Ch 5

Biological Macromolecules
and Lipids

Biology (General education course)

2015/10/12

Learning Objectives:
1. Describe the common properties of large biological
molecules
2. Identify and distinguish the four major classes of
macromolecules in terms of their monomers, structures,
chemical properties and major functions
3. Describe the four levels of protein structure and
explain how covalent & noncovalent bonds stabilize
biomolecules
4. Apply examples to explain the relationship between
amino acids and protein structure (e.g. Enzyme, sickle
cells)
5. Understand the profound impacts of genomics and
proteomics on the future of biology and other areas.
2

Lecture Outline
1. Macromolecules are polymers, built from
monomers
2. Carbohydrates serve as fuel and building material
3. Lipids are a diverse group of hydrophobic
molecules
4. Proteins include a diversity of structures, resulting
in a wide range of functions
5. Nucleic acids store, transmit, and help express
hereditary information
6. Genomics and proteomics have transformed
biological inquiry and applications
3

Macromolecules are polymers, built

from monomers

The Diversity of Mcromolecules

A polymer is a long molecule consisting of many similar
building blocks.
The repeating units that serve as building blocks are called monomers

Three of the four classes of lifes organic molecules are polymers:

Carbohydrates, Proteins, Nucleic acids
Each cell has thousands of different macromolecules, which vary among
cells of an organism, vary more within a species, and vary even more
between species.

Monomers

Polymer

The Synthesis and Breakdown of Polymers

(a) Dehydration reaction: synthesizing a polymer

Dehydration reaction/
Condensation reaction

Hydrolysis
Enzymes required

Short polymer

Unlinked monomer

Dehydration removes
a water molecule,
forming a new bond.

Longer polymer
(b) Hydrolysis: breaking down a polymer
2

Diverse Polymers

Hydrolysis adds
a water molecule,
breaking a bond.

Fig 5.2

Carbohydrates serve as fuel and

building material

(Carbonyl group)

Sugars

Aldoses (Aldehyde Sugars)

Ketoses (Ketone Sugars)

Trioses: 3-carbon sugars (C3H6O3)

Monosaccharides
molecular formulas:
(CH2O)n
Glucose (C6H12O6) :

Glyceraldehyde

Dihydroxyacetone

Pentoses: 5-carbon sugars (C5H10O5)

the most common

aldose
classification
The location of the
carbonyl group:
aldose
ketose

ketose

D- form

number of carbons

Ribose

Ribulose

Hexoses: 6-carbon sugars (C6H12O6)

epimers at C-4
dextrose = D-(+)-Glc
Glucose

Galactose

Fructose

Figure 5.3 The structure and

classification of some monosaccharides

(a) Linear and ring forms of glucose

-
(~ 2/3)

anomer,

anomeric carbon
10

-D-glucopyranose

-D-glucopyranose

11

11

The covalent bond joins two monosaccharides is

Disaccharide

called a glycosidic linkage

nonreducing end

Gal(14)Glc

reducing end

reducing sugar
hydrolyzed by lactase (human), -galactosidase (bacteria)
Lactose intolerance
12

Examples of disaccharide synthesis

(glycosidic linkage)
14
glycosidic
1 linkage 4

Glucose

Glucose

(a) Dehydration reaction in the synthesis of maltose

Maltose

reducing sugar

12
glycosidic
1 linkage 2

Glucose

Fructose

(b) Dehydration reaction in the synthesis of sucrose

Sucrose

non-reducing sugar 13

Polysaccharides (Glycans)
Serve as storage and structural roles
The architecture and function of a polysaccharide
are determined by its sugar monomers and the
positions of its glycosidic linkages

14

Storage Polysaccharides
Starch, polymers of glucoses in plants: (14)
amyloseThe simplest form, & amylopectin
Plants store surplus starch as granules within chloroplasts
and other plastids

Glycogen, polymers of glucoses in animals

Is stored mainly in liver and muscle cells
They are hydrolyzed to release glucose when the demand
for sugar increases

Structural Polysaccharides
Cellulose, polymers of glucoses in plant cell walls.
but the glycosidic linkages differ from starch; (14)
Chitin, in the exoskeleton of arthropods and cell walls
of many fungi
15

