HighlightsEnzymeControlI

1.Allosterismisonlyonewayofcontrollingenzymes.ATCaseisanexcellentexampleofan
allostericallycontrolledenzyme.Itcatalyzesthefirststepinamultistepprocess.Theendproductof
thispathway/processisCTP.CTPbindstotheregulatorysubunitsforATCaseandinactivatesthe
enzyme.Bycontrast,ATPbindstothesamesubunitsandcausestheenzymetobeactivated.Activation
ofanenzymeresultsinconversionofitfromtheTtotheRstate.Inactivationofanenzymecausesthe
enzymetoconvertfromtheRtotheTstate.Aspartateisasubstratefortheenzymethatalsoactivates
itandconvertstheenzymeintotheRstate.Aspartatebindstotheenzyme'scatalyticsubunits.
2.Wehavetwomechanismsforexplainingenzymesareactivatedorinactivatedallosterically.They
arecalledthesequentialandtheconcertedmodels.
3.Thesequentialmodelsaysthatbindingofamoleculebyanenzymecausesthechangeintheenzyme
fromRtoTorfromTtoR.Thereisacauseeffectrelationshipbetweentheallostericeffector
(moleculeaffectingtheenzyme)andthestateoftheenzyme(TorR).
4.Theconcertedmodelsaysthatthereisnocauseeffectrelationbetweentheeffectorandthestateof
theenzyme.Instead,itstatesthattheenzyme"flips"fromRtoTorTtoRbyitselfandthenbindingof
aneffectorLOCKStheenzymeintothatstate.
5.Anotherpowerfulmechanismforcontrollingsomeenzymesiscovalentmodification.Covalent
modificationinvolvesmakingorbreakingcovalentbondswithinortoanenzyme.Onecommon
covalentmodificationisphosphorylation(puttingonaphosphate)ordephosporylation(takingoffa
phosphate).Onlythehydroxylatedaminosacids(serine,threonine,ortyrosine)aretypically
phosphorylated.
6.Enzymesthatputphosphatesontothingsarecalledkinases.Enzymesthattakephosphatesoffare
knownasphosphatases.
7.Averycommontypeofcovalentmodificationisphosphorylation,asexhibitedbyGlycogen
Phosphorylase.Phosporylationconvertsglycogenphosphorylaseb(lessactive)toglycogen
phosphorylasea(moreactive).Thekinasethatputsthephosphatesoniscontrolledbyepinephrine
(adrenalin).

1.Genetherapyaimstoreplacedefectivegeneswithfunctionalcopies.Partiallydisabledretroviruses
aresometimesemployedtoaccomplishthis.
2.SinceretroviruseshavealifecyclethatincludesaDNAstageandthisDNAgetsintegratedintothe
genomeofthehostorganism,theyarepotentiallyusefulforcarryinggenesintothegenometocorrect
geneticdefects.Theysufferfromthedisadvantagethatitisdifficulttotargetexactlywhereinthe
genomethattheirDNAintegrates.
3.Theimmunesystemreliesonproteinccalledantibodiesthatrecognizeandbindtospecificstructures
asfoundinproteins,nucleicacids,orcarbohydrates.AnantibodyhasaYshapecontainingfour
polypeptidechainstwolongeronescalledHeavychainsandtwoshorteronescalledLightchains.
Eachofthesechainshasaconstantregionandavariableregion.Thevariableregionisthepartthat
bindstothetarget.Thetargetiscalledanantigenandthespecificpartoftheantigenwheretheanibody
bindsiscalledtheepitope.

4.Oncogenesaregenesthatcausecancer.Theyarisefromnormalcellulargenescalledproto
oncogenesbymutation.Theprotooncogenesgenerallyhaveveryimportantrolesinhelpingtocontrol
cellulardecisionsregardingwhetherornottodivide.
5.Forsomeoncogenes,mutationofasinglebasemaydisruptcellularcontrolsfordivisionandconvert
acellfromnormaldivisiontouncontrolleddivision.

HighlightsCarbohydrates
1.Glucoseandfructosearecommoncarbohydrates(sugars)anddifferonlythatglucoseisanaldehyde,
whereasfructoseisaketone.Bothhavesixcarbonsandyoushouldknowtheirstructures(linearand
circularformsseebelow).
2.Theletters'ose'attheendofanamedesignateasugar.Analdoseisasugar,likeglucose,thatisan
aldehyde.Aketoseisasugarlikefructosethatisaketone.Ahexosehassixcarbons,apentosehasfive
carbons,atetrosehasfourcarbons,andatriosehasthreecarbons.
3.TheLformofasugar(likeLglucose)differsfromtheDformofasugarofthesamename(likeD
glucose)inthatthetwoaremirrorimagesofeachother.Sugarsthataremirrorimagesofeachotherare
calledenantiomers.Sugarmoleculesthathavethesamenumberofcarbons,andhavedifferent
stereoisomericconfigurationsbutthatareNOTmirrorimagesofeachotherarecalleddiastereomers.
Sugarsthatdifferonlyintheconfigurationofonehydroxylgrouponasinglecarbonarecalled
epimers.
4.Sugarscanformaringstructureduetothefactthatcarbons1and5(or2and5)arelocatedinclose
promitytoeachotherandthealcoholoncarbon5canreactwiththealdehydeoncarbononeorthe
ketoneoncarbontwotoformahemiacetalorhemiketalrespectively.Theresultingringstructureis
calledaHaworthprojection.Thelinearform,aswritten,iscalledaFischerprojection.
5.Sugars,likeglucose,thatformsixmemberedringsarecalledpyranoses,whereassugars,like
fructoseandribose,thatformfivememberedringsarecalledfuranoses.
6.Formationofaringcreatesanewasymmtriccarbon(calledtheanomericcarbon)onthecarbon
wherethealdehydeorketoneoriginallywas(carbon1or2).Thehydroxylonthiscarboncanexistina
Haworthprojectionpointingupwards(beta)ordownwards(alpha).Pleasenotethatlinearformsof
thesesugarsDONOThaveanomericcarbons,sincethecyclizationiswhatcreatestheasymmetry.

HighlightsCarbohydrates2
1.YoushouldknowandbeabletodrawtheFischerstraightchainformandtheHaworthformof
glucose,fructose,andribose.YoushouldalsoknowtheHaworthstructureofsucrose.
2.Aldoses,likeglucose,arereadilyoxidized.KetosesareNOTnearlyasreadilyoxidizedasaldoses.
Sugarsthatarereadilyoxidizedarecalledreducingsugars.
3.Reductionofthealdehyeorketonestructureofasugarcanleadtocompoundslikesorbitolthatare
sometimescalledsugaralcohols.
4.Replacementofthehydrogenonthehydroxylofananomericcarbonbyanyotheratomcreatesa
glycoside.Thebondisreferredtoasaglycosidicbond.Manycarbohydratescontainingmultiplesugar

