Chapter: 3

The Structure and Function of Large

Biological Molecules

The Molecules of Life Macromolecules are polymers, built from monomers

The critically important large molecules of all living The macromolecules in three of the four classes of life's organic
things-from bacteria to elephants-fall into just four compounds-carbohydrates, proteins, and nucleic acids-are chain-like
main classes: carbohydrates, lipids, proteins, and molecules called polymers (from the Greek polys, many, and meros,
nucleic acids. On the molecular scale, members of part). A polymer is a long molecule consisting of many similar or
three of these classes-carbohydrates, proteins, and identical building blocks linked by covalent bonds. The repeating units
nucleic acids-are huge and are therefore called that serve as the building blocks of a polymer are smaller molecules
macromolecules. For example, a protein may consist called monomers (from the Greek monos, single).
of thousands of atoms that form a molecular colossus
with a mass well over 100,000 daltons.
The Synthesis and Breakdown of Polymers

Although each class of polymer is made up of a different type of

monomer, the chemical mechanisms by which cells make and
break down polymers are basically the same in all cases. In
cells, these processes are facilitated by enzymes, specialized
macromolecules that speed up chemical reactions.

Monomers are connected by a reaction in which two molecules

are covalently bonded to each other, with the loss of a water
molecule; this is known as a dehydration reaction (Figure
below). When a bond forms between two monomers, each
monomer contributes part of the water molecule that is released
during the reaction: One monomer provides a hydroxyl group (-
OH), while the other provides a hydrogen (-H). This reaction is
repeated as monomers are added to the chain one by one,
malting a polymer.
Polymers are disassembled to monomers by hydrolysis, a process The Diversity of Polymers
that is essentially the reverse of the dehydration reaction.
Each cell has thousands of different macromolecules; the
Hydrolysis means to break using water (from the Greek hydro,
collection varies from one type of cell to another even in the
water, and Lysis, break). The bond between the monomers is
same organism. The diversity of macromolecules in the living
broken by the addition of a water molecule, with the hydrogen
world is vast, and the possible variety is effectively limitless.
from the water attaching to one monomer and the hydroxyl group
attaching to the adjacent monomer.
Carbohydrates serve as fuel and building material

Carbohydrates include both sugars and polymers of sugars

(polysaccharides). The simplest carbohydrates are the
monosaccharides, or simple sugars; these are the monomers
from which more complex carbohydrates are constructed.
Disaccharides are double sugars, consisting of two
monosaccharides joined by a covalent bond.

Carbohydrates also include macromolecules called

polysaccharides, polymers composed of many sugar building
blocks.
Sugars

Monosaccharides (from the Greek monos, single, and sacchar, Depending on the location of the carbonyl group, a sugar is
sugar) generally have molecular formulas that are some multiple of either an aldose (aldehyde sugar) or a ketose (ketone sugar).
the unit CH2O. Glucose (C6H12O6), the most common Glucose, for example, is an aldose; fructose, an isomer of
monosaccharide, is of central importance in the chemistry of life. In glucose, is a ketose. (Most names for sugars end in -ose.)
the structure of glucose, fructose and galactose we can see the
trademarks of a sugar: The molecule has a carbonyl group (C=O) Another criterion for classifying sugars is the size of the carbon
and multiple hydroxyl groups (-OH). skeleton, which ranges from three to seven carbons long.
Glucose, fructose, and other sugars that have six carbons are
called hexoses. Trioses (three-carbon sugars) and pentoses
(five-carbon sugars) are also common.
Still another source of diversity for simple sugars is in the spatial arrangement of their
parts around asymmetric carbons. (Recall that an asymmetric carbon is a carbon
attached to four different atoms or groups of atoms.) Glucose and galactose, for
example, differ only in the placement of parts around one asymmetric carbon (see the
purple boxes in the Figure).

