BIOLOGICAL MACROMOLECULES

 Foods such as bread, fruit and cheese are

rich sources of biological macromolecules. 1
 Introduction
 Biological macromolecules are large molecules,
necessary for life, that are built from smaller organic
molecules.
 There are four major classes of biological
macromolecules (carbohydrates, lipids, proteins, and
nucleic acids); each is an important cell component and
performs a wide array of functions.
 Combined, these molecules make up the majority of a
cell’s dry mass.
 Biological macromolecules are organic, meaning they
contain carbon. In addition, they may contain hydrogen,
oxygen, nitrogen, and additional minor elements. 2
 Synthesis of biological macromolecules
 Most macromolecules are made from single subunits, or
building blocks, called monomers. The monomers combine
with each other using covalent bonds to form larger molecules
known as polymers. In doing so, monomers release water
molecules as byproducts.
 This type of reaction is known as dehydration synthesis,
which means “to put together while losing water.”

Figure: In the dehydration synthesis reaction depicted above, two

molecules of glucose are linked together to form the dissacharide
3
maltose. In the process, a water molecule is formed.
Degradation of biological macromolecules
 Polymers are broken down into monomers in a process
known as hydrolysis, which means “to split water,” a reaction
in which a water molecule is used during the breakdown.
 During these reactions, the polymer is broken into two
components: one part gains a hydrogen atom (H+) and the
other gains a hydroxyl molecule (OH–) from a split water
molecule.

Figure: In the hydrolysis reaction shown here, the disaccharide

maltose is broken down to form two glucose monomers with
4
the addition of a water molecule.
 Role of enzymes in dehydration
and hydrolysis reactions
 Dehydration and hydrolysis reactions are catalyzed, or
“sped up,” by specific enzymes; dehydration reactions
require energy, while hydrolysis reactions release energy.
 These reactions are similar for most macromolecules, but
each monomer and polymer reaction is specific for its class.
 For example, in our bodies, food is hydrolyzed, or broken
down, into smaller molecules by catalytic enzymes in the
digestive system. This allows for easy absorption of nutrients
by cells in the intestine.
 Each macromolecule is broken down by a specific enzyme.
For instance, carbohydrates are broken down by amylase,
sucrase, lactase, or maltase. 5
 Role of enzymes (contd.)

Maltase

 Proteins are broken down by the enzymes pepsin and

peptidase, and by hydrochloric acid. Lipids are broken down by
lipases. Breakdown of these macromolecules provides energy
6
for cellular activities.
 Macromolecule: Carbohydrates
 To lose weight, some individuals adhere to “low-carb” diets.
Athletes, in contrast, often “carb-load” before important
competitions to ensure that they have enough energy to
compete at a high level.
 Carbohydrates are, in fact, an essential part of our diet; grains,
fruits, and vegetables are all natural sources of carbohydrates.
 Carbohydrates also have other important functions in humans,
animals, and plants.
 Carbohydrates can be represented by the formula (CH2O)n,
where n is the number of carbons in the molecule.
 In other words, the ratio of carbon to hydrogen to oxygen is
1:2:1 in carbohydrate molecules.
 This formula also explains the origin of the term “carbohydrate”:
the components are carbon (“carbo”) and the components of
water (hence, “hydrate”).
 Carbohydrates are classified into three subtypes: monosaccha-
rides, disaccharides, and polysaccharides. 7
 Monosaccharides
 Monosaccharides (mono = “one”; sacchar = “sweet”) are
simple sugars, the most common of which is glucose.
 In monosaccharides, the number of carbons usually
ranges from three to seven.
 Most monosaccharide names end with the suffix -ose.
 If the sugar has an aldehyde group [the functional group
with the structure R-CHO], it is known as an aldose.
 If the sugar has a ketone group [the functional group
with the structure RC(=O)R‘], it is known as a ketose.
 Depending on the number of carbons in the sugar, they
also may be known as trioses (three carbons), pentoses
(five carbons), and or hexoses (six carbons). 8
 Monosaccharides (contd.)