unitshaveglycosidicbonds.Sucrose(glucose+fructose)hasaglycosidicbondjoiningthetwosugars,
asdoeslactose(glucose+galactose).Carbohydrateswithtwosugarsareknownasdisaccharides.
Sugarsthatarenotglycosidescanchangereadilyfromalphatobeta,butglycosidesarelockedinthe
configurationtheywereinwhenthehydrogenwasreplacedfromthehydroxylgroupoftheanomeric
carbon.
5.Aswegetolder,wetendtomakelessoftheenzymeknownaslactase.Lactasebreaksdownlactose
intoglucoseandgalactose.Iflactaseisabsentordeficient,lactosemakesitintotheintestinewhere
bacteriabreakitdownandcreatalargeamountofgasandcauseconsiderablepain.
6.Polymersofsugarscreatepolysaccharides.Amyloseisapolysaccharideofplantsthatconsistsof
glucoseunitslinkedsolelyinalpha1,4linkages.Glycogenisastoragepolysaccharrideofanimalsthat
containsglucoseunitslinkedinalpha1,4linkagesandeverytenresiduesorso,thereisa1,6branchto
anewchainofglucose.Glycogenisthereforeverybranched.Amylopectinisapolysaccharideof
plantsthatalsoisaglucosepolymerwithalpha1,4linkagesandalpha1,6branches,butthebranches
arenotnearlyasfrequentasinglycogen.Starchisamixtureofamyloseandamylopectin.
7.Celluloseisapolymerofglucose,butinsteadofhavingunitslinkedalpha1,4,cellulosehastheunits
linkedbeta1,4.Mostanimalscannotdigestcelluloseandthuscannotderiveenergyfromit.Since
celluloseisacomponentofplantcellwalls,muchenergyislostasaresult.
8.Ruminantanimals,suchascows,havebacteriaintheirrumens(specializedstomachs)thatcontain
theenzymecellulase.Cellulasecanbreakthebeta1,4bondsbetweentheglucosesincelluloseand
provideenergytocows.
9.Sugarssometimehaveaminogroupsattachedtothem.
10.Proteoglycansarecarbohydratesattachedtoproteins.Thesugarsinthecarbohydratesare
chemicallyalteredtohaveanegativechargeandthengeativechargesrepeleachotherandgive
solutionscontainingthemaslimyfeel.Theyarefoundinhyaluronan(acompoundofsynovialfluidof
ourjoints)andinmucus.

HighlightsEnergy
1.Thefreeenergyofareaction(DeltaG)istheenergythatisavailablefor(orrequiredfor)doing
thingsincells(catalyzingreactions,doingwork,etc.).Byexaminingthefreeenergychangethat
occursinareaction,onecandetermineifareactionisfavorable(goforward)ornotfavorable(go
backward).FavorablereactionshaveDeltaGvaluesthatarenegative(alsocalledexergonicreactions).
UnfavorablereactionshaveDeltaGvaluesthatarepositive(alsocalledendergonicreactions).When
theDeltaGforareactioniszero,areactionissaidtobeatequilibrium.EquilibriumdoesNOTmean
equalconcentrations.
2.ForareactionA<=>B(notethatallreactionsaretheoreticallyreversible.Iusethesymbol<=>to
indicateareversiblereaction),iftheDeltaGisnegative,theforwardreaction(A>B)isfavored.If
theDeltaGispositive,thereversereaction(B>A)isfavored.IftheDeltaGiszero,thereisnonet
changeinAandB,asthesystemisatequilibrium.
3.TheDeltaGforthereactionA<=>Bcanbecalculatedfrom
DeltaG=DeltaGzero+RTln([B]/[A]).Iwillsimplifythisforourclasstothefollowingform:
DeltaG=DeltaGzero+RTln([Products]/[Reactants])

4.Metabolicenergyarisesfrombreakdownoflargermoleculestosmallerones.Thisiscalled
catabolism.Synthesisoflargermoleculesfromsmalleronesiscalledanabolism.Catabolisminvolves
oxidationandreleasesenergy.Anabolisminvolvesreductionandrequiresenergy.

HighlightsEnergy
1.OxidationproducesenergyforcellstomakeATP.ATPisthecurrencyofthecellsandisusedin
anabolicreactionstosynthesizethings.
2.ATPhashighenergyduetothemutualrepulsionofthephosphatesitcontains.
3.NADHandFADH2mustreadilybeconvertedbacktoNAD+andFADinthecelloroxidative
reactionswillhavenoplacetotransferelectronsto.

HighlightsGlycolysis
1.Glycolysisisametabolicpathwayforthebreakdown(catabolism)ofglucoseandrelatedsugars.The
pathwayrequirestwoATPstostarttheprocessandgenerates4ATPS(foranetoftwoATPs)per
glucose.AlsogeneratedduringglycolysisaretwoNADHs.
2.ThetwoNADHsproducedinglycolysisareafactorindeterminingwhichpathwaysistakenafter
pyruvateisproducedinglycolysis.
3.Thelecturecontainsinfoneededtoknowfortheexamregardingstructures,names,andenzymes.
Hexokinase(needtoknow)isanenzymethatcatalyzesthefirststepinglycolysis.ItusesanATPto
putaphosphateontoglucose,makingglucose6phosphate(G6P)andADP.
4.G6Pisconvertedtofructose6phosphate(F6P)inthenextstepofthepathway.
5.ConversionofF6Ptofructose1,6bisphosphateiscatalyzedbytheenzymephoshofructokinase
(PFK)(needtoknow).ThisreactionalsorequiresATP.
6.Inthenextstepofglycolysis,thesixcarbonF1,6BPissplitintotwothreecarbonpieces(DHAPand
G3P)catalyzedbytheenzymealdolase(needtoknow).ThedeltaGzeroprimeforthisreactionisvery
positive,meaningthatthereisanenergybarriertogetover.
7.Thetwothreecarbonpiecesarethenconvertedintothesameformglyceraldehyde3phosphate
(G3P).
8.Reaction6ofglycolysisinvolvestheonlyoxidation.Theenzymeresponsibleisglyceraldehyde3
phosphatedehydrogenase(G3PDHneedtoknow).Inthereaction,thealdehydeofG3Pisconverted
toanacidgroup,whichissubsequentlylinkedtoaphosphate.Notethattheenergyoftheoxidation
providesthenecessaryenergytoputthephosphateon.ATPisnotrequired.
9.Inreaction7,ATPisgenerated.Sincetherearetwothreecarbonmoleculespersixcarbonglucose,
twoATPsareproducedperstartingglucose.Thisreactionisreferredtoasasubstratelevel
phosphorylation(ATPbeingmadedirectlyfromADPbytransferofaphosphatefromanother
moleculewithphosphate).Substratelevelphosphorylationisoneofthreetypesofphosphorylationin
cells.Theothertwoareoxidativephosphorylationinmitochondriaandphotophosphorylationof
photosynthesisinchloroplasts.

10.Reaction8isasimpleisomerization.Anintermediateintheprocessis2,3BPG.Reactionnine
involvesremovalofawatermoleculefromeachthreecarbonintermediatetoformthehighenergy
moleculecalledphosphoenolpyruvate(PEP).
11.Reaction10isthe"bigbang"reactionofglycolysis.ItproducesanotherATPforeachPEP(by
substratelevelphosphorylation)andinturn,eachPEPisconvertedtopyruvate,theendproductof
glycolysis.Theenzyme,pyruvatekinase,isanimportantone,asitprovidesyetanothercontrolpoint
forglycolysis.Pyruvatekinaseiscontrolledbybothallostericandcovalentmodifications.This
reactionisVERYenergeticallyfavorableandhelpsto"pull"earlierreactionsthatarenotsofavorable.
12.Glycolysisisregulatedbythreeenzymeshexokinase,phosphofructokinase,andpyruvatekinase.I
willsaymoreaboutregulationlater.