Amylopectin, glycogen: (14) & (16) linkage,

branched
(16)

Amylases
( glucose monomer)

(14)

Cellulases
( glucose monomer)

Cellulose:
(14)
16

Figure 5.6

Storage structures
(plastids)
containing starch
granules in a potato
tuber cell

largely helical
Amylose (unbranched)

Amylopectin Glucose
(somewhat monomer
branched)
50 m

(a) Starch
Glycogen
granules in
muscle
tissue
Cell
wall

1 m
(b) Glycogen
Cellulose microfibrils
in a plant cell wall

Plant cell,
10 m
surrounded
by cell wall

Glycogen (branched)

Microfibril

Cellulose molecule (unbranched)

Hydrogen bonds

0.5 m
(c) Cellulose

18

What would happen if a cow were given antibiotics

that killed all the prokaryotes in its stomach?
The cellulose in human food passes through the digestive
tract as insoluble fiber
Many herbivores, from cows to termites, have symbiotic
relationships with some microbes that use enzymes
(cellulases) to digest cellulose

19

Figure 5.8

The structure
of the chitin
monomer

N-acetylglucosamine
units, in -1,4 linkage

Chitin, embedded in proteins,

forms the exoskeleton of
arthropods .

is used to
Chitin
make a strong
and flexible
surgical
thread.

Chitin also provides

structural support for the
cell walls of many fungi

20

Glycoproteins

N-link (Asn) & O-link (Ser)

21

proteoglycan
glycosaminoglycan, GAG )

heparin

proteoglycan
glycosaminoglycanGAG
(Hyaluronic acid)

23

Lipids are a diverse group of

hydrophobic molecules

24

Lipid Functions
Energy storage
Cell membrane
Signaling molecule

25

Lipids
the one class of large biological molecules that does not
include true polymers
consist mostly of hydrocarbons; hydrophobic
The most biologically important lipids are fats, phospholipids,
and steroids

26

 Fats separate from water because water

molecules hydrogen-bond to each other and
exclude the fats
In a fat, three fatty acids are joined to glycerol
by an ester linkage, creating a triacylglycerol,
or triglyceride
The fatty acids in a fat can be all the same or of
two or three different kinds
Fatty acids vary in length (number of carbons)
and in the number and locations of double bonds
Saturated fatty acids have the maximum number
of hydrogen atoms possible and no double bonds
Unsaturated fatty acids have one or more double
bonds

Fats
Fats are
constructed
from glycerol
and fatty acids
A fatty acid
consists of a
carboxyl group
attached
to a long carbon
skeleton

Fig 5.10
The synthesis and
structure of a fat, or
triacylglycerol

Fatty acid
(in this case, palmitic acid)

Glycerol
(a) One of three dehydration reactions in the synthesis of
a fat
Ester linkage

(b) Fat molecule (triacylglycerol)

(,or triglyceride

28

Fatty acids vary in length (number of carbons) and

in the number and locations of double bonds
(a) Saturated fat
Structural
formula of a
saturated fat
molecule

(b) Unsaturated fat

Structural
formula of an
unsaturated fat
molecule

Cis double bond

causes bending.
Space-filling model of stearic
acid, a saturated fatty acid
Figure 5.11

Space-filling model of oleic

acid, an unsaturated fatty acid

29

 monounsaturated fatty acids, MUFA

polyunsaturated fatty acids, PUFA

Nomenclatures of fatty acids

Trans-fatty acid

cis-fatty acid

30

 Fats made from saturated fatty acids are called

saturated fats and are solid at room temperature
Most animal fats are saturated
Fats made from unsaturated fatty acids are
called unsaturated fats or oils and are liquid at room
temperature
Plant fats and fish fats are usually unsaturated
Essential fatty acids
These must be supplied in the diet, not
synthesized in the human body
include the omega-3 fatty acids, required for
normal growth, and thought to provide protection
against cardiovascular disease.

 The major function of fats is energy storage

Humans and other mammals store their longterm food reserves in adipose cells
Adipose tissue also cushions vital organs and
insulates the body

 A diet rich in saturated fats may contribute to

cardiovascular disease through plaque deposits
Hydrogenation is the process of converting
unsaturated fats to saturated fats by adding
hydrogen
Hydrogenating vegetable oils also creates
unsaturated fats with trans double bonds
These trans fats may contribute more than
saturated fats to cardiovascular disease

Successful diets usually involve three things:

decreasing the amounts of carbohydrates
and fats; exercise; and behavior modification.

