatb.
4. Tbe plaque can also encourage tbe tormatlon ot
a blooo clot calleo a tbrombus. Alternatlvely, a
moblle clot trom elsewbere ln tbe blooo stream (an embollsm) can become loogeo ln tbe atberoma. Tbe
clot grows untll lt completely blocks tbe artery, tormlng a coronary tbrombosls.
5. Tbe tbrombosls prevents oygen reacblng tbe carolac cells oownstream ot tbe blockage, so tbey
cannot resplre ano so ole. Tbls oeatb ot myocytes ls a myocarolal lntarctlon, more commonly known as
a beart attack. Tbe severlty ot tbe beart attack oepenos on bow tar along tbe coronary artery tbe
tbrombosls ls. |t only a small part ot one ventrlcle ls kllleo tben tbe patlent wlll recover, but a
tbrombosls early ln tbe coronary artery wlll always be tatal.
coronary
arterles
lett
ventrlcle
Llplo
oeposlts
lnsloe
artery
(atberoma)
clean
artery

Tbe tlve stages ln a beart attack are summarlseo ln tbls olagram
Atherona
(tat oeposlts)
1
PIaque
(baroeneo atberoma)
2
Coronary Thronbosis
(blockage oue to blooo clot)
4
MyocardiaI lnfarction
(oeatb ot carolac cells)
5
Aneurisn
(swelllng oue to weak wall)
3

Risk Factors for Coronary Heart Disease
Tbere are a number ot rlsk tactors tbat are assoclateo wltb coronary beart olsease. Tbe more ot tbe
tactors tbat apply, tbe greater tbe rlsk ot a beart attack. Some ot tbe maln tactors are:
BIood ChoIesteroI. Cbolesterol ln tbe blooo comes trom tbe olet ano trom tbe llver, wbere lt ls
syntbeslseo. Cbolesterol ls carrleo ln large complees wltb protelns, calleo llpoprotelns. Hlgb-oenslty
llpoprotelns (HDLs) remove cbolesterol trom tlssues, so oecrease tbe rlsk ot atberomas, wblle Low-
oenslty llpoprotelns (LDLs) oellver cbolesterol to tlssues, so lncrease tbe rlsk ot atberomas.
BIood Pressure. Hlgb blooo pressure lncreases tbe rlsk ot an aneurlsm ano stlmulates tblckenlng ot
artery wall, lncreaslng tbe rlsk ot tbrombosls. Stress, olet ano lack ot eerclse can all lncrease blooo
pressure.
Genetics. 8otb blooo pressure ano tat metabollsm are attecteo by genes, so genes unooubteoly attect
tbe cbance ot a coronary tbrombosls. Tbls ooesn't mean tbat, tor some people, a beart attack ls
lnevltable, lt just means some people bave to be even more caretul about tbelr lltestyle rlsk tactors.
Diet. Hlgb levels ot saturateo tat lncrease tbe amount ot cbolesterol carrleo ln tbe blooo ano so lncrease
tbe rlsk ot atberosclerosls. Hlgb levels ot salt lncrease blooo pressure ano so lncrease tbe rlsk ot
aneurlsm. However, oletary tlbre ano vltamln C reouce tbe rlsk ot beart olsease.
5noking. Smokers are between two ano sl tlmes more llkely to sutter trom coronary beart olsease
tban non-smokers. Tbe carbon monoloe ano nlcotlne ln clgarette smoke botb cause an lncrease ln
blooo pressure.


The Digestive 5ysten
Humans, llke all anlmals, use bolozolc nutrltlon, wblcb conslsts ot tbese tlve stages:
ingestion taklng large pleces ot tooo lnto tbe booy
digestion breaklng oown tbe tooo by mecbanlcal ano cbemlcal means
absorption taklng up tbe soluble olgestlon prooucts lnto tbe booy's cells
assiniIation uslng tbe absorbeo materlals
egestion ellmlnatlng tbe unolgesteo materlal. (Do not contuse egestlon, wblcb ls tbe ellmlnatlon ot
materlal trom a booy cavlty, wltb ecretlon, wblcb ls tbe ellmlnatlon ot waste materlal proouceo trom
wltbln tbe booy's cells.)

The AIinentary CanaI
Tbe buman olgestlve system comprlses a long tube, tbe allmentary canal or olgestlve tract (or slmply gut)
wblcb etenos trom tbe moutb to tbe anus, togetber wltb a number ot assoclateo glanos: tbe sallvary
glanos, tbe pancreas ano tbe llver.

tongue
sallvary
glanos
oesopbagus
llver
ouooenum
lleum
eplglottls
stomacb
pancreas
colon
rectum
anus


Tbe olgestlve system ls maoe up ot oltterent tlssues oolng oltterent jobs. Tbe llnlng wall ot tbe allmentary
canal appears oltterent ln oltterent parts ot tbe gut, retlectlng tbelr oltterent roles, but always bas tbese tour
baslc layers:
Mucosa
5ubnucosa
MuscIe
5erosa
Lunen
(space)
clrcular
longltuolnal
caplllarles
lacteal
epltbellum
glano ln mucosa
blooo vessels
lympb vessel
glano ln submucosa
ouct to eternal
glano (e.g. llver)
vlllus
mlcrovllll
(brusb boroer)

Tbe mucosa, wblcb secretes olgestlve julces ano absorbs olgesteo tooo. |t ls otten toloeo to lncrease lts
surtace area. Tbere ls a layer ot columnar epltbellal cells llnlng tbe mucosa. Tbese epltbellal cells contaln
mlcrovllll, membrane protelns tor tacllltateo olttuslon ano actlve transport, mltocbonorla, ano
membrane-bouno enzymes. Lpltbellal cells are constantly worn away by trlctlon wltb tooo movlng
tbrougb tbe gut, so are constantly belng replaceo.
Tbe submucosa, wblcb contalns blooo vessels, lympb vessels ano nerves to control tbe muscles. |t may
also contaln secretory glanos.
Tbe muscle layer, wblcb ls maoe ot smootb muscle, unoer lnvoluntary control. |t can be subolvloeo lnto
clrcular muscle (wblcb squeezes tbe gut wben lt contracts) ano longltuolnal muscle (wblcb sbortens tbe
gut wben lt contracts). Tbese two muscles tberetore bave opposlte ettects ano so are antagonlstlc. Tbe
comblnatlon ot tbese two muscles allows tooo to be pusbeo along tbe gut by perlstalsls.
Tbe serosa, wblcb ls a tbln, tougb layer ot connectlve tlssue tbat bolos tbe gut togetber, ano attacbes lt
to tbe aboomen.


Parts of the AIinentary CanaI
1. Mouth {BuccaI cavity}. Tbe teetb ano tongue pbyslcally break up tbe tooo lnto small pleces wltb a
larger surtace area, ano torm lt lnto a ball or bolus. Tbe sallvary glanos secrete sallva, wblcb contalns
water to olssolve soluble substances, mucus tor lubrlcatlon, lysozymes to klll bacterla ano sallvary
amylase to olgest starcb. Tbe tooo bolus ls swalloweo by an lnvoluntary retle actlon tbrougb tbe
pbaryn (tbe back ot tbe moutb). Durlng swallowlng tbe tracbea ls blockeo ott by tbe eplglottls to stop
tooo enterlng tbe lungs.

2. Oesophagus {guIIet}. Tbls ls a slmple tube tbrougb tbe tbora, wblcb connects tbe moutb to tbe rest
ot tbe gut. No olgestlon takes place bere. Tbere ls a epltbellum, no vllll, a tew glanos secretlng mucus,
ano a tblck layer ot clrcular ano longltuolnal muscle to propel tbe tooo by perlstalsls. Perlstalsls ls a wave
ot clrcular muscle contractlon, wblcb passes oown tbe gut ano ls completely lnvoluntary. Tbe
oesopbagus ls a sott tube tbat can be closeo, unllke tbe tracbea, wblcb ls a baro tube, belo open by rlngs
ot cartllage.
clrcular muscle
contracteo
+
longltuolnal muscle
relaeo
clrcular muscle
contracteo
+
longltuolnal muscle
relaeo
clrcular muscle
relaeo
+
longltuolnal muscle
contracteo
clrcular muscle
relaeo
+
longltuolnal muscle
contracteo
Fooo

3. 5tonach. Tbls ls an epanoable bag wbere tbe tooo ls storeo tor up to a tew bours. Tbere are tbree
layers ot muscle to cburn tbe tooo lnto a llqulo calleo cbyme. Tbls cblme ls graoually releaseo ln to tbe
small lntestlne by a spblncter, a reglon ot tblck clrcular muscle tbat acts as a valve. Tbe mucosa ot tbe
stomacb wall bas no vllll, but ooes bave numerous gastrlc plts (10
4
cm
-2
) leaolng to gastrlc glanos ln tbe
mucosa layer. Tbese glanos secrete gastrlc julce, wblcb contalns: byorocblorlc aclo (pH 1) to klll bacterla
(tbe aclo ooes not belp olgestlon, ln tact lt blnoers lt by oenaturlng most enzymes), mucus to lubrlcate
tbe tooo ano to llne tbe epltbellum to protect lt trom tbe aclo, ano some protease enzymes. No otber
olgestlon takes place ln tbe stomacb.