1.Animals,plants,andmicroorganismsusethesamepathwayfrompyruvatewhenoxygenisavailable.
ThisinvolvesconvertingpyrvateintoacetylCoAforoxidationinthecitricacidcycle.Whenoxygenis
present,NADHdonatesitselectronstotheelectrontransportsystem,creatingNAD+.Thismeansthere
isplentyofNAD+whenoxygenisabundant.
2.Inanimals,lactateismadefrompyruvatewhenoxygenismissing(anaerobicsuchasinmuscles
duringheavyexertion).ThisisdonetoregenerateNAD+,whichislowinlowoxygenconditions.
NAD+isneededtokeepglycolysisgoingundertheseconditions.
3.Inmicroorganisms,pyruvateisconvertedtoethanolduringanaerobicconditionsforthesame
reasonslactateismadeinanimalsbecauseitcreatesNAD+neededtokeepglycolysisgoingwhen
oxygenconcentrationislow.
4.Pyruvateistheendingpointforglycolysis.Whichpathwayistakenfromthatpointforwarddepends
ontheneedsofthecell.SincecellshaveaVERYstronginterestinkeepingglycolysisgoing,the
primaryconsiderationiskeepingNAD+levelshigh.Underaerobicconditions(plentyofoxygen),
NAD+isreadilymadefromNADHwithoutproblems.Thusunderaerobicconditions,cells(animal
andmicrobialcells)convertpyruvatetoacetylCoA,CO2,andNADH,sincetheNADHcanreadilybe
convertedbacktoNAD+.
5.Metabolismofglucosebyanaerobicpathwaysdoesnotreleasenearlyasmuchenergyaswhen
glucoseismetabolismbytheaerobicpathway.Notethatconversionofpyruvatetoethanolby
microorganismsisatwostepprocess.Thelaststepintheprocessiscatalyzedbyalcohol
dehydrogenase.Inmicroorganisms,thedirectionofthereactionistowardsproducingethanol.Animals
alsohaveanalcoholdehydrogenase,buttheyuseitforthereversedirectiontobreakdownethanol.
Theproductofthereversereactionisacetaldehydeandmayberesponsibleforhangovers.
6.Glycolysisisregulatedbythreeenzymeshexokinase(inhibitedbyG6P),phosphofructokinase
(inhibitedbyATP),andpyruvatekinase(inhibitedbyATP).
7.Hexokinase'sregulationisnotsimpleandIdon'tdiscussithere.PFK'sregulationisallostericand
involvesseveralpossiblemolecules.TheyincludeAMP(indicateslowcellularenergyandstimulates
enzymetobeactive),F2,6BP(activatesPFKstronglyinverylowconcentrations),andATP(indicates
highenergyandinhibitstheenzymesunderhighconcentrations).
8.Pyruvatekinaseisactuallyregulatedbycovalentmodification(we'lltalkaboutthatlater)and
allosterically.AllostericactivationofpyruvatekinaseoccurswitheitherF1,6BP(feedforward
activation)orAMP(indicateslowcellularenergy).AllostericinhibitionoccurswithATP.Inhibitionof
pyruvatekinaseisveryimportanttokeepgluconeogenesisgoing(synthesisofglucose)whenitis
occurring.

HighlightsCitricAcidCycle
1.Thecitricacidcycleoccursinmitochondria.Themostimportantstructuralfeatureofmitochondria
aretheinnnermembrane,thematrix(wheretheenzymesaredissolved),andthecristae(theinfoldings
oftheinnermembrane).Inthecycle,youdonotneedtoknowstructures,butyoushouldknowall
namesandenzymenames.
2.Theoxidativedecarboxylationofpyruvate(oxidative=NADHproduced),isareactionthatoccurs
AFTERglycolysisinthemitochondrion,butBEFOREtheCitricAcidCycle.Thereactioniscatalyzed
bythepyruvatedehydrogenasecomplex,toformacetylCoAANDmakesanactivatedformofacetate
athioesterbondinacetylCoA.FivecoenzymesareinvolvedTPP(thiaminepyrophosphate),NAD,
FAD,CoenzymeA,andlipoicacid.TPPcarriesthedecarboxylatedtwocarbonpiecetolipoicacid,
whichiswheretheoxidationoccurs.
3.Thecyclicpathwayofthecitricacidcycle(alsocalledTCAcycleorKreb'sCycle)isgenerally
consideredto"start"withadditionofacetylCoAtooxaloacetate(OAA)toformcitrate.Thisfirst
reactionusesenergyofthehighenergythioesterbondtoformcitrate.CoenzymeAisreleasedinthe
process.
4.Rearrangementofcitratetoisocitrateiscatalyzedbyaconitase.
5.Thefirstoxidativedecarboxylationinthecitricacidcycle(oxidative=NADHorFADH 2produced,
decarboxylation=carbondioxideproduced)occursinthethirdstep,yieldingNADHandafivecarbon
compound,alphaketoglutarate.Theenzymeisisocitratedehydrogenase.
6.Oxidativedecarboxylationofalphaketoglutaratebyalphaketoglutaratedehydrogenase
(alphaKGDH)occursinthefourthstep.Theproductofthereactionisafourcarbonmolecule,
succinylCoA.AlphaKGDHusesthesamecoenzymesandalmostexactlythesamemechanismas
pyruvatedehydrogenase.
7.Thefifthstepistheonlystepwhereatriphosphateisdirectlyproduced(substratelevel
phosphorylation).GTPisthetriphosphateproduced,andcoenzymeAisreleasedintheprocess.Thisis
catalyzedbysuccinylCoAsynthetase.
8.Theremainingstepsofthecitricacidcyclearedevotedtoregeneratingthefourcarbonoxaloacetate
molecule.Stepsixinvolvesoxidationofsuccinate(byFAD,toproduceFADH2),catalyzedby
succinatedehydrogenase.Itistheonlyenzymeofthecyclenotfoundinthemitochondrialmatrix.
Instead,itisembeddedintheinnermitochondrialmembrane.Fumarateistheproductofthisreaction.
Theoxidationreactionthatmakesfumarateisdifferentinbeingareactionwhereprotonsandelectrons
aretakenawaytomakeadoublebondandforthisreason,FADisneededinsteadofNAD.
9.AdditionofwatertothedoublebondinfumarateyieldsLmalateintheseventhreaction,catalyzed
byfumarase.Theeighthstepofthecitricacidcycleinvolvesoxidationofmalate(byNAD+toproduce
NADH)toyieldoxaloacetate.Thisreactionisthesimpleoxidationofanalcoholtoaketoneandis
catalyzedbymalatedehydrogenase.Itisunusualinbeingarareoxidationthatrequiresinputenergy.
Thisreactionis"pulled"bythenextreaction(firstreaction)inwhichoxaloacetateismadeintocitrate.
BreakingofthebondbetweenacetateandcoenzymeA(CoA)releasesenergy,whichdrivesthat
reactionforward.
10.Bothalphaketoglutarateandoxaloacetatecanreadilybeconvertedintotheaminoacidsglutamate
andaspartate,respectively.Rememberfrompreviouslythatpyruvatecanbeconvertedtoalanine,as
well.

11.Thecitricacidcycleiscalledanaplerotic,whichmeans"tofillup"becauseseveralofits
intermediatesareimportantinotheranabolicandcatabolicpathways.Alphaketoglutarate,for
example,canbeconvertedeasilytoglutamicacid(andviceversa)andoxaloacetatecanbeconverted
toglucoseorasparticacid(andviceversa).
12.ThecitricacidcycleisregulatedlargelyatthelevelofavailabilityofNAD+andFAD.Whenthese
arelowinabundance,thepathwayslowsorstopsattheplaceswhereNAD+orFADareneeded.
13.ThecitricacidcycleplaysrolesincatabolismANDanabolism.Many

aminoacidsandfattyacidscanbeconvertedintomoleculesthatget
oxidizedinthecitricacidcycle.Ontheotherhand,intermediatesinthe
citricacidcyclecanreadilybeconvertedtoaminoacidsand/orfattyacids.
14.Themostimportantintermediatesforconversionbetweenthecitricacidcycleandaminoacidsare
oxaloacetate(asparticacid)andalphaketoglutarate(glutamate).Inaddition,pyruvate(notacitricacid
cycleintermediatedirectly)canbeconvertedeasilyintoalanine.AcetylCoA,whichisaproductof
fattyacidoxidation,isusedinthecitricacidcycle.

