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CHAPTER 2 The Structure and Functions of

Biological Molecules
COVALENT BONDS - Bonds between atoms with shared pairs of
electrons

governed by the principle that an atom is most stable when its


outermost electron shell is filled.

formation is accompanied by release of energy, which must be


reabsorbed at some later time if the bond is to be broken.

The energy required to cleave CH, CC, or CO covalent


bonds is between 80 and 100 (kcal/mol)1

bonds stable under most conditions.

Multiple bonds are formed when more than one pair of electrons
are shared by two atoms.

Shared electrons stay closest to the nucleus with the highest


electronegativity.
o
Depends upon the number of protons in nucleus.
o
Depends upon the distance of the shard electrons from the
nucleus.
Polar molecules have asymmetric distributions of electrical charge.
Nonpolar molecules lack polarized bonds.
Some biological molecules, such as proteins and phospholipids, have
both polar and nonpolar regions.
Ionization

Ions result when strongly electronegative nuclei capture


electrons.

Anions have extra electrons.

Cations have lost electrons.


FREE RADICALS are unstable atoms or molecules with unpaired
electrons.

They are formed during normal metabolism.

Are highly reactive and damage macromolecules such as DNA.

May play a role in aging.


Superoxide dismutase (SOD) is an enzyme that destroys the
superoxide radical (O2.).

protects cells from damage due to the superoxide radical.

extends the life span of laboratory animals that overproduce it.


Calorie restriction:

Extends the lifespan of experimental animals.

Results in decreased production of free radicals.

A new study indicates that individuals on a diet containing 25%


fewer calories show reduced levels of DNA damage.
NON-COVALENT BONDS are attractive forces that are weaker than
covalent bonds.

Weak bonds are broken and re-formed.

Weak bonds play an important role in dynamic cellular processes.


Types of non-covalent bonds
1. Ionic bonds attractions between charged atoms.

Are weakened in the presence of water.

They may be significant within large biological molecules.


2. Hydrogen bonds - occurs when covalently bound hydrogen has a
partial positive charge and attracts electrons of a second atom.

determine the structure and properties of water.

occur in biological molecules, such as between the strands of


DNA.
3. Hydrophobic interaction and van de Waals forces:

These occur when nonpolar molecules associate and


minimize their exposure to polar molecules/hydrophilic mol.

van der Waals forces, or attractions between nonpolar


molecules, are due to transient dipole formation.

Van der waals forces operate at optimum distances and are


maximized by complementary surfaces

The Life-Supporting Properties of Water


1. The structure of water is suitable for sustaining life.
i. It is asymmetric both H atoms are on one side.
ii. Both covalent OH bonds are highly polarized.
iii. All three atoms readily form H-bonds.
2.

The
i.
ii.
iii.

properties of water result from its structure.


It requires a lot heat to evaporate it.
It is an excellent solvent for many substances.
It determines the interactions between many biological
solutes.

H3O H+ + H2O OH + H+
Acid
Amphoteric Base
Acids release protons.
Bases accept protons.
Amphoteric molecules can act as either acids or bases. For example,
water:

Acidity is measure using the pH scale.

pH = log [H+]

The ion product constant for water is


Kw = [H+][OH] = 10-14 at 25 C.

As [H+] increases, [OH] decreases so that the product


equals 1014.

Biological processes are sensitive to pH.

Changes in pH affect the ion state and function of proteins.

Buffers in living systems resist changes in pH.

For example, bicarbonate ions and carbonic acid buffer the


blood:
HCO3 + H+ H2CO3

THE NATURE OF BIOLOGICAL MOLECULES


Carbon is central to the chemistry of life.

Carbon forms four covalent bonds, with itself or other


atoms.

Carbon-containing molecules produced by living organisms


are called biochemicals.
Hydrocarbons- Contain only carbon and hydrogen.

Vary in the number of carbons, and the number of double


and triple bonds between carbons.
Functional groupsgroups of atoms giving organic molecules
different characteristics and properties.
Functional classification of biological molecules:
Macromolecules: large structural and functional molecules in cells.
Include four major categories: proteins, nucleic acids, polysaccharides
and lipids.

Building blocks of macromolecules include amino acids,


nucleotides, sugars, and fatty acids.

Metabolic intermediates: compounds formed in


metabolic pathways.

Molecules of miscellaneous function: include vitamins,


hormones, ATP, and metabolic waste products.
FOUR TYPES OF BIOLOGICAL MOLECULES
1. CARBOHYDRATES include simple sugars and sugar polymers.