 Monosaccharides are classified based on the position of their

carbonyl group and the number of carbons in the backbone.
Aldoses have a carbonyl group (indicated in green) at the end
of the carbon chain, and ketoses have a carbonyl group in the
9
middle of the carbon chain.
 Monosaccharides (contd.)
The chemical formula
for glucose is C6H12O6.
In humans, glucose is
an important source of
energy.
Glucose and galactose
are aldoses, and
fructose is a ketose.
During cellular respiration, energy is released from glucose, and
that energy is used to help make adenosine triphosphate (ATP).
Plants synthesize glucose using carbon dioxide and water, and
glucose in turn is used for energy requirements for the plant.
Excess glucose is often stored as starch that is catabolized (the
breakdown of larger molecules by cells) by humans and other
10
animals that feed on plants.
 Monosaccharides (contd.)
Galactose (part of lactose, or milk sugar) and fructose (found in
sucrose, in fruit) are other common monosaccharides.
Although glucose, galactose, and fructose all have the same
chemical formula (C6H12O6), they differ structurally and chemically
(and are known as isomers) because of the different arrangement
of functional groups around the asymmetric carbon.
All of these monosaccharides have more than one asymmetric
carbon. An asymmetric carbon atom (chiral carbon) is a
carbon atom that is attached to four different types of atoms or
groups of atoms.
Monosaccharides can exist as a linear chain or as ring-shaped
molecules; in aqueous solutions they are usually found in ring
forms. Glucose in a ring form can have two different arrangements
of the hydroxyl group (OH) around the anomeric carbon (carbon 1
that becomes asymmetric in the process of ring formation). 11
 Monosaccharides (contd.)
Glucose is present in nature in two different molecular
arrangements known as isomers. The two isomers of glucose
are named L-glucose and D-glucose. Dextrose is D-glucose
and may be referred to as dextrose or glucose because
dextrose is actually a form of glucose that is found naturally in
foods such as fruit and honey.
Researchers from a company
supported by NASA found that L-
glucose and D-glucose taste
exactly the same, but only D-
glucose is metabolized quickly to
produce energy. L-glucose is
metabolized slowly and considered
as a low-calorie sweetener. It
turned out that L-glucose is too
expensive to produce. 12
 Monosaccharides (contd.)

If the –OH group is

below carbon
number 1 in the
sugar, it is said to
be in the α-sugar,
and if -OH group is
above the plane, it
is said to be in the
β-sugar. 13
 Monosaccharides (contd.)

 Although fructose has 6 carbons, it forms five-membered ring

instead of six-membered ring like as ribose (5-C). 14
 Disaccharides
 Disaccharides (di = “two”) form when two monosaccharides
undergo a dehydration reaction.
 During this process, the hydroxyl group of one
monosaccharide combines with the hydrogen of another
monosaccharide, releasing a molecule of water and forming a
covalent bond.
 A covalent bond formed between a carbohydrate molecule and
another molecule (in this case, between two mono-
saccharides) is known as a glycosidic bond.
 Glycosidic bonds (also called glycosidic linkages) can be of
the alpha or the beta type.
 Common disaccharides include lactose, maltose, and sucrose.
 Lactose is a disaccharide consisting of the monomers glucose
and galactose. It is found naturally in milk. 15
 Disaccharides (contd.)
The most common disaccharide is sucrose, or table sugar. By
convention, the carbon atoms in a monosaccharide are numbered
from the terminal carbon closest to the carbonyl group.
In sucrose, a glycosidic linkage is formed between carbon 1 in
glucose and carbon 2 in fructose.
 Disaccharides (contd.)

