Molecules of Living Systems (Part-3)

MACROMOLECULES
Many biomolecules are macromolecules.

E.g., polysaccharides, proteins, and nucleic acids.

Relatively high molecular weight polymers.

Assembled from relatively simple precursors with molecular weights of

500 or less.

The number of polymerized units may range from tens to millions.

Macromolecular synthesis is a major energy-consuming activity of

cells.

Macromolecules may be further assembled into supramolecular

complexes, forming functional units such as ribosomes, which are
made of about 70 different proteins and 3-4 different RNA molecules.
CELLS ARE MOSTLY MADE OF MACROMOLECULES
Water is the most
abundant
compound in
virtually all cells and
organisms. Most of
the solid matter in
cells is organic that
occur in four forms:
proteins, nucleic
acids,
polysaccharides, and
lipids. A very small
fraction of the total
dry weight is
constituted by
inorganic salts and
mineral elements.
CELLS ARE MOSTLY MADE OF MACROMOLECULES
Proteins, polymers of amino acids, are the most versatile of all
biomolecules in terms of structure and function.

Some proteins, called enzymes have catalytic activity; others serve as

structural components, signal receptors, or transporters that carry
different substances, sometimes specifically, into or out of cells.

The nucleic acids, DNA and RNA, that store and transmit genetic
information, are polymers of nucleotides.

Some RNA molecules play structural and catalytic roles in RNA-protein

complexes.
CELLS ARE MOSTLY MADE OF MACROMOLECULES
Polysaccharides are polymers of simple sugar molecules such as
glucose.

Play two major roles: as energy-yielding fuel stores and as extracellular

structural elements.

The lipids are predominantly hydrophobic greasy or oily hydrocarbon

derivatives.

Serve as structural components of cellular and organelle membranes,

energy-rich fuel stores, pigments, and intracellular signals.
CELLS ARE MOSTLY MADE OF MACROMOLECULES

Most of these major cellular macromolecules (proteins, nucleotides

and polysaccharides) are synthesized in condensation reactions and
the number of monomeric subunits in the polymer can be enormous.

Proteins have molecular weights that may range from 5,000 to over 1
million; the molecular weights of nucleic acids can go up to several
billion; polysaccharides, such as starch, have molecular weights into
the millions.

Individual lipid molecules are relatively much smaller (Mr 750 to 1,500)
and are not macromolecules in true sense of the term. However,
millions of lipid molecules associate with noncovalent forces resulting
in the formation of very large structures such as cellular and organelle
membranes.
MONOMERIC SUBUNITS BUILD UP MACROMOLECULES
The structural composition of the large number of different proteins
and different nucleic acids are governed by a fundamental simplicity.

The simple monomeric units from which these macromolecules are

constructed are few in number and identical in all forms of life.

Each protein and each nucleic acid has a characteristic information-rich

subunit sequence, and hence they act as informational
macromolecules. The variety of
sequences that can
be made from the
four subunits of DNA
is limitless, as is the
number of melodies
possible with a few
musical notes.
MONOMERIC SUBUNITS BUILD UP MACROMOLECULES

Polysaccharides composed from a single kind of subunit, or two

different alternating units, do not carry much information.

Cellulose, a polymer of one

subunit type glucose (Glc) ,
is information-poor and
monotonous.

However, sugar oligomers, or oligosaccharides, made up of six or more

different kinds of sugars connected in branched chains have the
structural and stereochemical variety to carry information specifically
recognizable by other molecules and act as specific cellular signals.
STRUCTURES OF MONOMERIC SUBUNITS FOLLOW SIMPLE PATTERNS
Proteins are usually made of twenty different amino acids; all have an
amino group (an imino group in the case of proline), a carboxyl group
and a hydrogen atom attached to the same carbon atom, the α-carbon.
These α-amino acids differ from each other only in the fourth
substituent of the α-carbon, called the side chains (shaded pink).
STRUCTURES OF MONOMERIC SUBUNITS FOLLOW SIMPLE PATTERNS