In aqueous solutions,
glucose molecules,
as well as most other
five- and six-carbon
sugars, form rings
(See the following
Figure).
A disaccharide consists of two monosaccharides joined
by a glycosidic linkage, a covalent bond formed between
two monosaccharides by a dehydration reaction. For
example, maltose is a disaccharide formed by the linking
of two molecules of glucose (See Figure below). Also
known as malt sugar, maltose is an ingredient used in
brewing beer. The most prevalent disaccharide is sucrose,
which is table sugar. Its two monomers are glucose and
fructose (See Figure below). Lactose, the sugar present in
milk, is another disaccharide, in this case a glucose
molecule joined to a galactose molecule.
Polysaccharides

Polysaccharides are macromolecules, polymers with a few hundred to a few

thousand monosaccharides joined by glycosidic linkages. Some
polysaccharides serve as storage material, hydrolyzed as needed to provide
sugar for cells. Other polysaccharides serve as building material for
structures that protect the cell or the whole organism.
Storage Polysaccharides

Both plants and animals store sugars for later use in the
form of storage polysaccharides.

Plants store a polysaccharide called starch, a polymer of

glucose monomers, as granules within cellular structures
known as plastids, which include chloroplasts.

Most of the glucose monomers in starch are joined by α1-4

linkages (number 1 carbon to number 4 carbon). The
simplest form of starch, amylose, is unbranched.
Amylopectin, a more complex starch, is a branched
polymer with α1-6 linkages at the branch points.

Animals store a polysaccharide called glycogen, a polymer of glucose joined by α1-4 linkages (number 1 carbon to number 4 carbon) that is
like amylopectin but more extensively branched. Humans and other vertebrates store glycogen mainly in liver and muscle cells. Hydrolysis of
glycogen in these cells releases glucose when the demand for sugar increases.
There are actually two slightly different ring structures for glucose (See Figure below). When glucose forms a ring, the hydroxyl group
attached to the number 1 carbon is positioned either below or above the plane of the ring. These two ring forms for glucose are called alpha
(α) and beta (β p), respectively. In starch, all the glucose monomers are in the α configuration.

Structural Polysaccharides

Organisms build strong materials from structural polysaccharides. For example, the polysaccharide called cellulose is a major component of
the tough walls that enclose plant cells (cell wall).

Like starch, cellulose is a polymer of glucose, but β glucose and the glycosidic linkages in these two polymers differ.
Whereas certain starch molecules are largely helical, a cellulose molecule is straight. Cellulose is never branched, and some hydroxyl
groups on its glucose monomers are free to hydrogen-bond with the hydroxyls of other cellulose molecules lying parallel to it. In plant
cell walls, parallel cellulose molecules held together in this way are grouped into units called microfibrils. These cable-like microfibrils
are a strong building material for plants and an important substance for humans because cellulose is the major constituent of paper and
the only component of cotton.
Enzymes that digest starch by hydrolyzing its a linkages are unable to hydrolyze the β linkages of cellulose because of the distinctly different
shapes of these two molecules. In fact, few organisms possess enzymes that can digest cellulose. Animals, including humans, do not; the
cellulose in our food passes through the digestive tract and is eliminated with the feces. Along the way, the cellulose abrades the wall of the
digestive tract and stimulates the lining to secrete mucus, which aids in the smooth passage of food through the tract.

Another important structural polysaccharide is chitin, the

carbohydrate used by arthropods (insects, spiders,
crustaceans, and related animals) to build their
exoskeletons. An exoskeleton is a hard case that surrounds
the soft parts of an animal. Pure chitin is leathery and
flexible, but it becomes hardened when encrusted with
calcium carbonate, a salt. Chitin is also found in many
fungi, which use this polysaccharide rather than cellulose
as the building material for their cell walls. Chitin is
similar to cellulose, a polymer of β glucose with β
linkages, except that the glucose monomer (N-
Acetylglucosamine) of chitin has a nitrogen-containing
appendage (See Figure below).
Lipids are a diverse group of hydrophobic molecules Fats
Although fats are not polymers, they are large molecules assembled from
Lipids are heterogeneous group of chemicals and the
smaller molecules by dehydration reactions. A fat is constructed from two
one class of large biological molecules that does not
kinds of smaller molecules: glycerol and fatty acids.
include true polymers, and they are generally not big
enough to be considered macromolecules. The Glycerol is an alcohol; each of its three carbons bears a hydroxyl group.
compounds called lipids are grouped together because
A fatty acid has a long carbon skeleton, usually 16 or 18 carbon atoms in
they share one important trait: They mix poorly, if at all,
length. The carbon at one end of the skeleton is part of a carboxyl group, the
with water.
functional group that gives these molecules the name fatty acid. The rest of the
The hydrophobic behavior of lipids is based on their skeleton consists of a hydrocarbon chain. The relatively nonpolar C-H bonds
molecular structure. Although they may have some in the hydrocarbon chains of fatty acids are the reason fats are hydrophobic.
polar bonds associated with oxygen, lipids consist
mostly of hydrocarbon regions. Lipids are varied in
form and function. They include waxes and certain
pigments, but we will focus on the most biologically
important types of lipids: fats, phospholipids, and
steroids.
Glycerol
In making a fat, three fatty add molecules are each joined to glycerol The terms saturated fats and unsaturated fats are commonly used
by an ester linkage, a bond between a hydroxyl group and a carboxyl in the context of nutrition. These terms refer to the structure of
group. The resulting fat, also called a triacylglycerol, thus consists of the hydrocarbon chains of the fatty acids. If there are no double
three fatty acids linked to one glycerol molecule. The fatty acids in a bonds between carbon atoms composing a chain, then as many
fat can be the same, or they can be of two or three different kinds, as in hydrogen atoms as possible are bonded to the carbon skeleton.
the Figure below. Such a structure is said to be saturated with hydrogen, and the
resulting fatty acid therefore called a saturated fatty add (See
next Figure).

