The Molecules of Life
• Within cells, small organic molecules are joined
together to form larger molecules
• Macromolecules are large molecules composed
of thousands of covalently connected atoms
Most macromolecules are polymers, built from
monomers
• A polymer is a long molecule consisting of many
similar building blocks called monomers
• Three of the four classes of life’s organic
molecules are polymers:
– Carbohydrates
– Proteins
– Nucleic acids
The Synthesis and Breakdown of Polymers
• Monomers form larger molecules by condensation
reactions called dehydration reactions
• Polymers are disassembled to monomers by
hydrolysis, a reaction that is essentially the
reverse of the dehydration reaction
Short polymer
Unlinked monomer
Dehydration removes a water
molecule, forming a new bond
Longer polymer
Dehydration reaction in the synthesis of a polymer
Hydrolysis adds a water
molecule, breaking a bond
Hydrolysis of a polymer
The Diversity of Polymers
• Each cell has thousands of different kinds of
1
2 3
macromolecules
H
HO
• Macromolecules vary among cells of an organism,
vary more within a species, and vary even more
between species
• An immense variety of polymers can be built from
a small set of monomers
Lipids are a diverse group of hydrophobic
molecules
• Lipids are the one class of large biological
molecules that do not form polymers
• The unifying feature of lipids is having little or no
affinity for water
• Lipids are hydrophobic because they consist
mostly of hydrocarbons, which form nonpolar
covalent bonds
• The most biologically important lipids are fats,
phospholipids and steroids
Fats
• Fats are constructed from two types of smaller
molecules: glycerol and fatty acids
• Glycerol is a three-carbon alcohol with a hydroxyl
group attached to each carbon
• A fatty acid consists of a carboxyl group
attached to a long carbon skeleton
Fatty acid
(palmitic acid)
Glycerol
Dehydration reaction in the synthesis of a fat
• Fats separate from water because water
molecules form hydrogen bonds with 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
Ester linkage
Fat molecule (triacylglycerol)
• 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
• The major function of fats is energy storage
(a) Saturated fat
Structural
formula of a
saturated fat
molecule
Space-filling
model of
stearic acid,
a saturated
fatty acid
(b) Unsaturated fat
Structural
formula
of an
unsaturated
fat molecule
Space-filling
model of oleic
acid, an
unsaturated
fatty acid
Double bond
causes bending.
• Fats made from saturated fatty acids are called
saturated fats
• Most animal fats are saturated
• Saturated fats are solid at room temperature
• A diet rich in saturated fats may contribute to
cardiovascular disease through plaque deposits
Stearic acid
Saturated fat and fatty acid.
• Fats made from unsaturated fatty acids are called
unsaturated fats
• Plant fats and fish fats are usually unsaturated
• Plant fats and fish fats are liquid at room
temperature and are called oils
Oleic acid
cis double bond
causes bending
Unsaturated fat and fatty acid.
Phospholipids
• 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
Hydrophilic head
Hydrophobic tails
Choline
Phosphate
Glycerol
Fatty acids
(a) Structural formula
Hydrophilic
head
Hydrophobic
tails
(b) Space-filling model
(c) Phospholipid
symbol
(d) Phospholipid
bilayer
• When phospholipids are added to water, they selfassemble into a bilayer, with the hydrophobic tails
pointing toward the interior
• The structure of phospholipids results in a bilayer
arrangement found in cell membranes
• Phospholipids are the major component of all cell
membranes
Hydrophilic
head
Hydrophobic
tails
WATER
WATER
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
Proteins have many structures, resulting in a wide
range of functions
• Proteins account for more than 50% of the dry
mass of most cells
• Protein functions include structural support,
storage, transport, cellular communications,
movement, and defense against foreign
substances
• Enzymes are a type of protein that acts as a
catalyst, speeding up chemical reactions
• Enzymes can perform their functions repeatedly,
functioning as workhorses that carry out the
processes of life
Substrate
(sucrose)
Glucose
Enzyme
(sucrose)
Fructose
Defensive proteins
Function: Protection against disease
Example: Antibodies inactivate and help
destroy viruses and bacteria.