GlyoxylateCycle
1.Theglyoxylatecycleisrelatedtothecitricacidcycleandisfoundonlyinbacteriaandplants,not
animals.Itusesthesameenzymesasthecitricacidcycleexceptithastwoadditionalones.These
includeisocitratelyase(cleavesisocitratetoyieldglyoxylateandsuccinate)andmalatesynthase
(combinesacetylCoAwithglyoxylatetomakemalate).Afterthesuccinateandmalateareboth
convertedtooxaloacetate,therearetwooxaloacetatesattheendofthecycle,insteadofoneinthe
citricacidcycle.
2.Thus,theglyoxylatecyclecanproduceoxaloacetateforgluconeogenesisfromacetylCoA,butthe
citricacidcyclecan't.Asaresult,bacteriaandplantscanmakeglucosefromacetylCoAinnet
amounts,butanimalscan't.

HighlightsElectronTransport/Oxidative
Phosphorylation
1.Electrontransport(ETS)occursintheinnermembraneofthemitochondrion.
2.InETS,electronsfromNADHmovetocomplexIandfromFADH2,theymoveintocomplexII.
LosingelectronslikethisconvertsthemtoNAD+andFAD.
3.Electronsmovethroughthecomplexesasfollows
ComplexICoenzymeQComplexIIICytochromeCComplexIVOxygen.Whenoxygengains
electrons,itcreateswater.
4.ElectronsfromcomplexIIarepassedtoCoenzymeIIandthentheytakethesamepathway.
5.AselectronsflowthroughcomplexesI,III,andIV,protonsare"pumped"outofthemitochondrion.
This'charges'thebattery.

6.NotethatelectronsstartingwithNADHpumpmoreprotonsthatelectronsstartingwithComplexQ.
Thisultimately(inoxidativephosphorylation)resultsinproductionofmoreATPsperNADHthanper
FADH2.
7.CoenzymeQactsasa"trafficcop",acceptingelectronsinpairsandpassingthemonindividually.
8.AselectronsflowthroughcomplexesI,III,andIV,protonsare"pumped"outofthemitochondrion.
9.NotethatelectronsstartingwithNADHpumpmoreprotonsthatelectronsstartingwithComplexII.
Thisultimately(inoxidativephosphorylation)resultsinproductionofmoreATPsperNADHthanper
FADH2.
10.OxidativephosphorylationoccurswhenprotonsmoveBACKintothemitochondrion(afterbeing
pumpedout)throughacomplexcommonlycalledComplexV.ComplexVhasthemushroomlike
shape,asshowninclass.ThiscomplexROTATEsasprotonspassthroughit.Rotationofthecomplex
createsATP.
11.ComplexVhasthreesetsofsubunitsintheF1domainthatmaketheATP.Theydothisbyflipping
betweenstateslabeledL,T,andO.Flippingiscontrolledbythe'rotor'describedinclassthatis
attachedtotherotatingF0subunit.Rotationiscausedbymovementofprotonsthroughthecomplex.L
isthestatethatbindsADPandPi.TisthestatethatcompressesthemtogethertomakeATP.Oisthe
statethatreleasestheATP.
12.NotethatmakingATPrequiresADP.IfthereisnoADP,ATPSynthaseCANNOTrotateandNO
PROTONSCANPASSTHROUGH,sincetheinnermitochondrialmembraneisimpermeableto
protonsunlessithasbeenaltered.Asaconsequence,electrontransportwillstopwhenoxidative
phosphorylationisstoppedasdescribed.Thisisanimportantaspectofmetaboliccontrol.Inmetabolic
control,theinnermitochondrialmembranemustremainimpermeabletoprotons.Whenthisoccurs,the
electrontransportwon'trununlessoxidativephosphorylationisoccurringandoxidative
phosphorylationwon'toccurunlessthereisaprotongradient.Whenelectrontransportisnotrunning,
oxygenconsumptiondecreases.Whenitisrunning,oxygenconsumptionincreases.
13.Atrest,yourbody'sstoresofATParehighandADParelow.Undertheseconditions,oxidative
phosphorylationisnotoccurringmuch,sotheprotongradientremainshigh,thusstoppingelectron
transport.Whenelectrontransportstops,NADHaccumumlates,stoppingthecitricacidcycle.
14.Whenyouexercise,yourATPlevelsfallandADPlevelsrise.Thus,oxidativephosphorylation
startsandtheprotongradientfalls.Thisstartselectrontransport,whichcausesNADandFAD
concentrationstorise,thusstartingthecitricacidcycle.
15.Acompoundcalled2,4DNP(2,4dinitrophenol)wasusedasa"miracle"dietdrugaboutacentury
agowithdisastrousconsequences.Itactedtopokeaholeinthemitochondrialinnermembrane,
allowingprotonstoleakbackintothematrixwithoutpassingthroughcomplexV.Asaresult,when2,4
DNPispresent,electronsmovethroughtheelectrontransportsystem,butNOATPismade.
Consequently,cellsburneverythingtheycantotrytomakeATP,buttheycan't.Oxygenconsumption
goeswayupandthebodytemperaturegoeswayup,butnoATPismadebyoxidativephosphorylation.
Deathwasafrequentresultof2,4DNPuse.
16.Uncouplingofmitochondriaoccurswhenanythingpermeabilizestheinnerwallofthe
mitochondriontoprotons.Thenthelinkagebetweenelectrontransportandoxidativephosphorylation
isbroken.Theoppositeofuncouplingistightcoupling.
17.Electrontransportinhibitorsblockmovementofelectronsthroughthecomplexes.Onesdescribed
inclass(andthecomplexestheyblock)includerotenone(ComplexI),Amytal(I),AntimycinA(III),
Azide(IV),CarbonMonoxide(IV),andCyanide(IV).

18.Youshouldbeabletopredictwhathappensatthemolecular/metaboliclevelinvariousmetabolic
scenariosinvolvingrespiratory/metaboliccontrolsuchasIdescribedinclass.

1.ShuttlesarenecessarytocarryelectronsfromNADHintothemitochondrion.Theyincludethe
glycerolphosphateshuttleofinsectmuscle(reducesDHAPtoglycerolphosphate,whichmovesacross
innermitochondrialmembrane)andthemalate/aspartateshuttleofourcells.
2.TheglycerolphosphateshuttletakeselectronsfromNADHinthecytoplasm,butputselectronsonto
FADinthemitochondrion,resultinginfewerprotonsbeingpumped.
3.Themalate/aspartateshuttletakeselectronsfromNADH(ontooxaloacetatetomakemalate,which
istransported)andthenreversesthereactioninthemitochondrion,resultinginnoreductionofprotons
pumped.