Hydrophobic tails

Hydrophilic head

Phospholipids
Choline
Phosphate
Glycerol

In a phospholipid, two
fatty acids and a
phosphate group are
attached to glycerol
The two fatty acid tails
are hydrophobic, but the
phosphate group and its
attachments form a
hydrophilic head

Fatty acids
Hydrophilic
head
Hydrophobic
tails

(a) Structural formula

(b) Space-filling model

(c) Phospholipid symbol

Fig 5.12 The structure of a phospholipid. 34

 When phospholipids are added to water, they

self-assemble into double-layered structures
called bilayers
At the surface of a cell, phospholipids are also
arranged in a bilayer, with the hydrophobic tails
pointing toward the interior
The structure of phospholipids results in a
bilayer arrangement found in cell membranes
The existence of cells depends on phospholipids

 The structure of phospholipids results in a bilayer

arrangement found in cell membranes
36

Steroids
Steroids are lipids characterized by a carbon skeleton
consisting of four fused rings
Cholesterol, an important steroid, is a component in
animal cell membranes
Although cholesterol is essential in animals, high levels
in the blood may contribute to cardiovascular disease
Fig 5.14 Cholesterol, a steroid

37

Cholesterol and Membrane Fluidity

Sex hormones

39

Proteins include a diversity of structures,

resulting in a wide range of functions

40

 Proteins are all constructed from the same set of

20 amino acids
Polypeptides are unbranched polymers built
from these amino acids
A protein is a biologically functional molecule
that consists of one or more polypeptides
Proteins account for more than 50% of the dry
mass of most cells.
Diverse protein functions

Classification

42

An overview of protein functions

Enzymatic proteins

Defensive proteins

Function: Selective acceleration of

chemical reactions
Example: Digestive enzymes catalyze the
hydrolysis of bonds in food molecules.

Function: Protection against disease

Example: Antibodies inactivate and help destroy
viruses and bacteria.
Antibodies

Enzyme

Virus

Bacterium

Storage proteins

Transport proteins

Function: Storage of amino acids

Function: Transport of substances

Examples: Casein, the protein of milk, is the major

source of amino acids for baby mammals.
Plants have storage proteins in their seeds.
Ovalbumin is the protein of egg white, used as
an amino acid source or the developing embryo.

Examples: Hemoglobin, the iron-containing

protein of ertebrate blood, transports oxygen
from the lungs to other parts of the body. Other
proteins transport molecules across
cell membranes.
Transport
protein

Ovalbumin

Figure 5.15

Amino acids
for embryo

Cell membrane

Figure 5.15-b

Hormonal proteins

Receptor proteins

Function: Coordination of an organisms activities

Example: Insulin, a hormone secreted by the
pancreas, causes other tissues to take up glucose,
thus regulating blood sugar concentration

Function: Response of cell to chemical stimuli

Example: Receptors built into the membrane of a
nerve cell detect signaling molecules released by
other nerve cells.

High
blood sugar

Insulin
secreted

Normal
blood sugar

Receptor
protein

Signaling
molecules

Contractile and motor proteins

Structural proteins

Function: Movement

Function: Support

Examples: Motor proteins are responsible for the

undulations of cilia and flagella. Actin and myosin
proteins are responsible for the contraction of
muscles.

Examples: Keratin is the protein of hair, horns,

feathers, and other skin appendages. Insects and
spiders use silk fibers to make their cocoons and
webs,respectively. Collagen and elastin proteins
provide afibrous framework in animal connective
tissues.