They serve as energy storage molecules.

Structure:

Chemical formula is (CH2O)n

Ketose sugars have a carbonyl (C=O) on an internal


carbon

Aldose sugars have a carbonyl on a terminal carbon.

Sugars can be linear but sometimes form ring structures.

Stereoisomerism:

Asymmetric carbons bond to four different groups.

Molecules with asymmetric carbons can exist in two


mirror-image configurations called enantiomers or
stereoisomers.

Enantiomers can be as either D- or L-isomers.

Sugars can have many asymmetric carbons, but are


designated D- or L- according to the arrangement around
the carbon farthest from the carbonyl group.

Linking Sugars Together:

Glycosidic bonds are COC links between sugars.

Disaccharides are used as a source of readily available


energy.

Oligosaccharides are found bound to cells surface


proteins and lipids, and may be used for cell recognition
Polysaccharides are polymers of sugars joined by glycosidic
bonds.

Glycogen is an animal product made of branched glucose


polymers.

Starch is a plant product made of both branched and


unbranched glucose polymers.
structural polysaccharides

Cellulose: plant product made of unbranched polymers

Chitin: component of invertebrate exoskeleton made

GAGs: composed of two different sugars and found in


extracellular space.

2. LIPIDS are a diverse group of nonpolar molecules.

Fats are made of glycerol linked by three ester bonds to three


fatty acids.

FAs are unbranched hydrocarbons with one carboxyl


group; they are amphipathic.
Saturated FAs lack C=C double bonds and are solid at
room temperature.
Unsaturated FAs have one or more C=C double bonds and
are liquid at room temperature.

Steroids are four-ringed animal lipids that have been


implicated in atherosclerosis.

Phospholipids are amphipathic lipids that are a major


component of cell membranes.
3. PROTEINS are polymers of amino acids and form a diverse group
of macromolecules.

They exhibit a high degree of specificity.

They have a variety of cellular functions.

The Building Blocks of Proteins

have an carbon, an amine group, a carboxyl group, and


a variable R group.

in nature occurs as the L stereoisomer.

are linked together by peptide bonds into a


polypeptide chain to make a protein.

Peptide bonds form between the -carbonyl and the -amino


of participating amino acids.

Amino acids differ in the R group attached to one of the


bonds of the -carbon.

R groups may be polar charged; polar uncharged;


nonpolar.
THE STRUCTURE OF PROTEINS

Primary structure, the sequence of amino acids in the


polymer, is critical to the protein function.

Secondary structure refers to the conformation of


adjacent amino acids into -helix, -sheet, hinges, turns,
turns, loops, or finger-like extensions.

Tertiary structure is the conformation of the entire


polymer.

It is stabilized by noncovalent bonds.

It is studied by X-ray crystallography.

Proteins can be fibrous or globular.

Myoglobin: The First Globular Proteins Whose Tertiary


Structure Was Determined
o
o
o

Stores oxygen in muscle cells.


Has a heme prosthetic group that binds O2.
Structure derived using X-ray crystallography.

Quaternary structure refers to proteins composed of


subunits.

It refers to the manner in which subunits interact.

A. Polar charged - contain R groups that act as stronger organic


acids, bases; can form ionic bonds

B. Polar uncharged - R groups weakly acidic or basic; not fully


charged at pH 7; can form H bonds with other molecules like water
since they have atoms with a partial negative or positive charge

C. Nonpolar - R groups hydrophobic; generally lack O & N; cannot


interact with water or form electrostatic bonds; vary primarily in size &
shape; allows them to pack tightly into protein core

D. The other three glycine, proline, cysteine


1. Glycine (R = H) - small R group makes backbone flexible & able to move
so it is useful in protein hinges; small R group allows 2 backbones (of same or
different protein) to approach closely
2. Proline R group forms ring with amino group (imino acid); hydrophobic
amino acid that does not readily fit into orderly secondary structure (a-helix)
3. Cysteine R group has reactive SH; forms disulfide (SS) bridge
with other cysteines often at some distance away in polypeptide backbone

R groups may have other properties.

The -carbon of proline is part of a ring, creating kinks

nature of the R groups determines the function of the protein.

Post-translational modifications

Phosphorylation of Tyr, Thr, Ser

Acetylation of Lys
Domains occur when proteins are composed of two or more
distinct regions. Each domain is a functional region
Conformational changes are non-random movements
triggered by the binding of a specific molecule.
Different proteins can become physically associated to form a
multiprotein complex.
Protein Folding is a process that occurs in various steps.