HighlightsGluconeogenesis
1.Gluconeogenesisisthepathwaythatisinvolvedinthesynthesisofglucose.Itoperatesmostlyinthe
liverandkidney.Ituses7ofthesameenzymesasglycolysisbyrunningthereactionsintheopposite
directionfromglycolysis.Theotherthreeenzymesarereplacedbyfournewenzymesin
gluconeogenesis.Thetwoofthesearepyruvatecarboxylaseandphosphoenolpyruvatecarboxykinase
(PEPCK).
2.Pyruvatecarboxylaseisabiotincontainingenzymethatisfoundinthemitochondrionandit
catalyzestheadditionofacarboxylgrouptopyruvatetomakeoxaloacetate.ThereactionrequiresATP
3.Inthecytoplasm,PEPCKcatalyzestheconversionofoxaloacetatetoPEPandthereactionrequires
GTP.ThenextreactionsforgluconeogenesisarethereversalofreactionsofglycolysisuptoPFK.
4.ThePFKenzymaticreactionofglycolysisisreplacedbytheenzymefructose1,6bisphosphatase
(F1,6BPase).ItactstoremoveaphosphatefromF1,6BP,yieldingF6P.Thisreactionisenergetically
favorable,sinceATPisNOTregenerated(asitwouldbeiftheglycolysisreactionwerereversed).
5.Thehexokinasereactionofglycolysisisreplacedbytheenzymeglucose6phosphatase(G6Pase),
whichactstoremoveaphosphatefromG6Ptoyieldfreeglucose.Thisreactionisenergetically
favorable,sinceATPisNOTregenerated(asitwouldbeiftheglycolysisreactionwerereversed).
6.Reciprocalregulationofglycolysisandgluconeogenesisisaccomplishedmainlybythemolecule
fructose2,6bisphosphate(F2,6BP).ItactstostimulateglycolysisbyturningonPFK(yourbookcalls
itPFK1)whileatthesametimeactingtoinhibitgluconeogenesisbyturningoffthecorresponding
enzyme,F1,6BPase.Thus,whenF2,6BPispresent,glycolysisisrunningandgluconeogenesisis
inhibited.WhenF2,6BPisabsent,gluconeogenesisisrunningandglycolysisisinhibited.
CoriCycle
1.TheCoriCycleisametaboliccycleinanimalbodiesthatallowsmusclestoexportlactatetothe
bloodstream.Fromthereitgoestotheliver,wheregluconeogenesisactstoconvertthelactatebackto
glucose.Glucoseisdumpedbackintothebloodwhereitarrivesinthemusclesandisusedtocontinue
theproductionofATPinanaerobicglycolysis.Rememberthatunderstrenuoussituations,oxygenis
limiting,solactateisproducedinitiallyinthemusclesduetolackofoxygen.OxygenisNOTlimiting
intheliver,however,soitcanconvertNADHbacktoNAD+andalsosynthesizeglucose.

2.Pyruvatekinaseistheonlyenzymeofglycolysisthatisregulatedbybothphosphorylationand
allostericmeans.Phosphorylationmakesitlessactive,whereasdephosphorylationmakesitmore
active.Allosterically,ATPandalanineinhibititandF1,6BPactivatesit(byfeedforwardactivation).
3.Thepentosephosphatepathwayisthecell'sprimarysourceofNADPH,ribose5phosphate(for
nucleotidebiosynthesis),anditisawayforcellstointerchangesugarsforuseinpathways,suchas
glycolysisandgluconeogenesis.
4.Fermentationoccurswhencellsrunoutofoxygen.Oxidationofglucoseintheabsenceofoxygenis
about1/19thasefficientasitisinthepresenceofoxygen.Fermentationoccursinallcellsto
regenerateNAD+.Animalcellsconvertpyruvatetolactateandbacteria/yeastconvertpyruvateto
ethanol.

GlycogenMetabolism
1.Breakdownofglycogen(apolysaccharidecontainingmultipleunitsofglucose)iscatalyzedbythe
enzymeglycogenphosphorylase(notethattherearefourformsseebelow).Inthereactioncalleda
phosphorolysis,phosphateisusedtobreakoneglucoseunitfromglycogen,formingaglycogen
shortenedbyoneunitandamoleculeofglucose1phosphate(G1P).Theadvantageofphosphorolysis
isthataphosphateisattachedtoglucosewithoutrequiringATP.G1PcanreadilybeconvertedtoG6P
byphosphoglucomutase(andviceversatoo)andusedinglycolysis.Thus,G1Pfromglycogencanbe
usedtogeneratecellularenergyVERYfast.
2.Glycogenphosphorylaseworksfromtheendsofaglycogenmoleculeinwards.Themoreends,the
moreG1Pthatcanbereleasedrapidly.Theenzymedoesnotworkwellclosetothe1,6branchesof
glycogen,soanotherenzyme(calledDebranchingEnzyme)isusedtomoveglucosesfromabranchto
alinearchain(inanalpha1,4orientation)andmakethemavailabletothephosphorylase.Debranching
movesallbutoneoftheglucosesonthesidechain.Thelastone,whichisina1,6configuration,is
cleavedbytheenzymeinahydrolysisreaction.Theproductisfreeglucoseandistheonlyfreeglucose
producedfromglycogen.
3.Glycogensynthesisisnotexactlythesameasthereversalofglycogenbreakdown.Energyis
requiredandthisenergyultimatelycomesfromUTP.Inthisreaction,glucoseis"activated"bybeing
attachedtoUDPtoformUDPglucose(UDPG).UDPglucoseisahighenergycompound.Theenergy
betweentheglucoseandUDPisusedtodrivethereactioninpoint#6below.
4.Glycogensynthasecatalyzestheadditionofaglucosetotheendofaglycogenmoleculefroma
UDPglucose.Branchingenzymecreatesthealpha1,6linkagesofglycogen.
5.Breakdownandsynthesisofglycogenarecontrolledinoppositeways.Whenglucoseisneeded
quicklyinanemergency,thehormoneepinephrine(adrenalin)isreleasedintothebloodstream.Itbinds
tocellsandstimulatesthephosphorylationofenzymes(includingglycogenphosphorylaseand
glycogensynthase).Phosphorylationhasoppositeeffectsonthesetwoenzymes.Glycogen
phosphorylaseisactivatedbyphosphorylation,butglycogensynthaseisinhbitedbyphosphorylation.
Thus,releaseofadrenalinstimulatesbreakdownofglycogen(toreleaseglucoseforenergy)and
inhibitsthesynthesisofglycogen.
6.Theoppositeeffectofadrenalinisaccomplishedbythehormoneinsulin.Insulinisreleasedbythe
pancreaswhenbloodglucoselevelsrise.Insulinstimulatestwothings.First,itstimulatescellstotake
upglucosefromthebloodstream,reducingbloodglucoselevelstonormal.Second,insulinstimulates
thedephosphorylationofenzymes.Dephosphorylationreversesthepreviouseffectsonglycogen
phosphorylaseandglycogensynthase.Thus,dephosphorylationinactivatesglycogenphosphorylase
(convertsittothebform)andactivatesglycogensynthase(favorssynthesisofglycogen,usingallof
theglucosenewlyarrivedinthecell).

7.Thehormonesystemworkswithinseconds,butsinceitmusttravelthroughthebloodstream,itisnot
asrapidastheresponsethatcanbeobtainedallosterically.Thisisimportantinmusclecellswhenthey
mustVERYquicklyact.ATPlevelscanfallveryrapidlyandthecellsveryquicklywanttoturnon
glycogenbreakdown.Allostericcontrolsworkonboththephosphorylatedanddephosphorylatedforms
oftheenzyme.
8.Forthedephosphorylatedenzyme,AMPconvertsitfromtheTformintotheAformandeitherATP
orG6PconverttheRformintotheTform.AMPindicateslowenergy,sotheenyzmeisACTIVATED
thenandglycogenisbrokendowntoreleaseG1P,whichcanbeconvertedtoG6Pandenterglycolysis.
Forthephosphorylatedformoftheenzyme,glucosecanconverttheenzymefromtheRtotheTstate
(shuttingitdown),butifglucoseisnotpresent,theenzymewillflipautomaticallyintotheRstate.This
iswhyweconsiderthephosphorylatedformoftheenzymemoreactiveitismuchmoreeasily
activatedtotheRstate.