Actin

Myosin
Collagen

Muscle tissue

100 m

Connective
tissue

60 m

 Enzymes are a type of protein that acts as a catalyst to

speed up chemical reactions
Enzymes can perform their functions repeatedly, functioning
as workhorses that carry out the processes of life.
Active site

Substrate
(sucrose)

Glucose
OH

Enzyme
(sucrase)

H2O

Products
HO
Fructose

The catalytic cycle

of an enzyme

Amino Acid Monomers

Amino acids are
organic molecules
with carboxyl and
amino groups
Amino acids differ in
side chains, called R
groups

Side chain (R group)

carbon

Amino
group

Carboxyl
group

Figure 5.16
Nonpolar side chains; hydrophobic
Side chain
(R group)

Glycine
(Gly or G)

Alanine
(Ala or A)

Methionine
(Met or M)

Isoleucine
(Ile or I)

Leucine
(Leu or L)

Valine
(Val or V)

Phenylalanine
(Phe or F)

Tryptophan
(Trp or W)

Proline
(Pro or P)

Polar side chains; hydrophilic

Serine
(Ser or S)

Threonine
(Thr or T)

Cysteine
(Cys or C)

Electrically charged side chains; hydrophilic

Tyrosine
(Tyr or Y)

Asparagine
(Asn or N)

Glutamine
(Gln or Q)

Basic (positively charged)

Acidic (negatively charged)

Aspartic acid
(Asp or D)

Glutamic acid
(Glu or E)

Lysine
(Lys or K)

Arginine
(Arg or R)

Histidine
(His or H)

Polypeptides (Amino Acid Polymers)

Amino acids are linked by covalent bonds
called peptide bonds
A polypeptide is a polymer of amino acids
Polypeptides range in length from a few to
more than a thousand monomers
Each polypeptide has a unique linear
sequence of amino acids, with a carboxyl end
(C-terminus) and an amino end (N-terminus)

Making a
polypeptide chain
Figure 5.17

Peptide bond
Peptide bond

New peptide
bond forming

Side chains

Back-bone

Amino end
(N-terminus)

Peptide
bond

Carboxyl end
(C-terminus)

Protein Structure and Function

The specific activities of proteins result from their
intricate three-dimensional architecture
A functional protein consists of one or more
polypeptides precisely twisted, folded, and coiled
into a unique shape
The sequence of amino acids determines a
proteins three-dimensional structure
A proteins structure determines its function
The function of a protein usually depends on its
ability to recognize and bind to some other
molecule

Figure 5.16

Structure of a protein, the enzyme lysozyme

Target
molecule
Groove

(a) A ribbon model

Groove

(b) A space-filling model

(c) A wireframe model

Figure 5.17

Antibody protein

Protein from flu virus

Levels of Protein Structure

The primary structure of a protein is its
unique sequence of amino acids
Secondary structure, found in most proteins,
consists of coils and folds in the polypeptide
chain
Tertiary structure is determined by
interactions among various side chains (R
groups)
Quaternary structure results when a protein
consists of multiple polypeptide chains

Primary structure

Primary structure
the sequence of
amino acids in a
protein
is determined by
inherited genetic
information

Amino
acids

Amino end

Primary structure of transthyretin

Carboxyl end

 The coils and folds of secondary structure

result from hydrogen bonds between
repeating constituents of the polypeptide
backbone
Typical secondary structures are a coil called
an helix and a folded structure called a
pleated sheet

 Tertiary structure, the overall shape of a

polypeptide, results from interactions between
R groups, rather than interactions between
backbone constituents
These interactions include hydrogen bonds,
ionic bonds, hydrophobic interactions, and
van der Waals interactions
Strong covalent bonds called disulfide bridges
may reinforce the proteins structure

Four Levels of Protein Structure

Secondary
structure

Tertiary
structure

Quaternary
structure

Hydrogen bond
helix

pleated sheet
strand

Hydrogen
bond

Transthyretin
protein
Transthyretin
polypeptide

Secondary structure
helix

pleated sheet

Hydrogen bond

strand, shown as a
flat arrow pointing
toward the carboxyl end

Hydrogen bond

Figure 5.20c

Figure 5.20e

Tertiary structure
Transthyretin
polypeptide

Hydrogen
bond

Disulfide
bridge

Polypeptide
backbone

Hydrophobic
interactions and
van der Waals
interactions
Ionic bond

 Quaternary structure results when two or more

polypeptide chains form one macromolecule
Collagen is a fibrous protein consisting of three
polypeptides coiled like a rope.
Hemoglobin is a globular protein consisting of four
polypeptides: two alpha and two beta chains.