Four kinds of nucleotides are the

structural units of DNA, and four
others are the units of RNA. Each
nucleotide consists of three
components: a nitrogenous
organic base and a five-carbon
sugar (together make a
nucleoside), to which is attached
a phosphate group.
Together, the eight different
nucleotides of DNA and RNA are
built from five different
nitrogenous organic bases and
two different five- carbon
sugars.
STRUCTURES OF MONOMERIC SUBUNITS FOLLOW SIMPLE PATTERNS

Lipids also are constructed from

relatively few types of compounds.
Most lipid molecules contain one or
more fatty acids of long, medium or
short chains, of which palmitic acid
and oleic acid are parent
compounds.
Many lipids also contain an alcohol,
such as glycerol, and some carry
phosphate.
STRUCTURES OF MONOMERIC SUBUNITS FOLLOW SIMPLE PATTERNS

Starch and cellulose, the most abundant polysaccharides in nature,

consist of repeating units of glucose.
Other polysaccharides are composed of different other sugar
molecules that are mostly derived from glucose.
STRUCTURES OF MONOMERIC SUBUNITS FOLLOW SIMPLE PATTERNS
Taken together, only three dozen organic compounds are the parents of
most of the different types of biomolecules:
CONDENSATION OF SUBUNITS INCREASES ORDER AND DEMANDS
ENERGY
The process of condensation of monomeric subunits to form
macrmolecules leads to increased order and decreased entropy in a
population of molecules with a positive free energy of formation and
hence contradicts the laws of thermodynamics.

Yet cells need these macromolecules which are less stable and more
highly ordered than a mixture of their monomeric components.

Since the processes are occurring in aqueous media, the loss in entropy
is more than compensated upon the synthesis and folding of the
macromolecule, by the release of a large number of water molecules
that remains non-covalently associated with the monomeric units.

To compensate for the free-energy deficit cells couple these

polymerization reactions to other reactions that liberate free energy,
so that the overall free energy change is negative.
CONDENSATION OF SUBUNITS INCREASES ORDER AND DEMANDS
ENERGY
As mentioned in the previous lecture, the usual source of free energy in
coupled biological reactions is obtained by hydrolysis of
phosphoanhydride bonds such as those in ATP:

When these reactions are coupled, the sum of ΔG1 and ΔG2 is
negative.

Using such strategies, cells synthesize and maintain the information-

rich polymers (DNA, RNA, and protein) that are absolutely essential to
life.
CELLULAR STRUCTURE FOLLOWS A HIERARCHIAL PATTERN
The monomeric units are much smaller in size than biological
macromolecules.

A molecule of the amino acid alanine is less than 0.5 nm long.

Hemoglobin, the oxygen-carrying protein of erythrocytes, consists of

about 600 amino acid molecules covalently linked into four long
chains, which are folded into globular shapes and associate non-
covalently to form a tetrameric structure with a diameter of 5.5 nm.

Individual protein molecules in turn are small compared with

supramolecular complexes such as ribosomes (about 20 nm in
diameter), which are in turn much smaller w.r.t. cellular organelles
such as mitochondria, about 1,000 nm in diameter, and can be
visualized under light microscope.
CELLULAR STRUCTURE FOLLOWS A HIERARCHIAL PATTERN
The general pattern of the structural hierarchy followed in the
molecular organization of cells:

A plant cell is shown, where the nucleus is an organelle containing several different kinds of
supramolecular complexes, such as chromosomes, which are complexes of DNA with many different
proteins. Each type of macromolecule is built from simple subunits— e.g., DNA from deoxyribonucleotides.
CELLULAR STRUCTURE FOLLOWS A HIERARCHIAL PATTERN

The monomeric subunits in proteins, nucleic acids, and

polysaccharides are joined by covalent bonds.

In supramolecular complexes, however, macromolecules associate with

each other by much weaker noncovalent interactions.

The major noncovalent forces are hydrogen bonds (between polar

groups), ionic interactions (between charged groups), hydrophobic
interactions (among nonpolar groups in aqueous solution), and van der
Waals interactions.