An unsaturated fatty acid has one or more double bonds, with

one fewer hydrogen atom on each double-bonded carbon. Nearly
all double bonds in naturally occurring fatty acids are cis double
bonds, which cause a kink in the hydrocarbon chain wherever
they occur (See next Figure). A fat made from saturated fatty
acids is called a saturated fat. Most animal fats are saturated:
The hydrocarbon chains of their fatty acids-the "tails" of the fat
molecules-Jack double bonds, and their flexibility allows the fat
molecules to pack together tightly.
 A diet rich in saturated fats is one of several factors that may contribute to
the cardiovascular disease known as atherosclerosis. In this condition,
deposits called plaques develop within the walls of blood vessels, causing
inward bulges that impede blood flow and reduce the resilience of the
vessels.

Recent studies have shown that the process of hydrogenating vegetable oils
produces not only saturated fats but also unsaturated fats with trans
double bonds. These trans fats may contribute more than saturated fats to
atherosclerosis and other problems.

In contrast, the fats of plants and fishes are generally Certain unsaturated fatty acids must be supplied in the human diet because
unsaturated, meaning that they are built of one or more they cannot be synthesized in the body. These essential fatty acids include
types of unsaturated fatty acids. Usually liquid at room the omega-3 fatty acids, which are required for normal growth in children
temperature, plant and fish fats are referred to as oils. and appear to protect against cardiovascular disease in adults. Fatty fish
The kinks where the cis double bonds are located and certain nuts and vegetable oils are rich in omega-3 fatty acids (so
prevent the molecules from packing together closely named because they have a double bond at the third carbon-carbon bond
enough to solidify at room temperature. from the end of the hydrocarbon chain).
The major function of fats is energy storage. The hydrocarbon chains of Phospholipids
fats are similar to gasoline molecules and just as rich in energy. A gram Cells could not exist without another type of lipid-
of fat stores more than twice as much energy as a gram of a phospholipids (See Figure). Phospholipids are essential for
polysaccharide, such as starch. Because plants are relatively immobile, cells because they make up cell membranes. As shown in the
they can function with bulky energy storage in the form of starch. following Figure, a phospholipid is similar to a fat molecule
but has only two fatty acids attached to glycerol rather than
three. The third hydroxyl group of glycerol is joined to a
phosphate group, which has a negative electrical charge in the
cell. Additional small molecules, which are usually charged or
polar, can be linked to the phosphate group to form a variety of
phospholipids.
 When phospholipids are added to water, they self assemble into double-
layered structures called "bilayers," shielding their hydrophobic portions
from water (See Figure below).

At the surface of a cell, phospholipids are arranged in a similar bilayer.