Maltose (grain sugar) = glucose + glucose

Lactose (milk sugar) = glucose + galactose

17
Galactose
 Polysaccharides
 A long chain of monosaccharides linked by glycosidic bonds is
known as a polysaccharide (poly = “many”). The chain may be
branched or unbranched, and it may contain different types of
monosaccharides. The Mw may be 100,000 daltons or more
depending on the number of monomers joined.
 Starch, glycogen, cellulose, and chitin are primary examples of
polysaccharides.
 Starch is the stored form of sugars in plants and is made up of a
mixture of amylose and amylopectin (both polymers of glucose).
 Plants are able to synthesize glucose, and the excess glucose,
beyond the plant’s immediate energy needs, is stored as starch in
different plant parts, including roots and seeds.
 The starch in the seeds provides food for the embryo as it
germinates and can also act as a source of food for humans and
animals. The starch that is consumed by humans is broken down by
enzymes, such as salivary amylases, into smaller molecules, such
as maltose and glucose. The cells can then absorb the glucose. 18
 Amylose is composed
of unbranched chains
of glucose monomers
connected by α 1-4
glycosidic linkages.
 Amylopectin is
composed of
branched chains of
glucose monomers
connected by α 1-4
and α 1-6 glycosidic
linkages.
 Because of the way
the subunits are
joined, the glucose
chains have a helical
19
structure.
 Glycogen and Cellulose
 Glycogen is similar in structure to amylopectin but more
highly branched. It is the storage form of glucose in humans
and other vertebrates, and is made up of monomers of
glucose.
 Glycogen is the animal equivalent of starch and is a highly
branched molecule usually stored in liver and muscle cells.
 Whenever blood glucose levels decrease, glycogen is broken
down to release glucose in a process known as
glycogenolysis.
 Cellulose is the most abundant natural biopolymer. The cell
wall of plants is mostly made of cellulose; this provides
structural support to the cell.
 Wood and paper are mostly cellulosic in nature. Cellulose is
made up of glucose monomers that are linked by β 1-4
20
glycosidic bonds.
 In cellulose, glucose monomers are linked in unbranched
chains by β 1-4 glycosidic linkages. Because of the way
the glucose subunits are joined, every glucose monomer
is flipped relative to the next one resulting in a linear,
fibrous structure.

21
Every other glucose monomer in cellulose is flipped over, and
the monomers are packed tightly as extended long chains. This
gives cellulose its rigidity and high tensile strength - which is so
important to plant cells.
While the β 1-4 linkage cannot be broken down by human
digestive enzymes, herbivores such as cows, buffalos, and
horses are able, with the help of the specialized flora in their
stomach, to digest plant material that is rich in cellulose and
use it as a food source.
In these animals, certain species of bacteria and protists reside
in the rumen (part of the digestive system of herbivores) and
secrete the enzyme cellulase.
Termites are also able to break down cellulose because of the
presence of other organisms in their bodies that secrete
cellulases 22
 Chitin
 Carbohydrates serve various functions in different animals.
Arthropods (insects, crustaceans, and others) have an
outer skeleton, called the exoskeleton, which protects their
internal body parts (as seen in the bee in figure below).
 This exoskeleton is made of the
biological macromolecule chitin,
which is a polysaccharide-
containing nitrogen.
 Chitin is made of repeating units
of N-acetyl-β-d-glucosamine, a
modified sugar. Chitin is also a
major component of fungal cell
23
walls.
 Benefits of Carbohydrates
Carbohydrates should be supplemented with proteins, vitamins,
and fats to be parts of a well-balanced diet.
Carbohydrates contain soluble and insoluble elements; the
insoluble part is known as fiber, which is mostly cellulose.
Fiber has many uses; it promotes regular bowel movement
by adding bulk, and it regulates the rate of consumption of
blood glucose.
Fiber also helps to remove excess cholesterol from the body:
fiber binds to the cholesterol in the small intestine, then
attaches to the cholesterol and prevents the cholesterol
particles from entering the bloodstream, and then cholesterol
exits the body via the feces.
Fiber-rich diets also have a protective role in reducing the
occurrence of colon cancer.
 Macromolecule: Lipids
 Lipids include a diverse group of compounds that are largely
nonpolar in nature. This is because they are hydrocarbons
that include mostly nonpolar carbon-carbon or carbon-
hydrogen bonds.
 Non-polar molecules are hydrophobic (“water fearing”), or
insoluble in water.
 Lipids perform many different functions in a cell. Cells store
energy for long-term use in the form of fats.
 Lipids also provide insulation from the environment for plants
and animals.
 Lipids are also the building blocks
of many hormones and are an
important constituent of all cellular
membranes.
 Lipids include fats, oils, waxes,
25
Hydrophobic lipids in the fur of aquatic
phospholipids, and steroids. mammals, such as this river otter.
 Fatty acids
 A fatty acid is a carboxylic acid with a long aliphatic chain, which is
either saturated or unsaturated. Most naturally occurring fatty acids
have an unbranched chain of an even number of carbon atoms, from 4
to 28. In a fatty acid chain, if there are only single bonds between
neighboring carbons in the hydrocarbon chain, the fatty acid is said to
be saturated. Stearic acid and palmitic acid (common in meat) and
butyric acid (common in butter) are examples of saturated fatty acids.