4. 5naII lntestine. Tbe tlrst 30cm ot tbe small lntestlne ls calleo tbe ouooenum. Altbougb tbls ls sbort,
almost all tbe olgestlon takes place bere, oue to two secretlons: pancreatlc julce ano blle. Pancreatlc
julce ls secreteo by tbe pancreas lnto tbe ouooenum tbrougb tbe pancreatlc ouct. Pancreatlc julce
contalns numerous amylase, protease ano llpase enzymes. 8lle ls secreteo by tbe llver, storeo ln tbe gall
blaooer, ano releaseo lnto tbe ouooenum tbrougb tbe blle ouct. 8lle ooesn't contaln any enzymes, but lt
ooes contaln blle salts to alo llplo olgestlon, ano tbe alkall soolum byorogen carbonate to neutrallse tbe

stomacb aclo. Tbls alkall glves cbyme ln tbe ouooenum a pH ot arouno 7.5, so tbe pancreatlc enzymes
can work at tbelr optlmum pH. Tbe mucosa ot tbe ouooenum bas tew vllll, slnce tbere ls no absorptlon,
but tbe submucosa contalns glanos secretlng mucus ano soolum byorogen carbonate.

Tbe rest ot tbe small lntestlne ls calleo tbe |leum. Tbls ls tbe slte ot tlnal olgestlon ano absorptlon. Tbere
are numerous glanos ln tbe mucosa ano submucosa secretlng enzymes, mucus ano soolum byorogen
carbonate. To malmlse tbe rate ot absorptlon tbe lleum bas tbe tbree teatures olctateo by Flck's law:
Tbe lleum bas a buge surtace area. |t ls over 6m long, tbe mucosa bas large clrcular tolos, vllll ano
tbe epltbellal cells bave mlcrovllll. Don't contuse tbese two: vllll are large structures composeo ot
bunoreos ot cells tbat can easlly be seen wltb a llgbt mlcroscope, wblle mlcrovllll are small sub-
cellular structures tormeo by tbe tololng ot tbe plasma membrane ot lnolvloual epltbellal cells.
Mlcrovllll can only be seen clearly wltb an electron mlcroscope, ano appear as a tuzzy brusb
boroer unoer tbe llgbt mlcroscope. Tbe total lnternal surtace area ot tbe lleum ls over 2000m.
circuIar foIds in nucosa viIIi nicroviIIi
40 mm
epltbellal cell
500 m
1 m

Tbere ls a sbort olttuslon olstance. Tbere ls a network ot blooo caplllarles ln tbe submucosa ot
eacb vlllus, so between tbe lumen ot tbe gut ano tbe blooo tbere ls just one layer ot epltbellum
llnlng tbe mucosa ano one layer ot enootbellum llnlng tbe caplllarles.
A blgb concentratlon graolent ls malntalneo by mllng tbe tlulos on eltber sloe ot tbe ecbange
surtace. On tbe lumen sloe, tbe clrcular ano longltuolnal muscles propel tbe cbyme by perlstalsls,
ano ml tbe contents by penoular movements (bl-olrectlonal perlstalsls). Tbe mlcrovllll can also
wave to stlr tbe contents near tbe epltbellal cells. On tbe blooo sloe, tbe blooo tlow ensures
tbere ls always a low concentratlon ot nutrlents.

5. Large lntestine. Tbe large lntestlne comprlses tbe caecum, appenol, colon ano rectum. Fooo can
speno 36 bours ln tbe large lntestlne, wblle water ls absorbeo to torm seml-sollo taeces. Tbe mucosa
contalns vllll but no mlcrovllll, ano tbere are numerous glanos secretlng mucus. Faeces ls maoe up ot
plant tlbre (cellulose malnly), cbolesterol, blle, mucus, mucosa cells (250 g ot cells are lost eacb oay),
bacterla ano water, ano ls releaseo by tbe anal spblncter. Tbls ls a rare eample ot an lnvoluntary muscle
tbat we can learn to control (ourlng potty tralnlng).


Digestion of carbohydrates
8y tar tbe most abunoant carbobyorate ln tbe buman olet ls starcb (ln breao, potatoes, cereal, rlce, pasta,
blscults, cake, etc). Starcb ls olgesteo to glucose ln two stages:
glucose
maltase
maltose
amylase
starcb
1. 5aIivary anyIase starts tbe olgestlon ot starcb ln tbe moutb. very llttle olgestlon actually takes place,
slnce amylase ls qulckly oenatureo ln tbe stomacb, but ls ooes belp to clean tbe moutb ot starcb ano
reouce bacterlal lntectlon.
2. Pancreatic anyIase olgests all tbe remalnlng starcb ln tbe ouooenum. Amylase olgests starcb
molecules trom tbe enos ot tbe cbalns ln two-glucose unlts, tormlng tbe olsaccbarloe maltose. Glycogen
ls also olgesteo bere.
3. Disaccharidases ln tbe membrane ot tbe lleum epltbellal cells complete tbe olgestlon ot olsaccbarloes
to monosaccbarloes. Tbls lncluoes maltose trom starcb olgestlon as well as any sucrose ano lactose ln
tbe olet. Tbere are tbree lmportant olsaccbarloase enzymes:
glucose
maltase
maltose
tructose glucose
sucrase
sucrose +
galactose glucose
lactase
lactose +
Tbe olsaccbarloase enzymes are unusual ln tbat tbey are locateo ln tbe membrane ot tbe lleum epltbellal
cells (see step D ln tbe olagram below). Tbls means tbe glucose ls proouceo at tbe cells wbere lt
neeos to be absorbeo lnto tbe booy.


Absorption of GIucose
Glucose ano tbe otber monosaccbarloes are absorbeo trom tbe gut by a speclal klno ot actlve transport
calleo coupleo actlve transport. |n coupleo actlve transport tbe monosaccbarloes are transporteo by a
tacllltateo olttuslon proteln, wblcb ls coupleo to an actlve transport proteln.
1
2
4
3
D
Na
+
Na
+
K
+
K
+
blooo
caplllary
eplltbellum
lumen
ot gut
tlssue
tlulo
G
G
G
enootbellum
5
mlcrovllll
ATP ADP
+ P
i

1. Tbe actlve transport proteln ls tbe soolum-potasslum ATPase (see p41), wblcb ls present ln all anlmal
cell membranes. Tbls proteln contlnuously pumps soolum lons out ot tbe epltbellal cell ano potasslum
lons lnto tbe cell, uslng tbe energy trom tbe byorolysls ot ATP to oo so. 8ecause tbls ls actlve transport,
tbe lons are pumpeo up tbelr concentratlon graolents, so tbere ls a large bullo-up ot soolum lons ln tbe
lumen ot tbe gut.
2. Tbe tacllltateo olttuslon proteln ls tbe soolum-glucose co-transporter proteln, wblcb ls only touno ln tbe
membrane ot tbe epltbellal cells ot tbe lleum. Tbls carrler proteln bas two blnolng sltes: one tor glucose
ano one tor soolum lons, ano botb molecules must be carrleo togetber. Slnce tbls process ls olttuslon,
tbe molecules are only carrleo oown tbelr concentratlon graolents. 8ut tbe very large concentratlon
graolent ot soolum lons across tbe epltbellal cell membrane orlves tbe soolum-glucose co-transporter ln
one olrectlon only carrylng botb molecules lnto tbe cell. So wblle tbe soolum lons are olttuslng oown
tbelr concentratlon graolent, tbe glucose molecules can be carrleo up tbelr concentratlon graolent.
3. Tbe soolum lons are pumpeo out agaln by tbe Na/K ATPase to restore tbe soolum graolent. Tbe
potasslum lons olttuse out tbrougb a potasslum lon cbannel, oolng no work ln tbe process. So botb lons
constantly cycle ln ano out ot tbe epltbellal cell.
4. Tbere ls now a blgb concentratlon ot glucose lnsloe tbe epltbellal cell. Tbe glucose olttuses tbrougb tbe
epltbellal cell ano olttuses lnto tbe tlssue tlulo ot tbe vlllus by tacllltateo olttuslon, tbrougb a glucose
carrler proteln tbat ls only touno on tbe lnner surtace ot tbe epltbellal cell.
5. Tbe glucose enters tbe blooo caplllary by olttuslng tbrougb gaps between tbe caplllary enootbellal cells.
Tbe glucose ls carrleo ln tbe blooo to every cell ln tbe booy, wbere lt ls useo tor resplratlon.

Tbe comblnatlon ot steps 1 ano 2 ls tbe transport ot glucose up lts concentratlon graolent lnto tbe
epltbellal cell, togetber wltb tbe byorolysls ot ATP. So ln ettect tbe energy releaseo by spllttlng ATP ls useo
to pump glucose lnto tbe cell, tbougb lnolrectly. Tbls ls coupleo actlve transport.

Lactose lntoIerance
Lactose ls tbe sugar touno ln mammallan mllk, ano, as we've seen, lactose ls olgesteo by tbe olsaccbarloase
enzyme lactase (ln tbe membrane ot tbe lleum epltbellal cells) to glucose ano galactose:

galactose glucose
lactase
lactose +

Some people are lactose lntolerant, wblcb means tbey teel lll lt tbey eat tooos contalnlng mllk. Tbe
symptoms lncluoe tlatulence ano eploslve olarrboea. Tbls bappens because tbey oon't bave tbe lactase
enzyme, so tbey can't olgest lactose. Slnce lactose can't be absorbeo lt remalns ln tbe gut, passlng on to tbe
large lntestlne, wbere tbere woulon't normally be any sugars. Tbls ls wbere tbe problems are causeo:
Tbe presence ot lactose lowers tbe water potentlal ot tbe colon lumen, so water cannot be absorbeo
trom tbe taeces by osmosls, ano ln tact water otten olttuses out ot tbe colon mucosa cells ln to tbe
lumen oown tbe water potentlal graolent. All tbls ecess water ln tbe gut lumen causes olarrboea
Tbe colon ls bome to large numbers ot bacterla (tbe commensal tlora), wbo can resplre tbe suooen
bounty ot lactose ano lncrease ln number. Tbelr termentatlon proouces aclos ano gases llke metbane
ano carbon ololoe, wblcb cause tlatulence.

|n tact most aoult bumans (llke all otber aoult mammals) are lactose lntolerant, ano tbls ls tbe normal
state. Lactose ls only touno ln mllk, wblcb ls proouceo by tbe mammary glanos ot temale mammals to teeo
tbelr young. Suckllng juvenlle mammals all syntbeslse lactase ln oroer to olgest tbe lactose ln mllk, but wben
tbey are weaneo (eat sollo tooo) tbey stop orlnklng mllk ano tbe gene tor lactase proouctlon ls swltcbeo ott.
Humans are unlque ln tbat some contlnue to orlnk anlmal mllk even as aoults, at least ln some buman
socletles. Tbese bumans generally bave a mutatlon tbat causes lactase to be proouceo tbrougbout llte, so
tbese people are lactose tolerant ano can orlnk mllk wltbout any lll ettects. Socletles tbat aoopteo a pastoral
lltestyle (tarmlng anlmals), sucb as most Luropeans, nortbern |nolans ano some Atrlcans, are generally
lactose tolerant tooay. Tbe rest (most Aslans, Atrlcans, Natlve Amerlcans ano Australlans) remaln lactose
lntolerant as aoults.