The hydrophilic heads of the molecules are on the outside of the bilayer,
The two ends of phospholipids show different behavior
in contact with the aqueous solutions inside and outside of the cell. The
toward water. The hydrocarbon tails are hydrophobic and
hydrophobic tails point toward the interior of the bilayer, away from the
are excluded from water. However, the phosphate group and
water. The phospholipid bilayer forms a boundary between the cell and
its attachments form a hydrophilic head that has an affinity
its external environment; in fact, cells could not exist without
for water.
phospholipids.
Steroids Proteins
Steroids are lipids characterized by a carbon skeleton consisting of
four fused rings. Different steroids, such as cholesterol and the Nearly every dynamic function of a living being depends on

vertebrate sex hormones, are distinguished by the particular proteins. In fact, the importance of proteins is underscored by

chemical groups attached to this ensemble of rings (See next Figure). their name, which comes from the Greek word proteios,

Cholesterol is a crucial molecule in animals. It is a common meaning "first," or "primary." Proteins account for more than

component of animal cell membranes and is also the precursor from 50% of the dry mass of most cells, and they are instrumental in

which other steroids are synthesized. In vertebrates, cholesterol is almost everything organisms do.

synthesized in the liver and obtained from the diet. A high level of
Some proteins speed up chemical reactions, while others play a
cholesterol in the blood may contribute to atherosclerosis. In fact,
role in defense, storage, transport, cellular communication,
both saturated fats and trans fats exert their negative impact on
movement, or structural support. Figure below shows examples
health by affecting cholesterol levels.
of proteins with these functions.
A human has tens of thousands of different Amino Acid Monomers

proteins, each with a specific structure and

All amino acids share a common structure. An amino acid is an organic molecule
function; proteins, in fact, are the most
possessing both an amino group and a carboxyl group (see Figure below). The
structurally sophisticated molecules known.
illustration shows the general formula for an amino acid. At the center of the amino
Consistent with their diverse functions, they
acid is an asymmetric carbon atom called the alpha (α) carbon. Its four different
vary extensively in structure, each type of
partners are an amino group, a carboxyl group, a hydrogen atom, and a variable group
protein having a unique three-dimensional
symbolized by R. The R group, also called the side chain, differs with each amino acid.
shape.

Polypeptides
All proteins are unbranched polymers
constructed from the same set of 20 amino
acids. Polymers of amino acids are called
polypeptides. A protein is a biologically
functional molecule that consists of one or
The next Figure shows the 20 amino acids that cells use to build their thousands of
more polypeptides, each folded and coiled
proteins. Here the amino groups and carboxyl groups are all depicted in ionized form,
into a specific three dimensional structure.
the way they usually exist at the pH found in a cell.
The side chain (R group) may be as simple as a hydrogen atom, as in
the amino acid glycine, or it may be a carbon skeleton with various
functional groups attached, as in glutamine. The physical and
chemical properties of the side chain determine the unique
characteristics of a particular amino acid, thus affecting its
functional role in a polypeptide.

In the next Figure, the amino acids are grouped according to the
properties of their side chains. One group consists of amino acids
with nonpolar side chains, which are hydrophobic. Another group
consists of amino acids with polar side chains, which are
hydrophilic. Acidic amino acids are those with side chains that are
generally negative in charge owing to the presence of a carboxyl
group, which is usually dissociated (ionized) at cellular pH. Basic
amino acids have amino groups in their side chains that are generally
positive in charge. (Notice that all amino acids have carboxyl groups
and amino groups; the terms acidic and basic in this context refer
only to groups on the side chains.) Because they are charged, acidic
and basic side chains are also hydrophilic.
Amino Acid Polymers

When two amino acids are positioned so that the carboxyl group
of one is adjacent to the amino group of the other, they can
become joined by a dehydration reaction, with the removal of a
water molecule. The resulting covalent bond is called a peptide
bond. Repeated over and over, this process yields a
polypeptide, a polymer of many amino acids linked by peptide
bonds.

The repeating sequence of atoms highlighted in purple in next

Figure is called the polypeptide backbone. Extending from this
backbone are the different side chains (R groups) of the amino
acids. Each specific polypeptide has a unique linear sequence
of amino acids. Note that one end of the polypeptide chain has a
free amino group, while the opposite end has a free carboxyl
group. Thus, a polypeptide of any length has a single amino end
(N-terminus) and a single carboxyl end (C-terminus).
Protein Structure and Function

- The specific activities of proteins result from their

intricate three-dimensional architecture. The amino
acid sequence of each polypeptide determines what
three-dimensional structure the protein will have under
normal cellular conditions. When a cell synthesizes a
polypeptide, the chain generally folds spontaneously,
assuming the functional structure for that protein. This
folding is driven and reinforced by the formation of a
variety of bonds between parts of the chain, which in
turn depends on the sequence of amino acids.