Fig. Stearic acid

 When the hydrocarbon chain contains a double bond, the fatty acid is
said to be unsaturated. Oleic acid is an example of an unsaturated
fatty acid. Unsaturated fatty acids are usually of plant origin and
contain double bonds cis configuration.

26
 Fats
 A fat molecule consists of two main components - glycerol and fatty
acids. Glycerol is an organic compound (alcohol) with three carbons,
five hydrogens, and three hydroxyl groups.
 Fatty acids have a long chain of hydrocarbons to which a carboxyl
group is attached, hence the name “fatty acid.”
 The number of carbons in the fatty acid may range from 4 to 36; most
common are those containing 12-18 carbons. In a fat molecule, the
fatty acids are attached to each of the three carbons of the glycerol
molecule with an ester bond through an O2 atom.
 During this ester bond formation, three water molecules are released.
The three fatty acids in the triacylglycerol may be similar or dissimilar.
Fats are also called triacylglycerols or triglycerides because of
their chemical structure.
 Some fatty acids have common names that specify their origin. For
example, palmitic acid, a saturated fatty acid, is derived from the
palm tree. Arachidic acid is derived from Arachis hypogea, the
scientific name for groundnuts or peanuts. 27
Figure: Triacylglycerol is formed by the joining of three fatty
acids to a glycerol backbone in a dehydration reaction. Three
28
molecules of water are released in the process.
 Fats and Oils
 Most unsaturated fats are liquid at room temperature and are
called oils. If there is one double bond in the molecule, then it
is known as a monounsaturated fat (e.g., olive oil), and if there
is more than one double bond, then it is known as a
polyunsaturated fat (e.g., canola oil).
 Cis and trans indicate the configuration of the molecule around
the double bond. If hydrogens are present in the same plane,
it is referred to as a cis fat; if the hydrogen atoms are on two
different planes, it is referred to as a trans fat.
 The cis double bond causes a bend or a “kink” that prevents
the fatty acids from packing tightly, keeping them liquid at
room temperature. Olive oil, corn oil, canola oil, and cod liver
oil are examples of unsaturated fats.
 Unsaturated fats help to lower blood cholesterol levels where-
as saturated fats contribute to plaque formation in the arteries.
29
Figure: Saturated fatty acids have hydrocarbon chains connected
by single bonds only. Unsaturated fatty acids have one or more
double bonds. Each double bond may be in a cis or trans
configuration. A cis double bond causes a kink in the chain. 30
 Trans Fats
 In the food industry, oils are artificially hydrogenated to make
them semi-solid and of a consistency desirable for many
processed food products.
 Simply speaking, hydrogen gas is bubbled through oils to
solidify them. During this hydrogenation process, double
bonds of the cis-conformation in the hydrocarbon chain may
be converted to double bonds in the trans-conformation.
 Margarine and some types of peanut butter are examples of
artificially hydrogenated trans fats. Recent studies have
shown that an increase in trans fats in the human diet may
lead to an increase in levels of low-density lipoproteins (LDL),
or “bad” cholesterol, which in turn may lead to plaque
deposition in the arteries, resulting in heart disease.
 Many fast food restaurants have recently banned the use of
trans fats, and food labels are required to display the trans
fat content. 31
 Omega Fatty Acids
 Essential fatty acids are fatty acids required but not
synthesized by the human body. Consequently, they have to
be supplemented through ingestion via the diet.
 Omega-3 fatty acids fall into this category and are one of only
two known for humans (the other being omega-6 fatty acid).
These are polyunsaturated fatty acids and are called omega-3
because the third carbon from the end of the hydrocarbon
chain is connected to its neighboring carbon by a double bond.
 The farthest carbon away from the
carboxyl group is numbered as the
omega (ω) carbon, and if the double
bond is between the 3rd and 4th carbon
from that end, it is known as an
omega-3 fatty acid. -linolenate is an -linolenic acid
example of an omega-3 fatty acid. It
has three cis double bonds and, as a
32
result, a curved shape.
Nutritional value of Omega fatty acids:
 Nutritionally important because the body does not make them,
omega-3 fatty acids include alpha-linolenic acid (ALA), eicosa-
pentaenoic acid (EPA), and docosa-hexaenoic acid (DHA), all
of which are polyunsaturated. Salmon, trout, and tuna are
good sources of omega-3 fatty acids.
 Research indicates that omega-3 fatty acids reduce the risk of
sudden death from heart attacks, reduce triglycerides in the
blood, lower blood pressure, and prevent thrombosis by
inhibiting blood clotting.
 They also reduce inflammation, and may help reduce the risk
of some cancers in animals.
 Waxes are made up of long fatty acid
chains esterified to long-chain alcohols.
What
 Wax coversis
thewax?
feathers of some aquatic birds
and the leaf surfaces of some plants. Because
of the hydrophobic nature of waxes, they 33
prevent water from sticking on the surface.
 Phospholipids
 Like fats, phospholipids are composed of fatty acid chains
attached to a glycerol or sphingosine backbone. They are
major constituents of the plasma membrane, the outermost
layer of animal cells.
 Unlike triglycerides, phospholipids contain two fatty acids
(diacylglycerol) where the third carbon of the glycerol
backbone is occupied by a modified phosphate group (the
phosphate group is modified by an alcohol).
 The precursor of phospholipids is phosphatidate (diacylgly-
cerol 3-phosphate). Phosphatidyl-choline and phosphatidyl-
serine are two important phospholipids that are found in
plasma membranes.
 A phospholipid is an amphipathic molecule having a hydro-
phobic and a hydrophilic part. The fatty acid chains are hydro-
phobic and cannot interact with water, whereas the phosphate
containing group is hydrophilic and interacts with water. 34
Phospholipid & Cell Membrane
 A phospholipid is a molecule with
two fatty acids and a modified
phosphate group attached to a
glycerol backbone.
 The phosphate can be modified by
choline and serine. Both choline
and serine attach to the
phosphate group at the position
labeled R.
 The phospholipid bilayer is the major
component of all cellular membranes.
 The hydrophilic head groups of the
phospholipids face the aqueous
solution.
 The hydrophobic tails are sequestered
35
in the middle of the bilayer.
 Steroids
 Unlike the phospholipids and fats discussed earlier, steroids
have a fused ring structure. Although they do not resemble the
other lipids, they are grouped with them because they are also
hydrophobic and insoluble in water.
 All steroids have four linked carbon rings and several of them,
like cholesterol, have a short tail.
 Many steroids also have the hydroxyl functional group, which
puts them in the alcohol classification (sterols).