The large numbers of weak interactions between macromolecules in

supramolecular complexes exert significant stabilizing effect in these
noncovalent assemblies.
ORIGIN AND EVOLUTION OF MACROMOLECULES
The fact that all biological macromolecules in all life forms are made
from the same three dozen subunits strongly indicate that modern
organisms are descended from a single primordial cell line whose
fundamental chemistry remains recognizable to the present day.

Furthermore, several billion years of adaptive selection have fine-

tuned cellular systems to take maximum advantage of the
physicochemical properties of these molecular raw materials to carry
out the basic energy-transforming and self-replicating processes of a
living cell.
PREBIOTIC EVOLUTION: CHEMICAL EVOLUTION LED TO THE
FORMATION OF THE FIRST BIOMOLECULES
Organic compounds, including the basic biomolecules such as amino
acids and carbohydrates, occur in only trace amounts in the earth’s
crust, the sea, and the atmosphere.

This raises the question: how did the first living organisms acquire their
characteristic organic building blocks?

The biochemist Aleksandr I. Oparin proposed a theory, prebiotic

evolution, in 1922 for the origin of life early in the history of the earth,
postulating that the atmosphere at that time was very different from
that of today.

It was a reducing atmosphere, rich in methane, ammonia, and water,

and essentially devoid of oxygen, in contrast to the oxidizing
environment of our era.
PREBIOTIC EVOLUTION: CHEMICAL EVOLUTION LED TO THE
FORMATION OF THE FIRST BIOMOLECULES
According to this theory, electrical energy from lightning discharges or
heat energy from volcanoes led ammonia, methane, water vapor, and
some other components of the primitive atmosphere to react, resulting
in the formation of simple organic compounds.

Some of these compounds dissolved in the warm ancient seas, which

over time became enriched with a large variety of simple organic
substances.

In this “primordial soup”, some organic molecules had a greater

tendency than others to associate into larger complexes. Over millions
of years, these in turn assembled to form membrane-like structures
and catalysts (enzymes), which came together to give rise to
precursors of the earliest cells.
Oparin’s speculation was tested many years later, when a surprising
experiment was conducted using simple equipment on a desktop.
SIMULATION OF CHEMICAL EVOLUTION IN THE LABORATORY

Schematic of a spark-discharge
apparatus used by Miller and Urey
(1953) in experiments demonstrating
abiotic formation of organic
compounds under primitive
atmospheric conditions. The gaseous
contents of the system were subjected
to electrical sparks and products were
collected by condensation for a week
or more. A variety of organic
compounds, including some amino
acids, hydroxyl acids, aldehydes, and
hydrogen cyanide (HCN) were found in
the water phase. This experiment
established the possibility of abiotic
production of biomolecules.
SIMULATION OF CHEMICAL EVOLUTION IN THE LABORATORY
Modern extensions of the Miller experiments have demonstrated the
formation of hundreds of organic compounds:

In addition, polymers of nucleotides (nucleic acids) and of amino acids

(proteins) also form.
SIMULATION OF CHEMICAL EVOLUTION IN THE LABORATORY

The self-condensation products of HCN are efficient promoters of such

polymerization reactions, and inorganic ions present in the earth’s
crust (Cu2+, Ni2+, and Zn2+) further accelerate the rate of
polymerization.

The sources of energy that drive the formation of these compounds

include heat, visible and ultraviolet (UV) light, x rays, gamma radiation,
ultrasound and shock waves, and bombardment with α and β particles.

Short RNA polymers generated in such ways probably played a critical

role in prebiotic evolution, having the dual role of catalyst and
information repository.
THE FIRST GENES AND The discovery
CATALYSTS MIGHT that RNA
HAVE BEEN RNA molecules can
MOLECULES AND act as catalysts
RELATED PRECURSORS in their own
Lipid-like compounds in the formation
primordial soup formed suggests that
relatively impermeable layers
around self-replicating RNA or a similar
collections of molecules. The molecule may
concentration of proteins and have been the
nucleic acids within these lipid
enclosures favored the first gene
molecular interactions required (rather than
in self-replication. DNA) and the
Eventually, by developing their
own machineries to synthesize first catalyst
biomolecules, cells became (rather than
independent of the random protein) - the
processes by which such
compounds had first appeared “RNA world”
on Earth. hypothesis .