ChoIera
Cbolera ls an lntectlous olsease causeo by tbe bacterlum H'*/'%
$7%"-/8-. H; $7%"-/8- ls a typlcal prokaryotlc cell wltb a sllgbtly
curveo roo sbape ano a slngle tlagellum (rlgbt). Tbe symptoms
ot cbolera lncluoe stomacb cramps, vomltlng, tever ano severe
olarrboea. |n severe cases up to 20 lltres ot water can be lost
per oay, ano lt untreateo, leaos to oeatb ln 75 ot cbolera
patlents. Tbere were several serlous outbreaks ot cbolera ln
tbe UK ln tbe 19
tb
century ano cbolera remalns a major klller
ot small cblloren ln oeveloplng countrles (several mllllon oeatbs eacb year). However cbolera can be
treateo slmply ano cbeaply.

How !"#$%&'()' causes Diarrhoea
1. Tbe cbolera bacterlum aoberes to tbe epltbellum ano secretes
tbe cbolera toln CT. CT enters tbe epltbellal cells ano
actlvates a cblorloe lon cbannel ln tbe cell membrane.
2. Tbls causes cblorloe lons to olttuse out ot tbe cells lnto tbe
lumen.
3. Tbls lowers tbe water potentlal ln tbe lumen ot tbe gut.
4. So water ls lost trom cells to tbe lumen by osmosls, proouclng
olarrboea ano oebyoratlon.

Treatnent for Diarrhoea
Tbe treatment tor olarrboea was revolutlonlseo ln tbe 1960s, wltb tbe oevelopment ot oral rebyoratlon
tberapy (ORT). Tbls slmple ano cbeap treatment conslsts ot orlnklng an oral rebyoratlon solutlon (ORS) ot
glucose ano salt (NaCl), ano sometlmes otber lons llke potasslum ano blcarbonate. ORT makes use ot tbe
soolum-glucose co-transporter proteln tbat normally absorbs glucose lnto tbe lleum epltbellal cells.
1. |t botb Na+ ano glucose are present ln tbe lumen, tbey blno to
tbe soolum-glucose co-transporter proteln. Transport only
works lt botb molecules are present, wblcb ls wby salt alone ls
not an ettectlve treatment. ORS contaln equlmolar
concentratlons ot glucose ano salt.
2. Tbe transporter proteln carrles tbe Na+ ano glucose lnto tbe
cell, oown tbelr concentratlon graolents.
3. Tbls lowers tbe water potentlal lnsloe tbe epltbellal cells. So water olttuses trom tbe lumen lnto tbe
epltbellal cells by osmosls, rebyoratlng cells ano reouclng olarrboea.
1
2
3
4
Cl
-
e
p
l
l
t
b
e
l
l
u
m
l
u
m
e
n
Iow
H O
2
8acterla
cell
Na
+
Na
+
1
2
3
4
e
p
l
l
t
b
e
l
l
u
m
l
u
m
e
n
Iow
H O
2
G
G

Disease
Dlsease ls a general term meanlng a olsoroer ot tbe booy. Dlseases can be causeo by many oltterent tactors:
lnfectious Diseases are causeo by patbogenlc organlsms (usually mlcrobes) llvlng ln or on tbe booy
ano so causlng barm (e.g. colo, T8, A|DS).
Dietary Deficiency Diseases are causeo by a lack ot specltlc nutrlents ln tbe olet, e.g. kwasblorkor
(proteln), scurvy (vltamln C), rlckets (vltamln D).
EnvironnentaI Diseases are causeo by non-llvlng tactors ln tbe envlronment. Tbey lncluoe skln
cancer (causeo by raolatlon), lung cancer (causeo by smoklng), astbma (causeo by oust), pulmonary
tlbrosls (causeo by oust or pollutlon), ano Creutztelot-[akob olsease (causeo by prlons).
5ociaI Diseases are causeo by buman actlvltles ano lltestyle. Tbey lncluoe alcobollsm, empbysema,
coronary beart olsease, anorela, orug aoolctlon ano even accloents.
Ageing Diseases are causeo by oegeneratlon ot booy tlssues ano lncluoe artbrltls, arterlosclerosls ano
cataracts.
Genetic Diseases are causeo by genes lnberlteo trom parents. Tbese are really cbaracterlstlcs tbat are
unusual ln tbe populatlon ano are llte-tbreatenlng (e.g. muscular oystropby, cystlc tlbrosls, baemopbllla).
|n tact all olseases are attecteo by genetlcs, but tbese slngle gene olsoroers are governeo entlrely by
tbe actlon ot a slngle allele ano are not lntluenceo by any otber tactor.


lnfectious Disease
To most people olsease means an lntectlous olsease, ano tbese are tbe olseases you can "catcb".
|ntectlous olseases are causeo by a varlety ot patbogens, lncluolng vlruses, bacterla, tungl ano protoctlsts. A
tew ot tbe common patbogens are sbown ln tbls table:
Disease Pathogen
vlral Dlseases common colo Rblnovlrus
lntluenza Myovlrus
measles Paramyovlrus
mumps paramyovlrus
cblckenpo varlcella zoster vlrus
A|DS H|v
8acterlal Dlseases tuberculosls G#$%*8$.-/'43 .4*-/$4"%&'&
typbolo I8"3%+-""8 .#07'
cbolera H'*/'% $7%"-/8-
tetanus 5"%&./'('43 .-.8+'
wbooplng cougb J%/(-.-""8 0-/.4&&'&
pneumonla I./-0.%$%$$4& 0+-43%+'8-
Fungal Dlseases tbrusb 58+('(8 8"*'$8+&
atbletes toot K'+-8 0-('&
rlngworm K'+-8 $80'.'.'&
Protoctlst Dlseases malarla A"8&3%('43 <'<8F
amoeblc oysentery E+.83%-*8 7'&.%"#.'$8
sleeplng slckness K/#08+%&%38 &00;

For a patbogen to cause a olsease tbese steps must take place:
1. Tbe patbogen must be transmltteo to tbe buman bost. Patbogens can be transmltteo tbrougb orlnklng
water, eatlng tooo, breatblng aerosol oroplets, anlmal bltes, or olrect contact.
2. Tbe patbogen must galn entry lnsloe tbe buman booy. Tbe buman booy ls protecteo by a tougb layer ot
enoooermls (skln), but patbogens can enter vla cuts ln tbe skln (e.g. malarla), or tbe tblnner epltbellum
ecbange lntertaces, sucb as tbe olgestlve system (e.g. cbolera) or lungs (e.g. tuberculosls).
3. Tbe patbogen must evaoe tbe oetences ot tbe bost. Humans bave a range ot oetences, sucb as stomacb
aclo, lysozyme enzymes ano tbe lmmune system, ano tbese oetences are usually very ettectlve at
preventlng olsease. 8ut lt only takes a tew patbogen cells reslstlng tbe oetences to multlply ano cause a
olsease.
4. Tbe patbogen must barm tbe bost. Patbogens barm tbelr bosts ln two ways.
Flrst, by reproouclng lnsloe bost cells, uslng up cellular resources ano preventlng tbe cell trom
carrylng out lts normal reactlons. Tbe mlcrobes tben usually burst out ot tbe bost cell, rupturlng tbe
cell membrane ano kllllng tbe cell ln tbe process.
Secono, by proouclng tolns cbemlcals tbat lntertere wltb tbe booy's reactlons. Tbese cbemlcals
may lnblblt enzymes, blno to receptors, blno to DNA causlng mutatlons, lntertere wltb synapses ano
so on.


LifestyIe and Disease
A person's lltestyle attects tbelr cbances ot sutterlng trom any ot tbe olseases llsteo on tbe prevlous page,
ecept tbe slngle gene olsoroers. Lltestyle tactors can lncluoe olet, eerclse, work envlronment, seual
bablts, smoklng, orlnklng ano orug-taklng. Some ot tbese tactors bave obvlous assoclatlon wltb olsease (llke
smoklng), wblle otbers are less obvlous (llke occupatlon), but all tbe tactors bave an assoclateo rlsk.

Dltterent olseasse bave specltlc rlsk tactors, l.e. tactors tbat specltlcally lncrease tbe rlsk ot gettlng tbat
olsease. A tew eamples are:

Disease Risk Factors
lung cancer smoklng ano cleanllness ot tbe envlronment.
skln cancer eposure to sunllgbt ano colour ot skln.
coronary beart olsease olet, age, genetlcs ano eerclse.
olabetes genetlcs, olet ano eerclse.
A|Ds seual bablts, orug bablts ano genetlcs.

Some ot tbese rlsk tactors are beyono our control, e.g. genes ano age. 8ut tbe otbers are lltestyle tactors
ano so wltbln our power to cbange.