Cholesterol Cortisol (sterol)

36
 Importance of Cholesterol
 Cholesterol is the most common steroid. Cholesterol is
mainly synthesized in the liver and is the precursor to many
steroid hormones such as testosterone and estradiol, which
are secreted by the gonads and endocrine glands.
 Cholesterol is also the precursor to Vitamin D. It is also the
precursor of bile salts, which help in the emulsification of
fats and their subsequent absorption by cells.
 Although cholesterol is often spoken of in negative terms by
lay people, it is necessary for proper body functioning.
 It is a component of the plasma membrane of animal cells
and is found within the phospholipid bilayer.
 Being the outermost structure in animal cells, the plasma
membrane is responsible for the transport of materials and
cellular recognition and communication. 37
 Macromolecule: Proteins
 Proteins are one of the most abundant organic molecules in
living systems and have the most diverse range of functions
of all macromolecules. They may be toxins or enzymes.
 Proteins have different shapes and molecular weights; some
proteins are globular in shape whereas others are fibrous in
nature. For example, hemoglobin is a globular protein, but
collagen, found in our skin, is a fibrous protein.
 Protein shape is critical to its function, and this shape is
maintained by many different types of chemical bonds.
 Changes in temperature, pH, and exposure to chemicals
may lead to permanent changes in the shape of the protein,
leading to loss of function, known as denaturation.
 All proteins are made up of different arrangements of the
same 20 types of amino acids. 38
Protein Types and Functions