Collagen-- triple helix structure

Transthyretin protein
(four identical polypeptides)

Heme
Iron
subunit
subunit

subunit

subunit

Hemoglobin

Sickle-Cell Disease: A Change in Primary

Structure
A slight change in primary structure can affect
a proteins structure and ability to function
Sickle-cell disease, an inherited blood
disorder, results from a single amino acid
substitution in the protein hemoglobin

A single amino acid substitution in a protein causes sickle-cell disease

Sickle-cell hemoglobin

Normal hemoglobin

Primary
Structure

1
2
3
4
5
6
7

Secondary
and Tertiary
Structures

Quaternary
Structure

Function
Molecules do not
associate with one
another; each carries
oxygen.

Normal
hemoglobin

subunit

Red Blood
Cell Shape

10 m

1
2
3
4
5
6
7

Exposed
hydrophobic
region

Molecules interact with

one another and
crystallize into a fiber;
capacity to carry
oxygen is reduced.

Sickle-cell
hemoglobin

subunit

10 m

What Determines Protein Structure?

Alterations in pH, salt concentration, temperature, or other
environmental factors can cause a protein to unravel
This loss of a proteins native structure is called
denaturation (2, 3, 4 )
A denatured protein is biologically inactive

Figure 5.22

Denaturation
and renaturation
of a protein.

Protein Folding in the Cell

It is hard to predict a proteins
structure from its primary structure
Most proteins probably go through
several stages on their way to a
stable structure
Chaperonins are protein
molecules that assist the proper
folding of other proteins

Diseases such as Alzheimers,

Parkinsons, and mad cow
disease are associated with
misfolded proteins

Cap

Hollow
cylinder

Chaperonin
(fully assembled)
Fig 5.23

Figure 5.23 A chaperonin in action.

Polypeptide

Correctly
folded
protein

Steps of Chaperonin 2 The cap attaches, causing 3 The cap comes

Action:
the cylinder to change
off, and the
1 An unfolded polyshape in such a way that
properly folded
peptide enters the
it creates a hydrophilic
protein is
cylinder from
environment for the
released.
one end.
folding of the polypeptide.

 Scientists use X-ray crystallography to

determine a proteins structure
Another method is nuclear magnetic resonance
(NMR) spectroscopy, which does not require
protein crystallization
Bioinformatics is another approach to prediction
of protein structure from amino acid sequences

Determine a
proteins
structure
X-ray
crystallography
nuclear magnetic
resonance (NMR)
spectroscopy
Bioinformatics

Figure 5.24 Inquiry: What

can the 3-D shape of the
enzyme RNA polymerase II
tell us about its function?

EXPERIMENT
Diffracted
X-rays
X-ray
source X-ray
beam
Crystal

Digital detector

X-ray diffraction
pattern

RESULTS
RNA

DNA

RNA
polymerase II

Nucleic acids store, transmit, and

help express hereditary information

69

Nucleic acids store, transmit, and help

express hereditary information
The amino acid sequence of a polypeptide is
programmed by a unit of inheritance called
a gene
Genes consist of DNA, a nucleic acid made of
monomers called nucleotides
There are two types of nucleic acids
Deoxyribonucleic acid (DNA)
Ribonucleic acid (RNA)

The Roles of Nucleic Acids

DNA provides directions for its own replication
DNA directs synthesis of messenger RNA (mRNA)
and, through mRNA, controls protein synthesis
This process is called gene expression
Each gene along a DNA molecule directs synthesis
of a messenger RNA (mRNA)
The mRNA molecule interacts with the cells
protein-synthesizing machinery to direct
production of a polypeptide
The flow of genetic information can be
summarized as DNA RNA protein

DNA: Genetic materials

RNA: Gene expression
r-RNA, mRNA, rRNA,
& others
(some as enzymes)

DNA

1 Synthesis of
mRNA

mRNA

DNA RNA Protein

NUCLEUS

CYTOPLASM
mRNA
2 Movement of
mRNA into
cytoplasm

Ribosome

3 Synthesis
of protein

Polypeptide
Figure 5.25-3

Amino
acids

The Components of Nucleic Acids

Nucleotide Monomers
Nucleoside = nitrogenous base + sugar
There are two families of nitrogenous bases
Pyrimidines (cytosine, thymine, and uracil) have
a single six-membered ring
Purines (adenine and guanine) have a sixmembered ring fused to a five-membered ring
In DNA, the sugar is deoxyribose; in RNA, the sugar
is ribose
Nucleotide = nucleoside + phosphate group