LipidMetabolism
1.Fatsstoreconsiderablymoreenergypergramthancarbohydrates,duetothefactthatfatsarenot
watersolubleanddonotabsorbwater.Theyarealsomore"reduced"thancarbohydratesandcanbe
furtheroxidized.
2.Fattyacidsarereleasedfromfatsorglycerosophospholipidsbylipasesorphospholipases,
respectively.Fatsarebrokendownasaresultofacascadeofreactionsstartingwithbindingofa
hormonetoareceptoronthesurfaceoftheadipocyte(fatcell).Thisstartsasignalingprocess,which
putsaphosphateontotriacylglycerollipase,activatingit,andcausingthefattobecleavedtofatty
acidsandglycerol.
3.Fattyacidsare"activated"bybeingjoinedtoCoenzymeA(CoA)inthecytoplasm.(Notethatfatty
acidsarecarriedinthebloodstreambyserumalbumin.)Totransportfattyacidsacrossthecell's
mitochondrialmembrane,however,theCoAisreplacedbycarnitine.Aftertheacylcarnitinemakesit
acrossthemitochondrialmembrane,thecarnitineisquicklyreplacedonceagainbyCoAinsidethe
mitochondrialmatrix.
4.Fattyacidoxidationoccursinsidethemitochondrion.Theprocessisreferredtoasbetaoxidation
becausethebetacarbonofthefattyacidistheonethatgetsoxidized.Onecycleofbetaoxidation
cleavesonetwocarbonunit(acetylCoA)fromthefattyacidandleavesthefattyacidshorterbytwo
carbons.Thiolaseisanenzymethatcleavestheacetylgroupfromthefattyacidchaininthelaststepof
betaoxidation.Thefirstenzymeoffattyacidoxidation,AcylCoAdehydrogenase,hasbeenlinkedto
suddeninfantdeathsyndrome.
5.Ineachcycleofbetaoxidation,oneNADHandoneFADH2isproduced.TheacetylCoAthatis
releasedcanbeoxidizedfurtherinthecitricacidcycle.
6.Oxidationofunsaturatedfattyacidsrequirestwoadditionalenzymesbeyondthoseofbetaoxidation.
ThetwoenzymesareenoylCoAisomeraseandanotherenzymeyouarenotresponsiblefor.Thefirst
enzymecatalyzesconversionofcisbondsbetweencarbons3and4totransbondsbetweencarbons2
and3soitcanbeoxidizedinbetaoxidation.Thesecondenzymecatalyzesconversionoftwodouble
bondsintoonecisdoublebondbetweencarbons3and4,whichis,inturn,convertedtoatrans
betweencarbons2and3foroxidationinbetaoxidation.

7.Ketonebodiesarethebody'smeanstoprovideenergytothebrainwhenglucoseconcentrationsare
VERYlow.Thiscanoccurduringstarvationorwithsometypesofdiabetes.Ketonebodiesaremade
byputtingtogetheracetylCoAstomakefourcarbonintermediatesbyreversingthereactioncatalyzed
bythiolase.Thefourcarbonmoleculesareconvertedtoasixcarbonmolecule(calledHMGCoA)and
itisbrokenbackdowntoafourcarbonmoleculeandacetylCoA.Ketonebodiesarecarriedinthe
bloodtothebrain.Oneoftheseintermediatesischemicallyunstableandbreaksdowntoacetone,
whichisexhaledfromthelungs.Thus,thesmellofacetoneonaperson'sbreathmaybeasignofa
seriousproblem.
8.Unsaturatedfattyacidsproducedbiologicallyarealmostalwaysinthecisconfiguration.Bycontrast,
partialhydrogenationofvegetableoils(toraisethemeltingpoint)causestransbondtobeproduced
andthustransfatsaremade.Transfatsarelinkedtoatherosclerosis.Thereasonisnotcompletely
clear,buttherandompositioningofthetransbondsmaybeafactor.

HighlightsLipidMetabolismII

1.Fattyacidsaresynthesizedinthecytoplasmandeachstepincreasesthesizeofthefattyacidbytwo
carbons.Acetylgroupsareshuttledoutofthemitochondriausingcitrate.Thus,mostfattyacidshave
evennumbersofcarbons.ManyofthestepsoffattyacidsynthesisareCHEMICALLYsimilartothe
reversalofbetaoxidation.
2.FattyacidsintheprocessofbeingsynthesizedareattachedtoamoleculecalledACP(acylcarrier
protein)insteadofCoA.Fattyacidbiosynthesisbeginswithformationofathreecarbonmolecule
calledmalonyCoA.Thiscomesaboutfromadditionofacarboxylgroup(biotinisarequired
coenzyme).TheenzymeresponsibleforthisreactionisacetylCoAcarboxylase(notethatthisenzyme
isDIFFERENTfromfattyacidsynthasebelow).AcetylCoAcarboxylaseistheonlyregulatedenzyme
infattyacidbiosynthesisandisactivatedbycitrateandinhibitedbypalmitate.MalonylCoAisreadily
convertedtomalonylACP.
3.Inthenextstepoffattyacidbiosynthesis,twocarbonsofthemalonylACParejoinedtothegrowing
fattyacidandthecarboxylgroupthatwasaddedislostascarbondioxide.
4.Theremainingstepsarethechemicalreversalofthestepsoccurringinoxidation.Sequentiallyare
reductionoftheketone,dehydrationtocreateadoublebond,andreductionofthedoublebondusing
electronsandprotonsfromNADPH.
5.Theenzymeresponsibleforfattyacidsynthesishasmultiplecatalyticactivitiesandisknownas
FattyAcidSynthase.Itcontainsallofthecatalyticactivitiesnecessarytomakefattyacidsupto16
carbonsinsize.Synthesisoflongerfattyacidsrequiresotherenzymesandoccursintheendoplasmic
reticulum.
6.1.Fatsaresynthesizedbyputtingfattyacidsontoglycerol3phosphate.Inthereactions,fattyacids
arefirstesterifiedontocarbons1and2oftheglycerol.Thiscreatesthemoleculecalledphosphatidic
acid,whichisabranchpointbetweensynthesisoffatsandglycerophospholipids.
7.Inthedirectionoffatsynthesis,thephosphateofphosphatidicacidisremovedandreplacedwitha
fattyacid,makingafat.Inthedirectionofglycerophospholipidsynthesis,thephosphateisreplacedby
thenucleotideCDP,creatingCDPdiacylglycerol(anactivatedformofdiacylglycerol).TheCDPcan
bereadilyremovedandreplacedbyothermolecules,creatingphosphatides(suchasphosphatidyl
serine,etc.).
8.SphingolipidsaremadestartingwithapalmitoylCoAandserine.Theultimateproductofthis
reactionisthemoleculecalledsphingosine,thatwehavediscussedbefore.

9.AcetylCoAisthestartingpointforsynthesisofcholesterol.Thepathwayoverlapswiththatof
ketonebodysynthesisatfirst,astwoacetylCoAsarejoinedtoformacetoacetylCoA,afourcarbon
molecule.Additionofanother2carbonsfromathirdacetylCoAcreatesHMGCoA,asixcarbon
molecule.ThenextreactioninthesynthesispathwaytocholesteroliscatalyzedbyHMGCoA
reductase.Thisenzymeisthemajorregulatoryenzymecontrollingsynthesisofcholesterolinthebody.
HMGCoAreductaseisfeedbackinhibitedbycholesterol,theendproductofthepathway.HMGCoA
reductaseisalsothetargetofcholesterolloweringdrugscalledthestatins,whichresembleHMGCoA.
10.Frommevalonate,thefollowingmoledulesareformedisoprenes(5carbonmolecules),geranyl
pyrophosphate(containstwoisoprenes),farnesylpyrophosphate(containsthreeisoprenes),squalene
(containstwofarnesylpyrophosphates,lanosterol(rearrangedformofcholesterol),and(after19steps),
cholesterol.
11.SphingolipidsarisefromjoiningofserineandpalmitoylCoA.