- Many proteins are roughly spherical (globular

proteins), while others are shaped like long fibers
(fibrous proteins). Even within these broad
categories, countless variations exist.
Four Levels of Protein Structure

- In spite of their great diversity, all proteins

share three superimposed levels of structure,
known as primary, secondary, and tertiary
structure. A fourth level, quaternary structure,
arises when a protein consists of two or more
polypeptide chains.

- The simplest level of protein

structure, primary structure, is simply the
sequence of amino acids in a polypeptide
chain that linked by peptide bonds.
- Secondary structure, refers to local folded - Many proteins are made up of a single polypeptide chain
structures that form within a polypeptide due to and have only three levels of structure. However, some
interactions between the carbonyl O of one amino proteins are made up of multiple polypeptide chains, also
acid and the amino H of another. The most known as subunits. When these subunits come together,
common types of secondary structures are the α they give the protein its quaternary structure. In general,
helix and the β pleated sheet. Both structures are the same types of interactions that contribute to tertiary
held in shape by hydrogen bonds. structure which are hydrogen bonding, ionic bonding,
hydrophobic interactions and disulfide bond.
- Tertiary structure, refers to the overall three-
dimensional structure of a polypeptide. The tertiary
structure is primarily due to interactions between
the R groups of the amino acids that make up the
protein. R group interactions that contribute to
tertiary structure include hydrogen bonding,
ionic bonding, hydrophobic interactions and
disulfide bond.
Sickle-Cell Disease: A Change in Primary Structure

- Even a slight change in primary structure can affect a

protein's shape and ability to function. For instance,
sickle-cell disease, an inherited blood disorder, is caused
by the substitution of one amino acid (valine) for the
normal one (glutamic acid) at a particular position in the
primary structure of hemoglobin, the protein that carries
oxygen in red blood cells. Normal red blood cells are disk-
shaped, but in sickle-cell disease, the abnormal
hemoglobin molecules tend to crystallize, deforming some
of the cells into a sickle shape. A person with the disease
has periodic "sickle-cell crises" when the angular cells clog
tiny blood vessels, impeding blood flow.
What Determines Protein Structure?

- A polypeptide chain of a given amino acid sequence can - Because it is misshapen, the denatured protein is
spontaneously arrange itself into a three-dimensional biologically inactive. When the denaturing agent is
shape determined and maintained by the interactions removed proteins can sometimes return to its functional
responsible for secondary and tertiary structure. This shape in a process called renaturation (See Figure
folding normally occurs as the protein is being below).
synthesized in the crowded environment within a cell,
aided by other proteins. However, protein structure also
depends on the physical and chemical conditions of the
protein's environment. If the pH, salt concentration,
temperature, or other aspects of its environment are
altered, the weak chemical bonds and interactions within
a protein may be destroyed, causing the protein to
unravel and lose its native shape, a change called
denaturation.
Protein Folding in the Cell

- Protein-folding process is not that simple. Most

proteins probably go through several
intermediate structures on their way to a stable
shape, and looking at the mature structure does
not reveal the stages of folding required to
achieve that form.

- Crucial to the folding process are chaperonins

(also called chaperone proteins), protein
molecules that assist in the proper folding of
other proteins. Chaperonins do not specify the
final structure of a polypeptide. Instead, they
keep the new polypeptide segregated from "bad
influences" in the cytoplasmic environment while
it folds spontaneously.
Nucleic acids store, transmit, and help express hereditary
information