39
 Amino Acids
 Amino acids are the monomers that make up proteins. Each
amino acid has the same fundamental structure, which
consists of a central carbon atom, also known as the alpha
(α) carbon, bonded to an amino group (NH2), a carboxyl
group (COOH), and to a hydrogen atom.
 Every amino acid also has another atom or group of atoms
bonded to the central atom known as the R group.
 The name "amino acid" is
derived from the fact that they
contain both amino group
and carboxyl-acid group.
 Amino acids have a central
asymmetric carbon to which
an NH2, a COOH, a H atom,
and a side chain (R group)
are attached. 40
 Classification of amino acids (contd.)
 The chemical nature of the side chain (R groups)
determines the nature of the amino acid. Based on
the R groups, amino acids can be classified as
Non-polar aliphatic (6) (glycine, alanine, valine,
leucine, methionine and isoleucine).
Polar uncharged (6) (serine, threonine,
cysteine, proline, asparagine and glutamine).
Positively charged (3) (lysine, arginine and
histidine).
Negatively charged (2) (aspartic acid and
glutamic acid).
Non-polar aromatic (3) (phenylalanine, tyrosine
and tryptophan). 41
 Structure of Amino Acids
 An amino acid usually contains both a negative
carboxylate and a positive α-ammonium group at pH
between 2.2 and 9.4, so has net zero charge.
 This molecular state is known as a zwitterion.

An amino acid in its un-ionized (1) and zwitterionic forms42(2).

43
44
45
 Acidic (- R)  Basic (+ R)

46
47
 Peptide bond and polypeptides
 The sequence and the number of amino acids ultimately
determine the protein's shape, size, and function.
 Each amino acid is attached to another amino acid by a
covalent bond, known as a peptide bond, which is formed
by a dehydration reaction.
 The carboxyl group of one amino acid and the amino group
of the incoming amino acid combine, releasing a molecule of
water. The resulting bond is the peptide bond.
 The products formed by such
linkages are called peptides. As
more amino acids join to this
growing chain, the resulting chain
is known as a polypeptide. Each
polypeptide has a free amino group
at one end and the other end has a
48
free carboxyl group
 Protein Structure
 While the terms polypeptide and protein are sometimes used
interchangeably, a polypeptide is technically a polymer of
amino acids, whereas the term protein is used for a
polypeptide or polypeptides that have combined together,
often have bound non-peptide prosthetic groups, have a
distinct shape, and have a unique function.
 After protein synthesis (translation), most proteins are
modified. These are known as post-translational modifications.
They may undergo cleavage, phosphorylation, or may require
the addition of other chemical groups. Only after these
modifications, protein becomes completely functional.
 The shape of a protein is critical to its function. To understand
how the protein gets its final shape or conformation, it is
necessary to understand the four levels of protein structure:
primary, secondary, tertiary, and quaternary. 49
50
 Primary Structure
 The unique sequence of amino acids in a polypeptide chain
is its primary structure. For example, the pancreatic
hormone insulin has two polypeptide chains (A and B) and
they are linked together by disulfide bonds.
 The N terminal amino acid of the chain A is glycine, whereas
the C terminal amino acid is asparagine. The sequences of
amino acids in the A and B chains are unique to insulin.

51
 Secondary Structure
 The local folding of the polypeptide in
some regions gives rise to the
secondary structure of the protein. The
most common are the α-helix and β-
pleated sheet structures.
 In α-helix, the hydrogen bonds form
between the oxygen atom in the carbonyl
group in one amino acid and amino
group in another amino acid that is four
amino acids farther along the chain.