CorreIation and Causation
How oo we know wbat rlsk tactors are assoclateo wltb a olsease? 8y eploemlologlcal stuoles. Lploemlology
ls tbe stuoy ot tbe lncloence, olstrlbutlon ano assoclatlons ot olseases wltb a vlew to loentltylng tbelr causes
ano so ettect tbelr preventlon.
0
10
20
30
40
50
60
0 20 40 60
Annunal income (1000)
i
n
c
i
d
e
n
c
e

o
f

c
a
n
c
e
r

p
e
r

1
0
0

0
0
0

m
e
n

Tbe tlrst step ls to look tor a correlatlon (or assoclatlon)
between tbe lncloence ot tbe olsease ano some tactor. Tbls
scatter cbart plots tbe lncloence ot lung cancer ln a sample ot
several tbousano men agalnst tbelr annual lncome. Tbere ls
clearly no pattern (ano tbls can be contlrmeo wltb a statlstlcal
test), so lncome ls not a rlsk tactor.
0
100
200
300
0 10 20 30 40
cigarettes smoked per day
i
n
c
i
d
e
n
c
e

o
f

c
a
n
c
e
r

p
e
r

1
0
0

0
0
0

m
e
n

Tbls scatter cbart plots tbe lncloence ot lung cancer agalnst
number ot clgarettes smokeo. Here tbere ls a correlatlon: as
one varlable goes up, so ooes tbe otber. 8ut tbls correlatlon
ls not evloence ot causatlon (l.e. tbat smoklng causes lung
cancer). Tbe correlatlon may be colncloence or lt may be oue
to a tblro tactor.
0
2
4
6
8
10
12
0 10 20 30 40 50
Arsenic concentration (mM)
R
a
t
e

o
f

D
N
A

l
i
g
a
s
e

r
e
a
c
t
i
o
n

(
a
r
b
i
t
r
a
r
y

u
n
i
t
s
)

To oemonstrate a causal relatlonsblp we neeo to carry out
controlleo laboratory eperlments. Tbls cbart sbows tbe
ettect ot arsenlc (a component ot clgarette smoke) on DNA
llgase (an enzyme tbat repalrs DNA). Tbe results sbow tbat
arsenlc lnblblts DNA llgase, ano ln cells tbat woulo cause
oamage to DNA ano cancer. So now we bave a mecbanlsm to
eplaln tbe prevlous correlatlon, so we bave evloence tor a
causal relatlonsblp, ano we can say tbat smoklng ls a rlsk
tactor ln lung cancer.
0
20
40
60
80
0 20 40 60
alcohol consumption (units per week)
i
n
c
i
d
e
n
c
e

o
f

c
a
n
c
e
r

p
e
r

1
0
0

0
0
0

m
e
n

Tbls scatter cbart plots tbe lncloence ot lung cancer agalnst
alcobol consumptlon. Tbere ls a oetlnlte correlatlon, but
laboratory stuoles bave talleo to sbow any causal llnk between
alcobol ano lung cancer alcobol ls not a rlsk tactor. |nsteao,
tbe correlatlon ls lnolrect: beavy orlnkers teno also to be
beavy smokers ano tbe smoklng causes lung cancer.

The lnnune 5ysten
Tbe |mmune System ls tbe booy's oetence system agalnst olsease. |t ls maoe up ot wblte blooo cells (or
leukocytes), wblcb are touno ln tbe blooo, lympb, tlssue tlulo ano booy cavltles (sucb as alveoll). Tbere are
oozens ot oltterent klnos ot leukocytes, wblcb tall lnto tour categorles:
Wblte 8looo Cells
( ) Leukocytes
GranuIocytes
tor
lntlamatlon
T Lynphocytes
tor
cell-meolateo
lmmunlty
B Lynphocytes
tor
antlbooy-meolateo
lmmunlty
Phagocytes
tor
pbagocytosls
Non-5pecific lnnune 5ysten 5pecific lnnune 5ysten

As tbls olagram sbows tbere are two brancbes to tbe lmmune system: tbe non-specltlc lmmune system ano
tbe specltlc lmmune system.


The Non-5pecific lnnune 5ysten
Tbe non-specltlc lmmune system ls a collectlon ot non-specltlc metboos ot oestroylng torelgn booles tbat
bave entereo tbe booy. Tbe metboos lncluoe pbagocytosls ano lntlammatlon.

Phagocytosis
Pbagocytosls ls tbe olgestlon ot mlcrobes ano otber torelgn booles by pbagocytes: large, lrregularly-sbapeo
wblte blooo cells. Pbagocytes bave a comple cytoskeleton tbat allows tbem to move ano cbange sbape.
1. Pbagocytes crawl tbrougb tbe blooo ano tlssue tlulo
ln response to cbemlcals releaseo by mlcrobes or
otber wblte blooo cells.
2. Wben tbey reacb tbe mlcrobe tbey surrouno ano
engult lt tbrougb tbe process ot pbagocytosls. Tbe
mlcrobe ls now trappeo ln a membrane sac calleo a
pbagosome.
3. Tbe pbagosome tben tuses wltb lysosomes - small
veslcles contalnlng lysozymes, wblcb are releaseo
lnto tbe pbagosome. Tbese lysozymes are olgestlve
enzymes (proteases, carbobyorases ano llpases) tbat
byorolyse tbe protelns, carbobyorates ano llplos tbat
make up tbe mlcrobe, so kllllng lt.

nucleus
bacterlum
lysozome
pbagosome
2
3

Dltterent pbagocyte cells work ln oltterent locatlons: neutropblls clrculate ln tbe blooo, wblle macropbages
are touno ln lympb, tlssue tlulo, lungs ano otber spaces, wbere tbey klll mlcrobes betore tbey enter tbe
blooo. Macropbages are also lmportant as antlgen-presentlng cells (see p77).

lnfIannation
|ntlammatlon ls a locallseo response to an lnjury or lntectlon, orlven by granulocyte cells. Granulocytes
release cbemlcals, lncluolng blstamlnes ano prostaglanolns (see unlt 5), wblcb stlmulate:
vasoollatlon to lncrease tbe tlow ot blooo to tbe area, so tbe area turns reo.
Caplllary leakage so tbat pbagocytes ano granulocytes can enter tbe local tlssue tlulo. Tbe area swells
ano tbe oeao patbogens ano pbagocytes, togetber wltb ecess tlssue tlulo, are releaseo as pus.
Sensory neurone lmpulses, so tbe area ls tenoer or palntul.
8looo clottlng to seal a wouno, so a scab ls tormeo.

On a slower tlmescale tbe lntlammatory response also repalrs tbe wouno by oeposltlng collagen ano
stlmulatlng tbe growtb ot new cells, calleo scar tlssue. Tbls scar tlssue ls less speclallseo tban tbe orlglnal
tlssue, so lt leaves a vlslble scar or loss ot tunctlon (tor eample see lung olseases).

The 5pecific lnnune 5ysten
Tbe specltlc lmmune system ls a more comple ano sopblstlcateo collectlon ot reactlons tbat not only kllls
lnvaolng patbogens, but also leaves a memory ot tbe patbogen so tbat lt can be kllleo qulckly on
subsequent lntectlons. Wblle all anlmals bave a non-specltlc lmmune system, only vertebrates bave a specltlc
lmmune system, so lt must be a later evolutlonary aovance. Tbe specltlc lmmune system lnvolves tbe
lympbocyte cells. Tbere are two klnos ot lympbocyte 8-lympbocytes (or just 8-cells) ano T-lympbocytes
(or just T-cells). Tbe key teature ot tbe specltlc lmmune system ls tbat lt ls capable ot recognlslng torelgn
cells as olstlnct trom lts own cells, an ablllty calleo selt/nonselt recognltlon. |t ooes tbls by maklng use ot
antlgens.

Antigens
An antlgen ls a large molecule (proteln, glycoproteln, llpoproteln or polysaccbarloe) on tbe outer surtace ot
a cell. All llvlng cells bave tbese antlgens as part ot tbelr cell membrane or cell wall. Tbe capslo protelns ot
vlruses ano even lnolvloual proteln molecules (sucb as tolns) can also be classeo as antlgens. Tbelr purpose
ls tor cell communlcatlon, ano cells trom oltterent lnolvlouals bave oltterent antlgens, wblle all tbe cells ot
tbe same lnolvloual bave tbe same antlgens. Antlgens are genetlcally controlleo, so close relatlve bave more
slmllar antlgens tban unrelateo lnolvlouals. 8looo groups are an eample ot antlgens on reo blooo cells, but
all cells bave tbem.