Antibodies
Virus
Bacterium
Storage proteins
Function: Storage of amino acids
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 for the developing embryo.
Ovalbumin
Amino acids
for embryo
Transport proteins
Function: Transport of substances
Examples: Hemoglobin, the iron-containing
protein of vertebrate blood, transports
oxygen from the lungs to other parts of the
body. Other proteins transport molecules
across cell membranes.
Transport
protein
Cell membrane
Hormonal proteins
Function: Coordination of an organism’s
activities
Example: Insulin, a hormone secreted by
the pancreas, causes other tissues to
take up glucose, thus regulating blood
sugar concentration.
High
blood sugar
Insulin
secreted
Normal
blood sugar
Receptor proteins
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.
Receptor
protein
Signaling molecules
Structural proteins
Function: Support
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 a
fibrous framework in animal connective
tissues.
Collagen
Connective tissue
60 m
Polypeptides
• Polypeptides are polymers of amino acids
• A protein consists of one or more polypeptides
Amino Acid Monomers
• Amino acids are organic molecules with carboxyl
and amino groups
• Amino acids differ in their properties due to
differing side chains, called R groups
• Cells use 20 amino acids to make thousands of
proteins
a carbon
Amino
group
Carboxyl
group
Nonpolar side chains; hydrophobic
Side chain
(R group)
Glycine
(Gly or G)
Methionine
(Met or M)
Alanine
(Ala or A)
Valine
(Val or V)
Phenylalanine
(Phe or F)
Leucine
(Leu or L)
Tryptophan
(Trp or W)
Isoleucine
(le or )
Proline
(Pro or P)
Polar side chains; hydrophilic
Serine
(Ser or S)
Threonine
(Thr or T)
Cysteine
(Cys or C)
Tyrosine
(Tyr or Y)
Asparagine
(Asn or N)
Glutamine
(Gln or Q)
Electrically charged side chains; hydrophilic
Basic (positively charged)
Acidic (negatively charged)
Aspartic acid Glutamic acid
(Asp or D)
(Glu or E)
Lysine
(Lys or K)
Arginine
(Arg or R)
Histidine
(His or H)
Amino Acids
Essential amino acids: An essential amino acid for an organism
is an amino acid that cannot be synthesized by the organism from
other available resources, and therefore must be supplied as part of
its diet.
Most of the plants and microorganism cells are able to use inorganic
compounds to make amino acids necessary for the normal growth.
Eight amino acids are generally regarded as essential for humans:
tryptophan, lysine, methionine, phenylalanine, threonine, valine,
leucine, isoleucine.
Two others, histidine and arginine are essential only in children. A
good memonic device for remembering these is "Private Tim Hall",
abbreviated as:
PVT TIM HALL:
Phenylalanine, Valine, Tryptophan
Threonine, Isoleucine, Methionine
Histidine, Arginine, Lysine, Leucine
Use of Amino Acids
• Aspartame (aspartyl-phenylalanine-1-methyl ester) is an
artificial sweetener.
• 5-HTP (5-hydroxytryptophan) has been used to treat
neurological problems associated with PKU
(phenylketonuria), as well as depression.
• Monosodium glutamate is a food additive to enhance
flavor.