HighlightsLipidMetabolismIII
1.Cholesterolgivesrisetothebileacidsdetergentlikemoleculessuchascholateorglycocholatethat
helptoemulsifyfatinthedigestivesystem.Theyalsoareprecursorsofthesteroidhormones.
2.Pregnenoloneisderivedfromcholesterolandistheprecursorofallofthesteroidhormones.These
includetheglucocorticoids,suchascortisone,themineralocorticoids,suchasaldosterone,the
androgens,suchastestosterone,andtheestrogens,suchasestragen/estradiol.Amongthesex
hormones,themalehormones(androgens)areprecursorsofthefemalehormones(estrogens).The
enzymethatcatalyzesthisconversionisknownasanaromatase.Sincesometumorsarestimulatedby
estrogen,strategiesfortreatingtheminvolvetheuseofaromataseinhibitorstoceasetheproductionof
estrogens.
3.Movementoflipidsinthebodyoccursvialipoproteincomplexes(containlipidsandprotein)inthe
bloodstream.Thesestartbeingcarriedoutofthedigestivesysteminlargemoleculescalled
chylomicrons.Chylomicronsenterthebloodstreamfromthelymphsystem.Inthebloodstream,
chylomicronsmovetothecapillaries,wheretheyaredigestedbycellularlipaseenzymes.Theresultof
thisactionistoreducethechylomicronsize,creatingchylomicronremnants.Theseexitthecapllaries
andmovetotheliver.
4.Theliverservesasthemajororganregulatingtheformationandreleaseoflipoproteincomplexes
(VLDLs,IDLs,LDLs).Theliveraccomplishesthisbymonitoringtheconcentrationofcomplexes.As
theconcentrationincreases(indicatingreduceduptakebytargetcells),theliverslowsthereleaseof
complexes.Astheconcentrationdecreases(indicatingincreaseduptake),theliverreleasesmore
VLDLs.PeoplewithdeficienciesintheLDLreceptorproteinonthelivercellstendtohavehigh
concentrationsofLDLs.Theyhaveageneticdiseaseknownasfamilialhypercholsterolemia.
5.LDLsarealsocalled"badcholesterol"becauseincreasedlevelsofthemarecorrelatedwith
increasedriskofatherosclerosis(pluggedarteries)andheartattack.HDLs,bycontrast,arecalled
"goodcholesterol"becausetheyhelpinscavengingcholesterolandLDLsfromthebloodstream.
6.LDLsarealsocalled"badcholesterol"becauseincreasedlevelsofthemarecorrelatedwith
increasedriskofatherosclerosis(pluggedarteries)andheartattack.HDLs,bycontrast,arecalled
"goodcholesterol"becausetheyhelpinscavengingcholesterolandLDLsfromthebloodstream.

HighlightsPhotosynthesis

1.Photosynthesisisaprocessinplantsandsomebacteriathatuseenergyfromthelightofthesunto
synthesizeglucoseusingcarbondioxideandwaterasstartingreagents.Itaccomplishesthisina
multistepprocessthatisdividedintotwophases,calledthelightreactions(requirelight)andthedark
reactions(don'trequirelight).
2.Photosynthesisoccursinplantsinorganellescalledchloroplasts.Thethylakoiddisksofthe
chloroplastarethesiteswherethelightreactionsofphotosynthesisandthestromaisthelocationofthe
darkreactions.

AminoAcidHighlights
1.Aminoacidsarethebuildingblocksofproteins.Theyallcontainanalphacarboxylgroupandan
alphaaminogroup.Thecarbonattachedtothealphacarboxylandthealphaaminogroupisknownas
thealphacarbon.
2.Allaminoacidsexceptglycinehavefourdifferentgroupsattachedtothealphacarbon.Asaresult,
allaminoacidshaveatleastoneasymmetriccenter(thealphacarbon).Wecallacompoundwithsuch
anarrangement'chiral.'Thetwochiralformsofaminoacidsarecalled'D'and'L'.Ifoneusesordinary
chemistrytomakeaminoacids,mixturesofDandLarealwaysproduced.However,cellsuseenzymes
tomakeaminoacidsandthoseenzymesalwaysgivethesameconfigurationL.
3.Glycineistheonlyaminoacidwithnoasymmetric(chiral)carbonbecauseithastwohydrogens
attachedtoalphacarbon.
4.OnlyLaminoacidsarefoundinproteinsformedbiologically.WecanthinkofDandLforms
similartoleftandrighthands.Indeed,sometimesthetwopossibleformsarereferredtoas
'handedness'.DandLalaninearemirrorimagesofeachother.Simpleaminoacidswithonlyone
asymmetriccenterwillalwayshaveDandLformsasmirrorimagesofeachother.
5.Twentyaminoacidsarecommonlyfoundinproteins.Thepropertiesoftheaminoacidsare
determinedbythecompositionoftheRgroupsoneachofthem.
6.Aminoacidswithnonpolarsidechainscanbeamphipathic(amphiphilic)becausepartofthemis
hydrophobic(waterhating)andpartishydrophilic(waterliking).
7.AminoacidsaregroupedaccordingtothepropertiesoftheirRgroups.Youareresponsiblefor
knowingthenamesofthe20aminoacids,thegroupstheybelongtoasshowninclassandthe
compositionofanygroupswithionizingsidechains.Forexample,socalledacidicaminoacidshave
carboxylgroups(COOH/COO)intheirsidechain.Theseincludeglutamicacidandasparticacid.Loss
ofaprotonfromthesidechaincausesthesidechaintobechargednegatively.Gainoftheproton
causesthesidechaintohavenocharge.
8.Aminoacidswithaminecontainingsidechains(arginine,lysine,histidine)havegroupsthatvaryin
chargefrom+1(protonon)to0(protonoff).Lossofaprotonfromthesidechaincausesthesidechain
tohavenocharge.Gainoftheprotoncausesthesidechaintohaveapositivecharge.
9.ProlineisanaminoacidwitharingstructureaspastofitssidechainANDits.Itistheonlyamino
acidwithanalphaaminogroupthatisnotaprimaryamine(itisasecondaryamine).
10.Cysteineistheonlyaminoacidwithasulfhydrylgroup.Methioninealsocontainssulfure,butnot
intheformofasulfhydrylgroup.

11.AminoacidswithacidsidechainshaveRgroupsthat1)canlose/gainaprotonand2)are
negativelychargeduponlosingtheproton(andneutralwhentheyhavetheproton).Twoexamplesyou
shouldknowareasparticacidandglutamicacid,bothofwhichhavecarboxylgroupsintheRgroup.
12.Someaminoacidsaremodifiedaftertheyareincorporatedintoproteins.Thebestexamplesare
hydroxylysineandhydroxyproline.Bothofthesearefoundintheproteincalledcollagen.Thyroxineis
amodifiedformoftyrosinefoundinthethyroidgland.
13.Becauseaminogroupsandcarboxylgroupscangainorloseprotons,aminoacidscanhavea
varietyofcharges.
14.ThepIofamoleculeisthepHatwhichitschargeisexactlyequal.Amoleculewithanetchargeof
zeroisknownasazwitterion.
15.Peptidebondsarethecovalentbondsthatjointogetherindividualaminoacidswithinaprotein.
Theyareformedinareactionintheribosomeinwhichthecarboxylgroupofoneaminoacidisjoined
totheaminoendofanotheraminoacid.Proteinsalwayshaveafreealphaaminoendandafreealpha
carboxylend.
16.Calculatingthechargeonapolypeptideissimple.Onesimplytalliesthechargeofthealpha
carboxylgroup,thealphaaminogroup,andalloftheRgroups.Notethattheinternalcarboxyl/amino
groupsaredestroyedinmakingthepeptidebond.