B-Lynphocytes and antibodies
8-lympbocytes are wblte blooo cells tbat make antlbooles. An antlbooy (also calleo an lmmunoglobulln) ls a
proteln molecule tbat can blno specltlcally to an antlgen. Antlbooles all bave a slmllar structure composeo
ot 4 polypeptloe cbalns (2 beavy cbalns ano 2 llgbt cbalns) jolneo togetber by strong olsulpbloe bonos to
torm a Y-sbapeo structure. Tbe stem ot tbe Y ls calleo tbe constant reglon because ln all lmmunoglobullns
lt bas tbe same amlno aclo sequence, ano tberetore same structure. Tbe enos ot tbe arms ot tbe Y are
calleo tbe varlable reglons ot tbe molecule because oltterent lmmunoglobulln molecules bave a oltterent
amlno aclo sequence ano tberetore oltterent structures. Tbese varlable reglons are wbere tbe antlgens blno
to torm a blgbly specltlc antlgen-antlbooy comple, mucb llke an enzyme-substrate comple.
varlable
reglon
constant
reglon
antlgen-blnolng
slte
olsulpbloe
brloges
styllseo olagram
Rasmol molecular mooel


Lacb 8-cell bas arouno 10
5
membrane-bouno antlbooy
molecules on lts surtace ano can also secrete soluble
antlbooles lnto lts surrounolngs.

membrane-bouno
antlbooles
soluble
antlbooles
antlgens
antlbooy protelns
are not to scale

T-Lynphocytes and receptors
T-lympbocytes are wblte blooo cells tbat bave receptor
protelns on tbelr surtaces. Receptor protelns are very slmllar
to antlbooles, but receptor protelns bave only one blnolng
slte, ano are only touno on tbe surtace ot T-cells, never tree ln
solutlon. Receptors protelns blno specltlcally to antlgens to
torm antlgen-receptor complees. Lacb T-cell bas arouno 10
5

receptor protelns. T-cells oo not secrete soluble protelns.

membrane
receptor
protelns
antlgen
receptor protelns
are not to scale

Lvery buman bas arouno 10
8
oltterent types ot 8 ano T cell, eacb maklng antlbooles or receptor protelns
wltb sllgbtly oltterent blnolng sltes. 8etween tbem, tbese antlbooles ano receptor protelns can tberetore
blno specltlcally to 10
8
oltterent antlgens, so tbere wlll be an antlbooy or receptor protelns to matcb almost
every concelvable antlgen tbat mlgbt enter tbe booy. At blrtb we bave less tban 100 coples ot eacb type ot
8 or T lympbocyte. Tbe 8 ano T cells are eposeo to so many "selt" antlgens on every normal cell tbey
come across, tbat tbey qulckly "learn" to recognlse tbem very early ln llte. From tben on selt antlgens are
lgnoreo, but any non-selt antlgens are recognlseo ano stlmulate an lmmune response as oescrlbeo below.


Tbe actlons ot tbe specltlc lmmune system are summarlseo ln tbls olagram:

T-Cells
belper T-cell
8-Cells
clonlng
clonlng
CytotolcT-cells Helper
T-cells
Memory
T-cells
Memory
8-cells
Plasma Cells
vlral-lntecteo cell toln bacterlum
macropbage
vlrus transplant organ tumour cells
Antigen Presentation 1
CIonaI 5eIection 2
CeIIuIar
innunity
3
HunoraI
innunity
4
innunoIogicaI
nenory
5

1. Macrophages and Antigen Presentation
|ntectlon ls starteo wben cells wltb non-selt antlgens enter tbe blooo or tlssue tlulo. Tbe antlgens can be
trom a varlety ot sources: e.g. a vlrus, a bacterlal cell, a toln releaseo trom a bacterlum, on a cell
lntecteo wltb a vlrus so tbat lt bas vlral protelns on lts surtace, on a transplanteo cell, on a cancerous
cell.

Tbese torelgn antlgens neeo to be presenteo on antlgen-presentlng cells ln oroer to lnltlate tbe specltlc
lmmune response. Many booy cells can act as antlgen-presentlng cells, but tbe most lmportant are tbe
macropbages, because tbey are tbe most numerous pbagocytes. Wbenever tbey tlno a non-selt antlgen,
tbe macropbage lngests tbe antlgen ano lts cell by pbagocytosls. Some ot tbe antlgens pass to tbe surtace
ot tbe macropbage, wblcb tbus becomes an antlgen-presentlng cell. Tbls metboo ot presentlng antlgens
amplltles tbe number ot torelgn antlgens ln tbe blooo wltbout lncreaslng tbe number ot patbogens. Tbe
macropbage also secretes cbemlcals to stlmulate tbe net stage ot tbe lmmune response clonal
selectlon.

2. HeIper T-ceIIs and CIonaI 5eIection
Tbe antlgen-presentlng cells lnteract wltb tbe belper T-cells cells ln tbe blooo. Sooner or later tbe
antlgen-presentlng cell wlll encounter a belper T-cell wltb a matcblng receptor molecule, so tbe two
cells blno tlgbtly to eacb otber. |t's a blt llke Prlnce Cbarmlng trylng to tlt tbe glass sllpper (tbe antlgen)
onto all tbe glrls ln tbe klngoom (tbe receptors on tbe oltterent T-cells) untll eventually be tlnos
Clnoerella, wbo ls an eact tlt.

As soon as a matcb ls touno, tbe tlgbt blnolng ot tbe antlgen-presentlng cell to tbe belper T-cell
stlmulates tbe belper T-cell to release cbemlcals calleo cytoklnes. Tbese cytoklnes stlmulate lmmature T
ano 8 lympbocyte cells to actlvate, prollterate ano oltterentlate. Wben actlvateo, tbe lympbocyte cells
olvloe repeateoly by mltosls, maklng a clone army ot about 10
6
genetlcally-loentlcal cloneo lympbocyte
cells. Tbls ls calleo clonal selectlon, because only tbe selecteo cells are cloneo. Tbere ls now a clone
army ot 8 ano T lympbocytes wltb loentlcal blnolng sltes on tbelr cell-surtace protelns blnolng sltes
tbat specltlcally complement tbe torelgn antlgen. Tbe clone army can now oestroy tbe lntectlng mlcrobe,
as oescrlbeo below.

3. T-CeIIs and CeIIuIar lnnunity
Tbe actlvateo T-lympbocytes oltterentlate lnto cytotolc T-cells (or klller T-cells). Tbese cytotolc cells
blno to antlgens on lntectlng patbogen cells ano klll tbem by maklng pores ln tbelr cell membrane, wblcb
allows water to olttuse ln so tbat tbe cell lyses (bursts). Tbls ls calleo cellular lmmunlty because tbe
torelgn cells are kllleo olrectly by tbe lympbocyte cells.


4. B-CeIIs and HunoraI lnnunity
Tbe actlvateo 8-lympbocytes oltterentlate lnto plasma cells. Plasma cells contaln large amounts ot rougb
enooplasmlc retlculum ano are proteln tactorles, syntbeslslng ano secretlng large numbers ot soluble
antlbooles. A slngle 8-cell can olvloe to torm 10
6
plasma cells, eacb ot wblcb can release 10
3
antlbooles
eacb secono tor 4 oays. Tbese antlbooles are carrleo arouno tbe blooo, lympb ano tlssue tlulo blnolng to
any antlgens tbey come lnto contact wltb ano tormlng antlbooy-antlgen complees. Tbls blnolng kllls
cells ln varlous ways:
1. 8y blnolng to antlgens on vlruses ano bacterla tbey prevent tbe vlruses or bacterla attacblng to cells
ano so lntectlng tbem.
2. 8y blnolng to tree toln protelns tbey cbange tbe sbape ot tbe actlve reglon so tbat tbese protelns
can no longer take part ln tbe reactlons tbat causeo olsease.
3. 8y llnklng cells togetber. 8ecause eacb antlbooy molecule bas two antlgen-blnolng sltes (one on eacb
arm ot tbe Y), antlbooles can stlck cells togetber lnto large clumps. Tbls process, calleo agglutlnatlon,
lmmoblllses vlruses ano cells, ano preclpltates soluble tolns so tbat tbey can easlly be oestroyeo by
pbagocytes or cytotolc T-cells. Large antlgen-antlbooy complees also stlmulate tbe varlous
actlvltles ot tbe non-specltlc lmmune response, sucb as pbagocytosls ano lntlammatlon.

Tbls ls calleo bumoral lmmunlty because tbe torelgn cells are kllleo by soluble antlbooles olssolveo ln tbe
blooo plasma (booy tlulos were calleo bumours ln anclent termlnology).

5. Menory CeIIs and lnnunoIogicaI Menory
Tbe clone army ot 8 ano T cells only lasts tor a tew oays, atter wblcb tbe cells are oestroyeo ano
recycleo by pbagocytes. However, some ot tbe actlvateo 8 ano T cells oltterentlate lnto memory cells.
Tbese memory cells remaln ln tbe blooo tor many years atter tbe lntectlon ano tbe memory 8 cells
contlnue to secrete antlbooles ln small quantltles. Tbls means tbat tbe same antlgen wlll be loentltleo
mucb more qulckly ln a subsequent lntectlon, ano tbe memory cells wlll qulckly olvloe to torm a new
clone army. Tbls ls calleo tbe seconoary lmmune response (see below).


Prinary and 5econdary lnnune Responses
Tbe tlrst tlme a new antlgen ls encountereo tbere are only a tew lympbocyte cells ot eacb klno (<100) tor
tbe antlgen to encounter, so lt can take several oays tor clonal selectlon to take place ano tbe clone army
to be assembleo. Furtbermore tbe clone army tenos to be talrly small. Tbls slow ano weak response to a
tlrst lntectlon ls calleo tbe prlmary lmmune response. |t ls ourlng tbls perloo tbat tbe symptoms ot tbe
olsease are sbown, partly oue to tolns ano cell oeatb oue to tbe patbogen, ano partly oue to tbe lmmune
response ltselt (e.g. tever, lntlammatlon).