52
 Secondary Structure (contd.)
 In the β-pleated sheet, the “pleats” are formed by hydrogen
bonding between atoms on the backbone of the polypeptide
chain. The R groups are attached to the carbons and extend
above and below the folds of the pleat.
 The pleated segments align parallel or
antiparallel to each other, and hydrogen
bonds form between the partially
positive hydrogen atom in the amino
group and the partially negative oxygen
atom in the carbonyl group of the
peptide backbone.
 The α-helix and β-pleated sheet
structures are found in most globular
and fibrous proteins and they play an
important structural role. 53
54
Difference between α-helix and β-pleated sheet

55
 Tertiary Structure
 The unique three-dimensional structure of a polypeptide is its
tertiary structure that refers to the spatial arrangement of amino
acid residues.
 The tertiary structure of proteins is determined by a variety of
chemical interactions between  helices and  pleated sheets.
 These interactions include hydrophobic interactions, ionic bonding,
hydrogen bonding and disulfide linkages.
 The nature of the R
groups found in the
amino acids involved can
counteract the formation
of the hydrogen bonds.
 For example, R groups
with like charges are
repelled by each other
and those with unlike
charges are attracted to
56
each other (ionic bonds).
 Quaternary Structure
 Proteins consisting of more than one polypeptide chain display
quaternary structure; each individual polypeptide chain is
called a subunit.
 Quaternary structure can be as simple as two identical sub-
units or as complex as dozens of different subunits.
 In most cases, the subunits are held together by non-covalent
bonds. Example, the 2-2 tetramer of human hemoglobin.
 The structure of the two
identical  subunits (red) is
similar to but not identical
with that of the two identical
 subunits (yellow). The
molecule contains four heme
groups (black with the iron
atom shown in purple). 57
 Denaturation and Protein Folding
 Each protein has its own unique sequence and shape that are
held together by chemical interactions. If the protein is subject
to changes in temperature, pH, or exposure to chemicals, the
protein structure may change, losing its shape without losing
its primary sequence in what is known as denaturation.
 Primary structure is unchanged by
denaturing.
 Denaturation is often reversible
because the primary structure of the
polypeptide is conserved in the
process if the denaturing agent is
removed, allowing the protein to
resume its function. 59
Denaturation and Protein Folding (contd.)
 Sometimes denaturation is irreversible, leading to loss of
function.
 One example of irreversible protein denaturation is when
an egg is fried. The albumin protein in the liquid egg white
is denatured when placed in a hot pan.
 Not all proteins are denatured at high temperatures; for
instance, bacteria that survive in hot springs have
proteins that function at temperatures close to boiling.
 Our stomach is also very acidic, has a low pH, and
denatures proteins as part of the digestion process;
however, the digestive enzymes (proteins) of the stomach
retain their activity under these harsh conditions. 60
 Nucleic Acids
 Nucleic acids are the most important macromolecules for
the continuity of life. The two main types of nucleic acids are
deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).
 DNA is the genetic material found in all living organisms,
ranging from single-celled bacteria to multi-cellular mammals.
 The entire genetic content of a cell is known as its
genome, and the study of genomes is genomics.
 In eukaryotic cells but not in prokaryotes, DNA forms a
complex with histone proteins to form chromatin, the
substance of eukaryotic chromosomes.
 A chromosome may contain tens of thousands of genes.
Many genes contain the information to make protein
products; other genes code for RNA products.
 DNA controls all of the cellular activities by turning the
genes “on” or “off.” 61
 Four major types of RNA
 The DNA molecules never leave the nucleus but instead use an
intermediary to communicate with the rest of the cell. This
intermediary is the messenger RNA (mRNA), which carries the
message from DNA.
 Other types such as ribosomal RNA (rRNA), transfer RNA
(tRNA), and microRNA (miRNA) are involved in protein
synthesis and its regulation. If a cell requires a certain protein to
be synthesized, the gene for this product is turned “on” and the
mRNA is synthesized in the nucleus.
 The base sequence of mRNA is complementary to the coding
sequence of the DNA from which it has been copied. In the
cytoplasm, the mRNA interacts with ribosomes and other
cellular machinery.
 rRNA is a major constituent of ribosomes on which the mRNA
binds. The rRNA ensures the proper alignment of the mRNA
62
and the ribosomes.
 Four major type of RNA (contd.)
 The rRNA of the ribosome also has an enzymatic activity
(peptidyl transferase) that catalyzes the formation of the
peptide bonds between two aligned amino acids.
 tRNA is one of the smallest of the four types of RNA, usually
70-90 nucleotides long. It carries the correct amino acid to
the site of protein synthesis.
 The base pairing between the tRNA and mRNA allows the
correct amino acid to be inserted in the polypeptide chain.
 microRNAs are the
smallest RNA molecules
and their role involves the
regulation of gene
expression by interfering
with the expression of
63
certain mRNA messages.
 Components of Nucleotide
 DNA and RNA are made up of monomers known as nucleotides.
The nucleotides combine with each other to form a polynucleotide,
DNA or RNA.
 Each nucleotide is made up of 3 components: a nitrogenous base, a
pentose (five-carbon) sugar, and a phosphate group.