Anfinsen observed that unfolding is due to denaturation, brought


about by various agents.
Removal of denaturing agents could lead to refolding.

Two alternate pathways for protein folding:

Proteins may assume their native conformation through a series of steps.

Proteins may fold along pathways without intermediate forms.

Smaller proteins with single domains fold faster than larger proteins with
multiple domains.

PROTEIN MISFOLDING

Creutzfeld-Jakob Disease (CJD) results from misfolded


protein in the brain.

Healthy brains contain a normal protein, PrPc.


CJD brains have PrPSc, which is identical or similar to PrPc but is
misfolded.
Mad cow disease, kuru, and scrapie are also caused by PrPSc.

Alzheimers disease (AD) involves misfolded proteins that


accumulate in the brains of affected individuals.

A membrane-bound protein in brain neurons, called amyloid


precursor protein (APP), is cleaved by two secretase enzymes.
In individuals genetically predisposed to AD one of the cleavage
products is A42, a protein that misfolds and self-associates into
amyloid plaques.
All drugs for treatment of AD are aimed at management of
symptoms.
Pursuit of new drugs for AD aimed at:

Prevent formation of A42 peptide.

Remove the A42 peptide once it has formed.

Prevent interaction between A molecules.

Molecular chaperones are helper proteins to prevent nonselective


interactions during protein folding to achieve proper 3D conformation.

Hsp 70 family bind emerging proteins and prevent inappropriate


interactions.
Chaperonins allow large new proteins to assemble without interference
from other macromolecules. TriC processes up to 15% of the cells
proteins.

proteome is the entire inventory of an organisms proteins.


Proteomics uses advanced technologies to perform large-scale
studies on diverse proteins.

Proteins are separated using gel electrophoresis.


Proteins are identified using mass spectrometry and high speed computers.

Protein microarrays (protein chips) allow researchers to screen


proteins for various activities and disorders.
Site-directed mutagenesis allows researchers to make alterations
in single amino acids by altering the DNA encoding a protein.
Protein Adaptation and Evolution

Proteins are subject to natural selection.

Members of a protein family are thought to have evolved from a


single ancestor gene.

A particular protein may have different versions (isoforms) that


are tissue- or stage-specific.
4. NUCLEIC ACIDS are polymers of nucleotides that store and
transmit genetic information.

Nucleotides are connected by 3-5 phosphodiester bonds


between the phosphate of one nucleotide and the 3 carbon
of the next.

consists of three parts:


1. A five-carbon sugar
2. A phosphate group
3. A nitrogenous base

Bases are either purines or pyrimidines.


o
The purines are adenine and guanine in both DNA
and RNA.
o
The pyrimidines are cytosine and uracil in RNA;
uracil is replaced by thymine in DNA.

Deoxyribonucleic acid (DNA) holds the genetic


information in all cellular organisms and some viruses.

Ribonucleic acid (RNA) genetic material in some viruses

RNA is usually single stranded and DNA is usually


double stranded.

RNA may fold back on itself to form complex three


dimensional structures, as in ribosomes.
RNA may have catalytic activity; such RNA enzymes are
called ribozymes.
Adenosine triphosphate (ATP) is a nucleotide that
plays a key role in cellular metabolism, whereas
guanosine triphosphate (GTP) serves as a switch to
turn on some proteins.

The Formation of Complex Molecular Structure

Different types of subunits can self-assemble to form complex


structures.

One example is the tobacco mosaic virus (TMV), which was shown to
self-assemble from ribosomal subunits and proteins.

Cells may use molecular chaperones to assemble molecular


structures.

Some proteins can self-assemble from purified subunits.


Other proteins require molecular chaperones for proper
folding.

Molecular chaperones may protect protein structure


during the heat shock response.

The heat shock response involves synthesis of heat


shock proteins that prevent denaturation of existing
proteins.
Heat shock proteins and other chaperones prevent aggregation
of denatured or newly synthesized proteins.
Chaperones also move newly synthesized proteins across
membranes.

The protein GroEL is synthesized in E. coli is essential for the


proper folding of other cellular proteins.

GroEl acts in conjunction with another protein, GroES.

Attachment of GroES to GroEL induces a conformational change in the


GroEL protein.
The GroEL-GroES complex assists a protein and achieving its native state.
GroEl acts in conjunction with another protein, GroES.
Attachment of GroES to GroEL induces a conformational change in the
GroEL protein.

The GroEL-GroES complex assists a protein and achieving its native state.