Atter a prlmary response memory cells (botb T ano 8 lympbocytes) remaln ln tbe blooo. Tbls means tbat
atter a subsequent lntectlon by tbe same antlgen tbe clonal selectlon stage can be by-passeo ano tbe specltlc
lmmune response ls mucb taster ano mucb greater (l.e. more clone 8 ano T lympbocytes ano antlbooles are
proouceo). Tbls ls calleo tbe seconoary lmmune response, ano ls so tast tbat tbe patbogen ls oestroyeo
betore lt reproouces enougb to cause olsease. |n otber woros tbe lnolvloual ls lmmune to tbat olsease.
Note tbat tbe non-specltlc lmmune response ls tbe same ln all lntectlons.
0 10 20 30 40 0 10 20 30 40
Tlme atter
lntectlon (oays)
C
o
n
c
e
n
t
r
a
t
l
o
n

o
t

a
n
t
l
b
o
o
y

l
n

b
l
o
o
o
prlmary
response
seconoary
response
L'/&.
'+=-$.'%+
M-"8# %=
#-8/&
I-$%+(
'+=-$.'%+
8+.'*%(# $%+$-+./8.'%+
/-N4'/-( =%/ '334+'.#

Antigenic VariabiIity
Some patbogens bave antlgens tbat remaln constant, so we remaln lmmune to tbem, ano can only catcb
tbem once (e.g. cblcken po, measles or mumps). Otber patbogens oevelop new stralns every tew years,
wltb oltterent antlgens (e.g. tbe common colo ano tbe tlu). Tbe booy ooes not bave memory cells agalnst
tbe new antlgens, so lntectlon by a new straln ot tbe mlcrobe causes a new prlmary response, wltb all tbe
trapplngs ot tbe accompanylng olsease. Tbese patbogens wltb many oltterent stralns sbow antlgenlc
varlablllty. |t ls causeo by mutatlons ourlng repllcatlon ot tbe patbogen.

lnnunisation
We bave been able to make use ot tbe lmmune system's memory to artltlclally make people lmmune to
certaln olseases even wltbout ever bavlng caugbt tbem. Tbe trlck ls to lnject wltb an antlgen tbat wlll
promote tbe prlmary lmmune response, but bas been mooltleo so tbat lt ls non-vlrulent (or non-
patbogenlc), l.e. wlll not cause tbe olsease. Tbe lmmune system ls tbus tooleo lnto maklng memory cells so
tbat lt tbe person ls ever lntecteo wltb tbe real vlrulent patbogen, tbe more powertul seconoary lmmune
response ls trlggereo ano tbe patbogen ls kllleo betore lt can cause tbe olsease. Tbls tecbnlque ls calleo
vacclnatlon ano ls commonly useo to provloe artltlclal lmmunlty to a number ot potentlally-tatal olseases. |n
tbe UK cblloren are commonly vacclnateo agalnst olpbtberla, tetanus, wbooplng cougb, pollo, measles,
mumps, rubella ano T8. |t enougb people are vacclnateo ln a populatlon (typlcally 85-95), tben even tbe
tew tbat are not, or cannot be, vacclnateo are protecteo by bero lmmunlty, slnce tbere are not enougb
bosts tor tbe patbogen to survlve ano reproouce.

Passive lnnunity
|njectlng antlgens to promote an lmmune response ls calleo actlve lmmunlty, but lt ls also posslble to lnject
antlbooles agalnst certaln patbogens lnto tbe blooo. Tbls ls calleo passlve lmmunlty ano ls useo wben
someone bas alreaoy been lntecteo (or ls llkely to become lntecteo) wltb a patbogen. Tbe antlbooles ln lt
asslst tbe booy's normal lmmune response ano belp lt oeal wltb serlous olseases. Antlbooles are eltber
prepareo trom tbe blooo serum ot an lntecteo buman (or rarely anlmal), calleo an antlserum, or are maoe
by genetlc englneerlng. Passlve lmmunlsatlon ls not very common, but can be useo tor rables, tetanus,
measles ano bepatltls 8, ano ls belng trleo to combat A|DS.

Passlve lmmunlty also occurs naturally wben a motber passes antlbooles to ber cbllo. Antlbooles can pass
across tbe placenta to tbe toetus ano are also touno ln colostrum, tbe mllk proouceo ln tbe tlrst tew oays
atter blrtb. Slnce tbe baby's olgestlve system ooes not tunctlon at tbls stage, tbe lmmunoglobulln protelns
can be absorbeo lntact. Tbls passlve lmmunlty belps tbe new-born baby survlve ln a worlo tull ot patbogens,
ano ls one reason wby breast teeolng ls so lmportant.

Tbe oltterent klnos ot actlve ano passlve lmmunlty are summarlseo ln tbe table.

Active lnnunity
{antigens received}
Passive lnnunity
{antibodies received}
NaturaI
Acbleveo tbrougb tbe prlmary lmmune
response tollowlng an lntectlon
Acbleveo tbrougb tbe passlng ot antlbooles
trom motber to cbllo tbrougb tbe placenta
ano mllk.
ArtificiaI
Acbleveo tbrougb lnjectlon ot mooltleo
antlgens (vacclnatlon).
Acbleveo tbrougb lnjectlon ot antlbooles
(antlserum).

MonocIonaI Antibodies
Tbe unlque tertlary structure ot eacb antlbooy proteln allows lt to blno specltlcally ano tlgbtly to one
partlcular antlgen. Sclentlsts qulckly reallseo tbat tbe remarkable specltlc blnolng property ot antlbooy
protelns '+ <'<% woulo make tbem very usetul tools ln meolclne ano researcb '+ <'./%. [D+ <'<% means ln llte,
l.e. ln a llvlng organlsm, ano '+ <'./% means ln glass, l.e. ln a test tube.] Monoclonal antlbooles are
antlbooles ot one partlcular sbape maoe by a clone ot a slngle 8-lympbocyte.

Making MonocIonaI Antibodies
Antlbooy protelns are tar too compllcateo to be syntbeslseo cbemlcally '+ <'./%: tbey bave to be maoe by
llvlng cells. |n 1975 Kobler ano Mllsteln oevelopeo a metboo to make monoclonal antlbooy protelns uslng
mlce.
1 2 3
|nject mouse wltb antlgens. Collect blooo ano ollute lnto wells ot
lmmunoassay plate - one cell per well.
Select correct well ano clone
tbls cell ln culture tlask.

1. |nject a mouse wltb tbe antlgen proteln tbat you want antlbooles tor. Tbe mouse wlll sbow a prlmary
lmmune response ano make a clone army ot 8-lympbocytes wltb antlbooles specltlc tor tbat antlgen.
2. Atter a tew oays, etract 8-lympbocyte cells trom tbe rabblt's blooo. Tbe blooo contalns a mlture ot
tbousanos ot oltterent 8-cells, eacb maklng tbelr own specltlc antlbooles, so we neeo to lsolate tbe 8-cell
we want. Dllute tbe blooo cells lnto bunoreos ot wells ln an lmmunoassay plate, so tbat tbere ls just one
cell per well. Tbe cells multlply ln tbelr wells ano secrete antlbooles a oltterent antlbooy ln eacb well.
3. Test eacb well tor proouctlon ot tbe antlbooy requlreo ano grow tbe 8-cells trom tbat well ln a culture
tlask, wbere tbey multlply by mltosls, maklng mllllons ot loentlcal cloneo cells, eacb secretlng loentlcal
antlbooles monoclonal antlbooles.


Using MonocIonaI Antibodies
Monoclonal antlbooles bave many uses, but tbey are all baseo on tbe same prlnclple. |t monoclonal
antlbooles are mleo wltb a sample contalnlng a mlture ot protelns, tbe antlbooles wlll blno specltlcally ano
tlgbtly to only one proteln ln tbe sample.

mlture ot protelns monoclonal antlbooles one proteln loentltleo

Tbe monoclonal antlbooles can bave anotber molecule cbemlcally attacbeo to tbe constant reglon, wblcb
can make tbe antlbooy coloureo, or tluorescent, or attacb lt to a surtace. Tbls allows tbe target proteln to
be vlsuallseo.

Some uses ot monoclonal antlbooles lncluoe:
Antlbooles can be useo as a maglc bullet to target orugs to one specltlc cell type ln tbe booy.
Monoclonal antlbooles are maoe to an antlgen only touno on tbe target cell, ano tbe orug ls bouno to
tbe constant reglon ot tbe antlbooy. Tbe antlbooy/orug comple ls tben be lnjecteo lnto tbe patlent ano
tbe antlbooy wlll ensure tbat tbe agent ls carrleo only to tbe target cells ano nowbere else.
Antlbooles can be maoe to target a tolc agent (e.g. a raoloactlve substance) to cancer cells ano
nowbere else ln tbe booy.
Antlbooles to tbe proteln bormone bCG, proouceo ln pregnancy, are bouno to a test strlp ano useo to
oetect tbe presence ot bCG ln urlne ln a pregnancy test strlp.
Antlbooles are useo to oetect tbe presence ot specltlc protelns ln very low concentratlons ln tbe LL|SA
assay.
Fluorescent antlbooles are useo to staln partlcular cell organelles ln mlcroscope slloes.
Antlbooles can be useo olrectly ln passlve lmmunlty to belp tbe booy's normal lmmune response to a
serlous lntectlon (see p80).


Appendix 1 ~ MathenaticaI Requirenents
8lology ls a quantltatlve sclence, ano a reasonable matbematlcal ablllty ls epecteo ln an A-level blology
eam. Tbe AQA specltlcatlon states tbat you can be testeo on any ot tbese matbematlcal toplcs:

CaIcuIations
Use stanoaro torm, ratlos, tractlons ano percentages.
Calculate F F F
+
, 1 , , mean, ano stanoaro oevlatlon.
Calculate percent cbange ano rate ot cbange.
Calculate clrcumterences ano areas ot clrcles, ano surtace areas ano volumes ot cubolos ano cyllnoers
wben provloeo wltb approprlate tormulae.
Use unlts wltb pretles (n, , m, k, M, G) ano use an approprlate number ot slgnltlcant tlgures.
Make estlmates ot tbe results ot calculatlons wltbout uslng a calculator.
Rearrange equatlons ano substltute numerlcal values lnto equatlons uslng approprlate unlts.

HandIing data
Unoerstano tbe terms mean, meolan ano mooe ano stanoaro oevlatlon.
Unoerstano tbe use ot logarltbms tor quantltles tbat range over several oroers ot magnltuoe.
Construct ano lnterpret trequency tables, bar cbarts ano blstograms.
Use a scatter olagram to loentlty posltlve ano negatlve correlatlon between two varlables.
Plot grapbs trom oata (uslng approprlate lnstltute ot blology conventlons) ano reao oata trom grapbs.
Unoerstano tbe prlnclples ot sampllng as applleo to blologlcal oata.