64
 Components of Nucleotide (contd.)
 The nitrogenous bases, important components of
nucleotides, are organic molecules and are so named
because they contain carbon and nitrogen.
 Nucleotides are bases because they contain an amino group
that has the potential of binding an extra hydrogen, and thus,
decreases the hydrogen ion concentration in its environment,
making it more basic.
 Adenine (A) and guanine (G) are classified as purines. The
primary structure of a purine is two carbon-nitrogen rings.
Cytosine (C), thymine (T), and uracil (U) are classified as
pyrimidines which have a single carbon-nitrogen ring as
their primary structure.
 DNA contains A, T, G, and C whereas RNA contains A, U, G,
and C. The pentose sugar in DNA is deoxyribose, and in
RNA, the sugar is ribose. 65
 Components of Nucleotide (contd.)
 Each nitrogenous base is attached to
a sugar molecule, which is attached
to one or more phosphate groups.

66
 DNA Double-Helix Structure
 DNA has a double-helix structure. The sugar and phosphate lie
on the outside of the helix, forming the backbone.
 The two strands of the helix run in opposite directions, meaning
that the 5′ carbon end of one strand will face the 3′ carbon end
of the other strand.
 Only certain types of base pairing are allowed.
For example, a certain purine can only pair
with a certain pyrimidine. This means A can
pair with T, and G with C. This is known as the
base complementary rule.

67
 Major and Minor Grooves of DNA
 The minor groove occurs where the backbones are
close together. The major groove occurs where the
backbones are far apart.
 Every base
pair in the
double helix
is separated nm

from the
next base
pair by 0.34
nm.
 The nitrogenous bases are stacked in the interior, like the
steps of a staircase, in pairs; the pairs are bound to each
68
other by hydrogen bonds.
Mitochondrial DNA
Chloroplast DNA
 Differences between mitochondrial
and nuclear DNA
1. Nuclear DNA is found inside the nucleus of the cell while
mitochondrial DNA is found only in the mitochondria of the cell.
2. Nuclear DNA is linear in shape while mitochondrial DNA is
circular in shape.
3. Nuclear DNA is longer as compared to the mitochondrial DNA
which is shorter.
4. Nuclear DNA is inherited from the mother and father both
whereas on the other hand the mitochondrial DNA is inherited
from the mother only.
5. Nuclear DNA consists of forty six chromosomes while
mitochondrial DNA consists of only one chromosome.
6. The nuclear DNA contains 20,000 to 25,000 genes while
mitochondrial DNA contains only thirty seven genes.
7. The chromosomes in nuclear DNA are responsible genetic
make-up of a human being while the chromosome of the
mitochondrial DNA is responsible for the metabolic activities.71
 Central Dogma of Life
 As you have learned, information flow in an organism takes place
from DNA to RNA to protein. DNA dictates the structure of mRNA
in a process known as transcription, and RNA dictates the
structure of protein in a process known as translation.
 This is known as the Central Dogma of Life, which holds true for
all organisms. Exceptions to this rule occur in connection with
viral infections.
The following table summarizes the features of DNA and RNA.

72
Genetic Code Genetic Code

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