HighlightsNitrogenMetabolism
1.Reductionofnitrogentoaformusefulfororganisms(callednitrogenfixation)isadifficultand
energeticallycostlyprocess.Nitrogenfixationismadepossiblebybacteriathathaveanenzymeknown
asthenitrogenasecomplex.
2.Innitrogenfixation,N2isreducedtoammoniumion(NH4+).Theprocesstheoreticallyrequiressix
electronsand12ATPstomaketwoammoniamolecules(NH3),buthydrogengasisalwaysproduced,
sotwoadditionalelectronsand4ATPsarealsoneeded(givingatotalof8electronsand16ATPs).
3.Oncereducedtoammoniumion,nitrogencanreadilybeincorporatedintotheaminoacids
glutamate,andglutamine.
4.Aminoacidsaregroupedintofamiliescorrespondingtotheprecursorstheyaremadefrom.You
shouldknowtheaminoacidsthataresimpletransaminationproductsglutamate(madefromalpha
ketoglutarate),glutamine(madefromglutamate),aspartate(madefromoxaloacetate),alanine(made
frompyruvate),asparagine(madefromaspartate).Youshouldalsoknowthefamilies/categoriesof
aminoacidanabolismglutamate,aspartate,serine,pyruvate,aromatic,andhistidine
5.Transaminationreactionsarecatalyzedbyenzymesthatusepyridoxalphosphateasacoenzyme.As
aclass,theyarecalled'transaminases.'Theyarealsocalledaminotransferases.Notethat
transaminationreactionsrequireanaminedonorandanaminerecipient(equivalentto
reduction/oxidationreactionsthatrequireelectrondonorsandrecipients).
6.Folatesaremoleculesthatcandonatesinglecarbonstometabolicprocesses.Humansrequirefolates
intheirdietanddonotsynthesizethemfromscratch.Bacteria,ontheotherhand,makethemfrom
scratch.Anintermediatetheyuseinthisregardisparaaminobenzoicacid(PABA).Folatesexistin
twomainformsforourpurposesdihydrofolatesandtetrahydrofolates.
7.AnothermoleculeinvolvedinsinglecarbontransfersisSadenosylmethionine,alsocalledSAM.
AfterSAMhasdonatedamethylgroup,itisreferredtoasSadenosylhomocysteine(SAH).

8.Anticancerdrugsandantibioticssometimestargetfolates.Bacterialcellsstartsynthesisoffolates
withparaaminobenzoicacidanddrugsthatmimicthisarethesulfadrugs.Humansgetfolateintheir
diet,sowearenotsusceptibletoactionofthesedrugs.Methotrexateisananticancerdrugthatmimics
folate.
9.Essentialaminoacidsforanorganismarethoseaminoacidsthattheorganismcannotsynthesize
themselvesandmustbeintheirdiet.Humanshave10aminoacidsconsideredessential.
10.ThecitricacidcycleintermediatesincludingacetylCoAareallintimatelyinvolvedinboth
anabolismandcatabolismofaminoacids.
11.Breakdownofaminoacids(catabolism)isdividedintothoseaminoacidswhosecarbonbackbone
formsintermediatesinketonebodyformation(acetoacetylCoAandacetylCoA=ketogenicNote
inclass,Iincorrectlycalledketogenicacidsasthosegoingthroughthecitricacidcycle.Thoughacetyl
CoAcangothroughthecitricacidcycle,goingthroughthecycleisnotthedefinitionofketogenic.The
correctdefinitionisabove),orglucosemetabolism(oxaloacetateorpyruvate=glucogenic),orboth.

NitrogenMetabolismII
1.Uricacidandureaareexcretoryformsofnitrogen.Humanprimarilyexcreteurea,whereasbirds
(anddalmations)excreteuricacid.Uricacid,whichisabreakdownproductofguanine,isNOTvery
solubleinwaterandcanformcrystals,causingthediseaseknownasgout.
2.TheUreaCycleisinvolvedinnitrogenmetabolismincells.Notehowanaminegroupofaspartateis
transferredtoformurea.YouarenotresponsiblefortheindividualreactionsoftheUreaCycle,but
shouldbeawareofthemoleculesofthepathwaythatareaminoacidsorcitricacidcycleintermediates,
aswellasthepathway'sinvolvementinmakingureabysplittingitoffofarginine.Notealsothatthe
cycleoccurspartlyinthemitochondriaandpartlyinthecytoplasm.
3.Nucleotidebiosynthesisisrelatedtonitrogenmetabolismandarisesfromverysimplestarting
compounds.Twoofthenitrogensofpurinescomefromtheamineofglutamine,onecomesfrom
incorporationofglycine,andonefromaspartate.
4.SynthesisofnucleotidesisCAREFULLYbalancedincells,duetothefactthatimbalancesin
quantityofnucleotidesisafactorincausingmutations.Mono,di,andtriphosphatesofthepurine
nucleotides(containingadenineorguanine)feedbackinhibitseveralstepsinthepathwayleadingto
theirsynthesis.
5.IMPisanintermediatethatisatthebranchpointbetweensynthesisofAMPandGMP.One
"balancing"actincontrollinglevelsofpurinenucleotidesisthatsynthesisofAMPrequiresGTPfor
energy.AMPalsoinhibitsitsownsynthesisbyfeedbackinhibition.Ontheotherhand,synthesisof
GMPrequiresATPforenergyandGMPfeedbackinhibitsitsownsynthesis,aswell.
6.Conversionofnucleosidemonophosphates(suchasAMP)tonucleosidediphosphates(suchas
ADP)iscatalyzedbyspecifickinases,butwewillrefertothemasnucleosidemonophosphate(or
nucleotide)kinases.Conversionofnucleosidediphosphatestonucleosidetriphosphates(suchasATP)
iscatalyzedbynucleosidediphosphokinase(NDPK).NDPKalsoconvertsallofthe
deoxyribonucleosidediphosphatestocorrespondingdeoxyribonucleosidetriphosphates.
7.Purinebreakdown(catabolism)goesthroughtheintermediateXanthine,whichisbrokendownto
uricacidandultimatelytoglyoxylateandurea.Uricacidcrystalsarethecausesofthepainfuldisease
knownasgout.

8.ATCaseistheprimaryregulatoryenzymeofpyrimidinebiosynthesis.Itprovidesbalancebetween
purinesandpyrimidines,sinceitisactivatedbyapurine(ATP)andinactivatedbyapyrimidine(CTP).
9.Pyrimidinesynthesisalsoincludesverysimpleprecursors,suchasaminoacids.Thefirstpyrimidine
nucleotidemadeisUMPandfromitUDP,UTP,andCTParemade.
10.Deoxyribonucleotides(buildingblocksofDNA)aremadefromribonucleotides(buildingblocksof
RNA)usingtheenzymeribonucleotidereductase(RNR).Notethattheprecursorribonucleotidesare
DIPHOSPHATESandthatthereactionsimplereducesthehydroxylgroupontheriboseringtoa
hydrogen,thusmakingdeoxyriboseasthesugaronadeoxyribonucleotide.
11.Thymidinenucleotidesaremadefromuridinenucleotides.Theprocessgoesasfollows:UDPgoes
todUDP.Then,severalreactionslater,dTTPismade.