Amino Acid Polymers
• Amino acids are linked by peptide bonds
• A polypeptide is a polymer of amino acids
• Polypeptides range in length from a few
monomers to more than a thousand
• Each polypeptide has a unique linear sequence of
amino acids
• Each polypeptide has a unique linear sequence of
amino acids, with a carboxyl end (C-terminus)
and an amino end (N-terminus)
Peptide bond
New peptide
bond forming
Side
chains
Backbone
Amino end
(N-terminus)
Peptide
bond
Carboxyl end
(C-terminus)
Protein Conformation and Function
• A functional protein consists of one or more
polypeptides twisted, folded, and coiled into a
unique shape
• The sequence of amino acids determines a
protein’s three-dimensional conformation
• A protein’s conformation determines its function
Antibody protein
Protein from flu virus
Four 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
Secondary
structure
Tertiary
structure
Quaternary
structure
Transthyretin
polypeptide
Transthyretin
protein
a helix
 pleated sheet
• Primary structure, the sequence of amino acids
in a protein, is like the order of letters in a long
word
• Primary structure is determined by inherited
genetic information
Primary structure
Amino
acids
1
10
5
Amino end
30
35
15
20
25
45
40
50
Primary structure of transthyretin
65
70
55
60
75
80
90
85
95
115
120
110
105
100
125
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
alpha helix and a folded structure called a beta
pleated sheet
Secondary structure
a helix
 pleated sheet
Hydrogen bond
 strand
Hydrogen
bond
Tertiary structure
Transthyretin
polypeptide
Hydrophobic
interactions and
van der Waals
interactions
Polypeptide
backbone
Hydrogen
bond
Disulfide bridge
Ionic bond
Quaternary structure
Transthyretin
protein
• Quaternary structure results when two or more
polypeptide chains form one macromolecule
• Hemoglobin is a globular protein consisting of
four polypeptides: two alpha and two beta chains
α-Keratin
• α-Keratin is a tough fibrous protein found in humans and
other mammals (hair, horns, wool, nails).
• * It is a helix of helices and is described as a coiled coil.
• * The basic structure has a pair of right-handed α-helices
wound around one another in a left-handed twist to form
super-twisted coiled coil)
• * It has a repeating structure that is rich in the amino
• acids Ala, Val, Leu, Ile, Met, and Phe.
• * Structure is cross-linked and stabilized by disulfide
• bonds.
Note that β-keratin (found in the feathers, scales, beaks,
claws of
birds/reptiles) rather has a stacked β sheet structure, and is
tougher than α-Keratin.
Polypeptide
chain
 Chains
Iron
Heme
Polypeptide chain
Collagen
a Chains
Hemoglobin
Sickle-Cell Disease: A Simple Change in
Primary Structure
• A slight change in primary structure can affect a
protein’s conformation and ability to function
• Sickle-cell disease, an inherited blood disorder,
results from a single amino acid substitution in the
protein hemoglobin
10 µm
Red blood Normal cells are
cell shape full of individual
hemoglobin
molecules, each
carrying oxygen.
10 µm
Red blood
cell shape
Fibers of abnormal
hemoglobin deform
cell into sickle
shape.
Figure 3.22
Sickle-cell
Normal
Primary
Structure
1
2
3
4
5
6
7
1
2
3
4
5
6
7
Secondary
and Tertiary
Structures
Quaternary
Structure
Function
Normal
hemoglobin
 subunit
a
Molecules do not
associate with one
another; each carries
oxygen.

a
5 m

Exposed hydrophobic region
Sickle-cell
hemoglobin
a
 subunit

Red Blood Cell
Shape
Molecules crystallized
into a fiber; capacity to
carry oxygen is reduced.

a
5 m
What Determines Protein Conformation?
• In addition to primary structure, physical and
chemical conditions can affect conformation
• Alternations in pH, salt concentration,
temperature, or other environmental factors can
cause a protein to unravel
• This loss of a protein’s native conformation is
called denaturation
• A denatured protein is biologically inactive
Denaturation
Normal protein
Denatured protein
Renaturation
The Protein-Folding Problem
• It is hard to predict a protein’s conformation from
its primary structure
• Most proteins probably go through several states
on their way to a stable conformation
• Chaperonins are protein molecules that assist the
proper folding of other proteins
Cap
Hollow
cylinder
Chaperonin
(fully assembled)
Polypeptide
Steps of Chaperonin
Action:
An unfolded polypeptide enters the
cylinder from one
end.
Correctly
folded
protein
The cap attaches, causing
the cylinder to change
shape in such a way that
it creates a hydrophilic
environment for the
folding of the polypeptide.
The cap comes
off, and the
properly folded
protein is released.