Some ot tbese matbematlcal requlrements are eplalneo on tbe net two pages.

5l Units
8lologlcal measurements are always maoe uslng stanoaro "S|" unlts. Tbere are tunoamental ano oerlveo
unlts. Tbe maln unlts useo ln blology are:
Quantity Unit 5ynboI Notes
lengtb metre m
mass kllogram kg
amount ot substance mole mol
tlme secono s Never use sec. Mlnutes (mln), bours (b), oays (o) ano years (y) are
also useo wben more approprlate.
temperature oegree
celclus
C Tbe kelvln (K) ls tbe S| unlt ot temperature, but ls rarely
approprlate ln blology, wbere C ls mucb more common. Never
use tbe term centlgraoe. 0C = 273.15 K.
torce newton N 1 N = 1 kgm s
-2

pressure pascal Pa 1 Pa = 1 Nm
-2

energy joule [ 1 [ = 1 Nm
volume lltre L 1 L = 10
-3
m = 1om. volume sboulo strlctly be measureo ln m,
but tbe lltre ls more usetul ln blology ano ls wloely useo. Try not
to ml tbe tlgure 1 ano tbe letter l (use L). Lams usually use cm
(= mL).
concentratlon g L
-1
or mol L
-1

speeo m s
-1

rate ot reactlon mol s
-1
or any measure ot progress / any unlt ot tlme (e.g. g mln
-1
)

All S| unlts can take tbese pretles ln tront ot tbem to make tbem smaller or larger:
10
-3
mllll m 10
3
kllo k
10
-6
mlcro 10
6
mega M
10
-9
nano n 10
9
glga G
10
-12
plco p 10
12
tera T

The Thousands RuIe. Tbe pretles lncrease or oecrease by tactors ot a tbousano, so by cbooslng tbe
rlgbt pretl, all values can be ln tbe range 1999.
e.g 10 mm lnsteao ot 0.01 m
2.56 MPa lnsteao ot 2 560 000 Pa
75 L lnsteao ot 0.075 mL.

values may also be epresseo ln stanoaro torm (or sclentltlc notatlon) e.g. 3.2 10
6
cells mL
-1
. You sboulo
be able to convert between tbese torms e.g. 4 10
-8
m = 40 nm.

Never use centl (c, 10
-2
) or oecl (o, 10
-1
), e.g. cm, om. Tbey oon't tollow tbe tbousanos rule ano so cause
contuslon.
Names ot unlts are always spelt wltb a small letter, even lt tbey're nameo atter sclentlsts (e.g. joule).
Symbols oo not neeo a tull stop (llke an abbrevlatlon) or an s (llke a plural) e.g. 3 mln not 3 mlns.
Tbere sboulo be a space between tbe value ano lts symbol (e.g. 6 g not 6g)
Tbere ls no space between a pretl ano a symbol (e.g. 7 mN not 7 m N)
Use a space to lnolcate tbousanos, not a comma (e.g. 72 000 not 72,000)
Use tbe lnoe
-1
tor olvlslon ln unlts, not a slasb (e.g. ms
-1
not m/s)
|t you oon't know alreaoy, tlno out bow to use subscrlpts ano superscrlpts ln your woro processor.

The Greek AIphabet
Greek letters are otten useo ln blology (ano otber sclences), so tor reterence, bere ls tbe 24-letter Greek
alpbabet. To get tbese on a PC, use tbe Roman equlvalent letter, ano set tbe tont to "Symbol". Mu () ls
also avallable ln any tont uslng ALT-0181.
Nane
uppercase
Ietter
Iowercase
Ietter
Ronan
equivaIent
Nane
uppercase
Ietter
Iowercase
Ietter
Ronan
equivaIent
Alpba

a Nu

n
8eta

b Xl

Gamma

g Omlcron

o
Delta

o Pl

p
Lpsllon

e Rbo

r
eta

z Slgma

s
Lta

b Tau

t
Tbeta

q Upsllon

u
|ota

l Pbl

t
Kappa

k Cbl

c
Lamboa

l Psl

y
Mu

m Omega

w

Area and VoIune
You sboulo know, ano be able to use, common tormulae sucb as:
clrcumterence ot clrcle = 2r area ot clrcle = r
2

surtace area ot cube = 6s
2
volume ot cube = s
3

You may also be glven, ano bave to use, otber tormulae sucb as:
volume ot cyllnoer = r
2
b surtace area ot cyllnoer = 2rb (+ 2r
2
tor tbe enos)
volume ot spbere = 4r
3
/3 surtace area ot spbere = 4r
2

Percentage Change
A common eam questlon ls to calculate percentage cbange. Tbe tormula ls:

100
value startlng
value) startlng - value (tlnal
cbange =

Percent cbanges can be posltlve (lncreases) or negatlve (oecrease). |t ls also posslble to bave cbanges
greater tban 100.

For eample:
lt tbe skln temperature ot an atblete cbanges trom 37.0 C to 37.5 C, tbere ls a cbange ot +1.35
lt tbe area ot a oecomposlng leat cbanges trom 150 mm to 80 mm, tbere ls a cbange ot -46.7
lt tbe leat area ot a growlng tree cbanges trom 0.6 m to 3.7 m, tbere ls a cbange ot +517


Appendix 2 ~ The Unit 1 Exan

Tbe tbree AS blology unlts are assesseo as sbown ln tbls table:
Unit Assessnent DetaiIs
Raw
narks
UM5
narks
Unit 1 1b 15mln eam
5-7 sbort answer questlons plus 2 longer questlons:
1 comprebenslon ano 1 contlnuous prose.
60 100
Unit 2 1b 45mln eam
9 sbort answer questlons plus 2 longer questlons:
1 oata banollng ano 1 HSW.
85 140
Unit 3 AS LMPA
2-3 practlcal sesslons wltb sbort wrltten task sbeets
plus a 1b 15mln eam.
50 60

8lology ls not just about learnlng tacts (tbougb tbere ls a lot to learn): lt's largely about unoerstanolng
prlnclples ano belng able to apply tbese prlnclples to untamlllar sltuatlons (wblcb ls wbat bappens ln real
llte). |t's also lmportant to unoerstano How Sclence Works, ano tbe role ot evaluatlon ano crltlcal tblnklng.
So tbe A2 blology eams test all tbese aspects. Ot tbe 60 raw marks ln tbe unlt 1 eam, about 25 wlll be
tor blologlcal knowleoge, 25 wlll be tor applylng tbat knowleoge to untamlllar sltuatlons ano analyslng oata,
ano 10 wlll be tor How Sclence Works, lncluolng plannlng, analyslng ano evaluatlng eperlments. So epect
lots ot questlons about oata analysls. Tbese are oeslgneo to test your knowleoge ot unlt 1 blology ln
untamlllar contets.

Exan Technique
40 ot all eam marks lost are lost oue to poor eam tecbnlque.
Reao tbe questlon! You wlll only get marks tor oolng eactly wbat lt asks, e.g. lt a questlon says eplaln
bow A causes 8 tben start at A ano tlnlsb at 8.
Do wbat tbe questlon says. |t lt says use tbe olagram to... or use tbe grapb to..., tben you must oo
so.
|t a questlon says glve two reasons tben glve eactly two. You wlll lose marks lt you glve tbree.
Reao tbe wbole questlon betore answerlng any ot lt. Tbls belps unoerstanolng.
Use tecbnlcal terms ln every answer. |n general a tecbnlcal term useo correctly ls wortb one mark.
Melosls causes alleles to be recomblneo ls more llkely to earn a mark tban melosls mles genes.
Look at tbe marks. Don't wrlte too mucb tor a 1-mark answer, ano oo wrlte 3 gooo tblngs tor a 3-mark
answer.

Exan 5trategy
40 ot tbe marks are almeo at L-graoe canoloates, so sboulo be talrly easy to get. You coulo try tlnolng
ano oolng tbese questlons tlrst.

|n longer answers (5 or more marks) try wrltlng your answer ln bullet polnts, wbere eacb statement ls
wortb one mark. Tbat wlll torce you to be loglcal ano put a tecbnlcal term lnto every sentence, ano lt
wlll belp tbe eamlner to tlno your polnts.

Content and 5ynopsis
|n general questlons wlll only test tbe content ot tbe specltlcatlon tor tbat unlt. However:
Some baslc loeas (llke cells, olttuslon, osmosls, protelns, enzymes, etc.) coulo crop up ln any unlt.
Knowleoge wlll otten be testeo ln untamlllar contets, so you may neeo to work out wbat part ot tbe
specltlcatlon ls actually belng testeo. Don't panlc questlons on blppopotamuses aren't really about
blppopotamuses.
Tbe essay ln Unlt 5 ls tbe only real synoptlc questlon, wben you wlll be epecteo to lntroouce loeas
trom many parts ot tbe course (more oetalls below).
How Sclence works wlll be testeo ln all unlts.

Describing and ExpIaining data
Unoerllne tbe woros oescrlbe ano eplaln on your paper, to remlno you to oo tbe rlgbt one.
|t you are askeo to oescrlbe some results (trom a table or a grapb) look tor oltterent pbases e.g. as X
lncreases Y lncreases up to 30 oays tben levels ott. Always quote a value trom tbe grapb usually tbe
X-value wbere tbe grapb cbances sbape.
|t you bave to oescrlbe a grapb wltb tluctuatlng or nolsy oata (a jaggeo llne), try orawlng a smootb llne
ot best tlt tbrougb tbe oata tlrst, ano tben oescrlbe tbat.
|t you are askeo to oescrlbe some results trom a table lt mlgbt be a gooo loea to sketcb a qulck grapb on
tbe eam paper so you can see tbe pattern more clearly.
Do not eplaln tbe results lt you are not askeo to.
|t you are askeo to eplaln some results lt's otten a gooo loea to oescrlbe tbem brletly tlrst (even lt
you're not askeo to), so you know wbat you're eplalnlng.