Components of nucleic acids

Nitrogenous bases

Sugar-phosphate backbone
5 end

Pyrimidines
5C
3C

Nucleoside
Nitrogenous
base

Cytosine (C) Thymine (T, in DNA) Uracil (U, in RNA)

Purines

5C

1C

5C
3C

Phosphate
group

3C

Sugar
(pentose)
Guanine (G)

Adenine (A)

(b) Nucleotide
Sugars

3 end

(a)

Polynucleotide,
or nucleic acid
Deoxyribose (in DNA)

Figure 5.26
(c)

Ribose (in RNA)

Nucleoside components

Nucleotide Polymers
Nucleotides are linked together to build a
polynucleotide
Adjacent nucleotides are joined by a
phosphodiester linkage, which consists of a
phosphate group that links the sugars of two
nucleotides
These links create a backbone of sugar-phosphate
units with nitrogenous bases as appendages
The sequence of bases along a DNA or mRNA
polymer is unique for each gene

The Structures of DNA and RNA Molecules

DNA molecules have two polynucleotides spiraling
around an imaginary axis, forming a double helix
The backbones run in opposite 5 3 directions
from each other, an arrangement referred to as
antiparallel
One DNA molecule includes many genes
Only certain bases in DNA pair up and form
hydrogen bonds: adenine (A) always with thymine
(T), and guanine (G) always with cytosine (C)
This is called complementary base pairing
This feature of DNA structure makes it possible to
generate two identical copies of each DNA
molecule in a cell preparing to divide

 RNA, in contrast to DNA, is single stranded

Complementary pairing can also occur
between two RNA molecules or between parts
of the
same molecule
In RNA, thymine is replaced by uracil (U) so
A and U pair
While DNA always exists as a double helix,
RNA molecules are more variable in form

Figure 5.27

The structures of DNA and tRNA molecules

5

Sugar-phosphate
backbones
Hydrogen bonds

Base pair joined

by hydrogen
bonding

(a) DNA

Base pair joined

by hydrogen bonding

(b) Transfer RNA

Genomics and proteomics have

transformed biological inquiry and
applications

Figure 5.26

MAKE CONNECTIONS
Contributions of Genomics and Proteomics to Biology
Paleontology

Evolution

Hippopotamus

Medical Science

Short-finned pilot whale

Conservation Biology

Species
Interactions

80

Genomics and proteomics have transformed

biological inquiry and applications
Once the structure of DNA and its relationship to
amino acid sequence was understood, biologists
sought to decode genes by learning their base
sequences
The first chemical techniques for DNA sequencing were
developed in the 1970s and refined over the next 20
years
It is enlightening to sequence the full complement of
DNA in an organisms genome
The rapid development of faster and less expensive
methods of sequencing was a side effect of the Human
Genome Project
Many genomes have been sequenced, generating
reams of data

 Bioinformatics uses computer software and

other computational tools to deal with the
data resulting from sequencing many
genomes
Analyzing large sets of genes or even
comparing whole genomes of different
species is called genomics
A similar analysis of large sets of proteins
including their sequences is called proteomics

DNA and Proteins as Tape Measures

of Evolution
Sequences of genes and their protein products
document the hereditary background of an
organism
Linear sequences of DNA molecules are
passed from parents to offspring
We can extend the concept of molecular
genealogy to relationships between species
Molecular biology has added a new measure
to the toolkit of evolutionary biology

DNA and Proteins as Tape Measures

of Evolution
Human

Rhesus
monkey

Gibbon

Summary
An immense variety of biological polymers with
diverse functions can be built from a small number
of specific class of monomers.
Carbohydrates, lipids, proteins, and nucleic acids
are four major categories of biological
macromolecules in living organisms.
Can you compare the common and diverse
characteristics of the four major large biological
molecules in terms of structure and function?
Importance of genomics and proteomics


(1)

(2)
DNA
double helix Helix Sheet
conformation

(3)

(4)
(5)