• Scientists use X-ray crystallography to
determine a protein’s conformation
X-ray
diffraction pattern
Photographic film
Diffracted X-rays
X-ray
source
X-ray
beam
Crystal
Nucleic acid
X-ray diffraction pattern
3D computer model
Protein
Nucleic acids store and transmit hereditary
information
• The amino acid sequence of a polypeptide is
programmed by a unit of inheritance called a gene
• Genes are made of DNA, a nucleic acid
The Roles of Nucleic Acids
• There are two types of nucleic acids:
– Deoxyribonucleic acid (DNA)
– Ribonucleic acid (RNA)
• DNA provides directions for its own replication
• DNA directs synthesis of messenger RNA (mRNA)
and, through mRNA, controls protein synthesis
• Protein synthesis occurs in ribosomes
DNA
Synthesis of
mRNA in the nucleus
mRNA
NUCLEUS
CYTOPLASM
mRNA
Movement of
mRNA into cytoplasm
via nuclear pore
Ribosome
Synthesis
of protein
Polypeptide
Amino
acids
The Structure of Nucleic Acids
• Nucleic acids are polymers called polynucleotides
• Each polynucleotide is made of monomers called
nucleotides
• Each nucleotide consists of a nitrogenous base,
a pentose sugar and a phosphate group
• The portion of a nucleotide without the phosphate
group is called a nucleoside
5 end
Sugar-phosphate backbone
(on blue background)
Nitrogenous bases
Pyrimidines
5C
3C
Nucleoside
Nitrogenous
base
Cytosine (C)
Thymine
(T, in DNA)
Uracil
(U, in RNA)
Purines
5C
Phosphate
group
3C
Sugar
(pentose)
Adenine (A)
Guanine (G)
(b) Nucleotide
3 end
Sugars
(a) Polynucleotide, or nucleic acid
Deoxyribose (in DNA)
(c) Nucleoside components
Ribose (in RNA)
5 end
Nucleoside
Nitrogenous
base
Phosphate
group
Nucleotide
3 end
Polynucleotide, or
nucleic acid
Pentose
sugar
5
3
3
5
Sugar-phosphate
backbones
Hydrogen bonds
Base pair joined
by hydrogen bonding
Nucleotide Monomers
• Nucleotide monomers are made up of
nucleosides and phosphate groups
• Nucleoside = nitrogenous base + sugar
• There are two families of nitrogenous bases:
– Pyrimidines have a single six-membered ring
– Purines have a six-membered ring fused to a
five-membered ring
• In DNA, the sugar is deoxyribose
• In RNA, the sugar is ribose
Nitrogenous bases
Pyrimidines
Cytosine
C
Thymine (in DNA) Uracil (in RNA)
U
T
Purines
Adenine
A
Guanine
G
Pentose sugars
Deoxyribose (in DNA)
Nucleoside components
Ribose (in RNA)
Nucleotide Polymers
• Nucleotide polymers are linked together, building a
polynucleotide
• Adjacent nucleotides are joined by covalent bonds
that form between the –OH group on the 3´ carbon of
one nucleotide and the phosphate on the 5´ carbon
on the next
• 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 DNA Double Helix
• A DNA molecule has two polynucleotides spiraling
around an imaginary axis, forming a double helix
• In the DNA double helix, the two backbones run in
opposite 5´ to 3´ directions from each other, an
arrangement referred to as antiparallel
• One DNA molecule includes many genes
• The nitrogenous bases in DNA form hydrogen
bonds in a complementary fashion: A always
with T, and G always with C
5 end
3 end
Sugar-phosphate
backbone
Base pair (joined by
hydrogen bonding)
Old strands
Nucleotide
about to be
added to a
new strand
5 end
New
strands
5 end
3 end
5 end
3 end
DNA and Proteins as Tape Measures of Evolution
• The linear sequences of nucleotides in DNA
molecules are passed from parents to offspring
• Two closely related species are more similar in
DNA than are more distantly related species
• Molecular biology can be used to assess
evolutionary kinship