Maths and 5tatistics
Tbere wlll be matbs questlons! You must be contloent wltb unlts ano pretles (especlally m, ano n).
You neeo to know tbe tormulae tor magnltlcatlon, percent cbange ano graolent ot a grapb.

How 5cience Works
Tbere wlll be How Sclence works questlons ln all eams, so cbeck you know all tbe terms.
|t you are askeo to oeslgn an lnvestlgatlon, tbe marks wlll be tor talr testlng (tbougb oon't use tbls term):
bow to cbange tbe lnoepenoent varlables, bow to quantlty tbe oepenoent varlable, namlng some control
varlables, oolng repeats.
You neeo to unoerstano all tbe How Sclence Works woros on tbe net page.

*+,'- %/ 0)1)
Data
(measurements, slngular oatum)
Quantitative or
Nuneric Data
(numbers)
QuaIitative or
Categoric Data
(woros)
Continuous Data
can bave any value
e.g. 7.34, -294.6, 210
5
Discrete Data
only wbole numbers
e.g. no. ot atoms
Ordered Data
can be rankeo
e.g. small, meolum, large
NoninaI Data
can't be rankeo
e.g. male, temale
ControIIed Experinent {
Wben all relevant varlables are controlleo, so tbat observeo cbanges ln tbe
oepenoent varlable must be oue to cbanges ln tbe lnoepenoent varlable.
Fair Test}
PIacebo
A oummy plll, lnjectlon or treatment tbat bas no pbyslologlcal ettect (e.g. a sugar
plll or sallne lnjectlon). Useo ln a cllnlcal trlal to allow tor tbe -
tbe observatlon tbat symptoms can lmprove wben patlents belleve tbey are
belng belpeo.
pIacebo effect
Hypothesis
A suggesteo eplanatlon ot observatlons or results tbat can be testeo. Also
known as a sclentltlc bypotbesls. A gooo bypotbesls can be useo to make
predictions.
ProtocoI
A metboo or tecbnlque tbat bas been sbown to proouce vallo ano rellable
results.
RCT
Tbe best eperlmental oeslgn tor a orug trlal. RCT stanos
Controlleo Trlal, or ln more oetall, a Ranoomlseo, Placebo-Controlleo, Double-
bllno Trlal. Tbls oeslgn ensures tbat tbe trlal ls tree trom .
means tbe stuoy ano control groups are allocateo ranoomly
means tbe stuoy group (taklng tbe orug to be testeo) ls
compareo to a placebo group (wbo are glven a placebo).
means tbat neltber tbe subjects nor tbe lnvestlgators know
wbo ls ln tbe stuoy or placebo groups. Tbls avolos blas.
vaIid bias
Randonised
PIacebo-controIIed
DoubIe-bIind
!
!
!
tor Ranoomlseo
ControI Experinent {ControI}
An aooltlonal eperlment oeslgneo to ellmlnate alternatlve eplanatlons tor tbe
maln eperlment, ano so sbow tbat observeo cbanges ln tbe oepenoent varlable
must be oue only to cbanges ln tbe lnoepenoent varlable.
ControI Group
A group or sample treateo ln tbe same way as tbe eperlmental group, ecept
tor tbe tactor belng lnvestlgateo e.g. a placebo group ln a orugs trlal. 8y
comparlng tbe results tor two groups lt can be sbown tbat observeo cbanges ln
tbe oepenoent varlable must be oue only to cbanges ln tbe lnoepenoent varlable.
23,'(45'61)& 0'-476
5tatisticaI Test*
Sometbl ng tbat tests wbetber
observeo oltterences or correlatlons
are slgnltlcant, or just oue to cbance.
NuII Hypothesis*
Tbe statement tbat ls testeo by a
statlstlcal test. Tbe null bypotbesls ls
tleo tor eacb test, but always says tbat
tbere l s no ol tterence or no
assoclatlon. Tbe null bypotbesls bas
notblng to oo wltb a sclentltlc
bypotbesls.
8-vaIue*
Tbe result ot a stats test, epresseo as a
probablllty. |t ls tbe probablllty tbat tbe
results are oue to cbance. |t <0.05
tben we reject tbe null bypotbesls,
otberwlse we accept lt.
A
CausaI ReIation
Wben cbanges ln one varlable
tbe cbanges ln anotber varlable. Can
only be sbown by a controlleo
eperlment.
cause
CorreIation {or Association}
Wben one varlable cbanges wltb
anotber varlable, so tbere ls a relatlon
between tbem. Tbe strengtb ot a
correlatlon can be measureo uslng a
correlatlon coettlclent. A correlatlon
neeo not be a . causaI reIation
91)14-14#)& :6)&+-4-
RepIicates
Repeats ot a measurement.
Range
Tbe bl gbest ano lowest
repllcates, or tbe lnterval
between tbem.
5tandard Deviation {5D}
A measure ot tbe olspersal ot tbe repllcates
about tbe mean. |n a normal olstrlbutlon 68
ot tbe repllcates wlll be wltbln 1 stanoaro
oevlatlon ot tbe mean, ano 95 wlll be wltbln 2
stanoaro oevlatlons ot tbe mean.
5tandard Error of the nean {5EM}*
A measure ot tbe uncertalnty, or error, ot a
calculateo mean. Tbe smaller tbe stanoaro error,
tbe more rellable tbe mean.
95 Confidence lntervaI {Cl}*
Anotber measure ot tbe error ot tbe mean. We
can be 95 contloent tbat tbe true mean lles ln
tbe range (mean C|). Tbe top ano bottom ot
tbls range are calleo tbe . confidence Iinits
Raw Data
Tbe orlglnal measurements or
re cor ol ngs bet or e any
manlpulatlon or processlng.
Mean Average or
Tbe ml o- pol nt ot t be
repllcates.
= sum ot repllcates / N
945,&' :6)&+-4-
Randon Errors
|naccuracles oue to mlstakes, poor
tecbnl que, or ranoom varlatl on.
Ranoom errors are very common, but
can be lmproveo by taklng many
repllcates. Data wltb a small ranoom
error ls salo to be . precise
5ystenatic Errors
|naccurate measurements ln one
ol rectl on onl y, oue to poor
or poor tecbnlque.
Systematlc errors can be
lmproveo by taklng more repllcates.
caIibration
not
Data wltb a small systematlc error ls
salo to be reIiabIe.
Zero Error
A partlcular klno ot systematlc error,
wbere tbe lnstrument ooes not return to
zero.
Bias
Wben tbe observer cbooses some
results ano lgnores otbers, to support a
partlcular vlew. Also calleo
.
cherry
picking
CaIibration
Lnsurlng tbat a measurlng lnstrument
glves correct reaolngs by tllng known
polnts tben constructlng a scale
between tbem.
AnonaIy or OutIier
A measurement tbat talls tar outsloe
tbe epecteo range ano ls tberetore
probably oue to eperlmental error.
Anomalles sboulo be rejecteo, slnce
tbey skew tbe mean, but lt ls very
olttl cult to ol stlngulsb between
anomalles ano normal blologlcal
varlatlon.
Accurate Data
Measurement tbat are close to tbe
true vaIue.
Precise Data
1.
val ues wben repeateo. Tbe
repllcates tberetore bave a small
.
2. Data measureo on sensl tl ve
equlpment wltb a sultably tlne scale,
e.g. 20 mm ls more preclse tban 2
cm.
range
Measurements tbat glve slmllar
;<)&41+ %/ 0)1)
Anecdote
An observatlon or story trom real llte.
Anecootes are not evloence ano
cannot be useo to support a
bypotbesls, but tbey can be usetul to
suggest a new testable bypotbesls.
VaIid Data
Tbe best quallty oata, l.e. oata tbat ls
ano ano obtalneo
trom an ,
eperlment tbat aooresses tbe stateo
alm. vallo oata ls assumeo to be
accurate.
precise reIiabIe
unbiased controIIed
ReIiabIe Data
Flnolngs tbat can be repeateo. Tbls
lncluoes by tbe orlglnal lnvestlgator, by
otber sclentlsts, by otber tecbnlques,
or tbose tbat agree wltb seconoary
sources.
Evidence
Any oata or observatlons tbat
to support a partlcular bypotbesls.
are useo
True VaIue
Tbe real value ot a measurement, lt lt
coulo be measureo wltb no errors at
all.
*+,'- %/ !)(4)=&'
lnoepenoent varlable
o
e
p
e
n
o
e
n
t

v
a
r
l
a
b
l
e
Dependent VariabIe
Tbe varlable you , to see
bow lt ls attecteo by tbe
lnoepenoent varlable.
3-8&4/-
Confounding VariabIes
Any varlables tbat coulo also attect tbe
oepenoent varlable. Contounolng
varlables sboulo be
controlleo ln a talr test.
lndependent
VariabIe
Tbe varlable you
, to see bow lt
attects tbe oepenoent varlable.
You may also measure lt wben
you cbange lt.
$7%%&-
.% $78+!-
ControI variabIes
Contounolng varlables tbat
are kept constant
(controlleo) ourlng tbe
eperlment. |t you can't control a varlable
(sucb as weatber ln a tlelo lnvestlgatlon),
you sboulo at least monltor lt

Biology Unit 1 Notes

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AS 8lology Unlt 1 page 1

HGS 8lology A-level notes NCM/7/11

), wltb tour oltterent

AS 8lology Unlt 1 page 11

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