- If the primary structure of polypeptides (amino acids sequence) - DNA is the genetic material that organisms
determines a protein's shape, what determines primary structure? inherit from their parents. Each
The amino acid sequence of a polypeptide is programmed by a chromosome contains one long DNA
discrete unit of inheritance known as a gene. Genes consist of DNA, molecule, usually carrying several hundred
which belongs to the class of compounds called nucleic acids. or more genes. When a cell reproduces
Nucleic acids are polymers made of monomers called nucleotides. itself by dividing, its DNA molecules are
copied and passed along from one
The Roles of Nucleic Acids
generation of cells to the next. Encoded in
the structure of DNA is the information that
- The two types of nucleic acids, deoxyribonucleic acid (DNA) and
programs all the cell's activities. The DNA,
ribonucleic acid (RNA), enable living organisms to reproduce their
however, is not directly involved in running
complex components from one generation to the next. Unique
the operations of the cell, but actually,
among molecules, DNA provides directions for its own replication.
proteins are required to implement genetic
DNA also directs RNA synthesis and, through RNA, controls protein
programs.
synthesis.
- Each gene along a DNA molecule directs synthesis of a
type of RNA called messenger RNA (mRNA). The mRNA
molecule interacts with the cell's protein-synthesizing
machinery to direct production of a polypeptide, which folds
into all or part of a protein. We can summarize the flow of
genetic information as DNA RNA protein.

- The sites of protein synthesis are tiny structures called

ribosomes. In a eukaryotic cell, ribosomes are in the
cytoplasm, but DNA resides in the nucleus. Messenger RNA
conveys genetic instructions for building proteins from the
nucleus to the cytoplasm. Prokaryotic cells lack nuclei but
still use mRNA to convey a message from the DNA to
ribosomes and other cellular equipment that translate the
coded information into amino acid sequences.
The Components of Nucleic Acids

- Nucleic acids are macromolecules that

exist as polymers called
polynucleotides (Figure a). As
indicated by the name, each
polynucleotide consists of monomers
called nucleotides. A nucleotide, in
general, is composed of three parts: a
nitrogen containing (nitrogenous)
base, a five-carbon sugar (a
pentose), and one or more
phosphate groups (Figure b). In a
polynucleotide, each monomer has
only one phosphate group. The portion
of a nucleotide without any phosphate
groups is called a nucleoside.
- Each nitrogenous base has one or two - In DNA the sugar is deoxyribose; in RNA it is ribose. The only
rings that include nitrogen atoms. (They difference between these two sugars is that deoxyribose lacks an
are called nitrogenous bases because the oxygen atom on the second carbon in the ring; hence the name
nitrogen atoms tend to take up H+ from deoxyribose.
solution, thus acting as bases.) There are
two families of nitrogenous bases:
pyrimidines and purines. The members
of the pyrimidine family are cytosine (C),
thymine (T), and uracil (U). The purines
are adenine (A) and guanine (G).

- Adenine, guanine, and cytosine are found

in both DNA and RNA; thymine is found
only in DNA and uracil only in RNA.
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. This bonding results in a backbone with
a repeating pattern of sugar-phosphate units.
- The two free ends of the polymer are distinctly different The Structures of DNA and RNA
from each other. One end has a phosphate attached to Molecules
a 5' carbon, and the other end has a hydroxyl group on
a 3' carbon; we refer to these as the 5' end and the 3' - RNA molecules usually exist as single
end, respectively. polynucleotide chains like the one
shown in the Figure below. In contrast,
- We can say that a polynucleotide has a built-in DNA molecules have two polynudeotides,
directionality along its sugar-phosphate backbone, or "strands," that spiral around an
from S' to 3', somewhat like a one-way street. All along imaginary axis, forming a double helix
this sugar-phosphate backbone are appendages (See Figure below).
consisting of the nitrogenous bases.
The two sugar-phosphate backbones run in - The two strands are held together by hydrogen
opposite 5' 3' directions from each other; this bonds between the paired bases (see Figure
arrangement is referred to as antiparallel (See below). Only certain bases in the double helix are
Figure below), somewhat like a divided highway. compatible with each other. Adenine (A) always
The sugar phosphate backbones are on the outside pairs with thymine (T) by 2 hydrogen bonds, and
of the helix, and the nitrogenous bases are paired in guanine (G) always pairs with cytosine (C) by 3
the interior of the helix. hydrogen bonds.
- If we were to read the sequence of bases along one
strand of the double helix, we would know the
sequence of bases along the other strand. If a stretch
of one strand has the base sequence 5'-AGGTCCG-3',
then the base-pairing rules tell us that the same stretch
of the other strand must have the sequence 3'-
TCCAGGC-5'. The two strands of the double helix are
complementary, each the predictable counterpart of
the other.