Page 11 - Academic Press Encyclopedia of Physical Science and Technology 3rd Polymer

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Encyclopedia of Physical Science and Technology EN002C-64 May 19, 2001 20:39

Biopolymers 215

there are many hundreds of reactions occurring, each cat- magnetic resonance spectroscopy, it has been concluded
alyzed by a specific enzyme. that a protein has the same overall shape in solution as in
The way in which enzymes bring about such large in- the solid state, but that some minor changes can occur. For
creases in reaction rate is not understood completely, but enzymes it is known that a few amino acid side chains can
a number of factors probably contribute to the rate en- change position by several angstroms (10 −10 m) when the
hancement. An enzyme forms a temporary complex with substrate becomes bound to the enzyme molecule. Thus,
one or more of the reactants in a reaction. (The substances the active shape, or conformation, of an enzyme molecule
with which the enzyme interacts are called substrates for is not rigidly defined, but alterations can take place as the
the enzyme.) There is often strain on a substrate in such a enzyme carries out catalysis.
complex, allowing the substrate to react more readily than Many enzymes require the presence of ions or other
if the enzyme were absent. Immobilization of a substrate small molecules in order to show catalytic activity. These
on the surface of an enzyme can also allow a reaction to nonprotein components are called cofactors, and a small
occur more easily, particularly where a second reactant organic cofactor is usually known as a coenzyme. A coen-
is involved. The enzyme brings the two substrates into zyme may be covalently bound to an enzyme, in which
close proximity. Some amino acid side groups are capable case it would be classified as a prosthetic group of the
of donating and receiving protons (i.e., hydrogen ions), enzyme, or it may be loosely associated with the enzyme.
and if such groups on an enzyme are brought close to a Here the coenzyme often acts as a substrate for the en-
bond to be broken in a substrate, then bond breaking can zyme. Coenzymes are frequently derived from vitamins.
often occur more quickly. Some enzyme-catalyzed reac- Lack of such a vitamin in the human diet can result in
tions proceed via formation of an intermediate covalently an inactive enzyme or group of enzymes and can lead to
bonded to the enzyme; formation of such an intermediate development of a deficiency disease.
seems to speed up the overall reaction. In living tissues, the activities of many enzymes are reg-
Enzymes may act singly or may function as a group in a ulated by substances known as activators and inhibitors.
multienzyme complex. Usually each enzyme of a multien- These bind to enzymes and enhance or reduce the catalytic
zyme complex is responsible for catalyzing one step of a efficiency of the enzymes involved. Inhibitors can act sim-
complicated multistep biochemical pathway. Here greater ply by binding at the active site and preventing substrate
acceleration of reaction rate is possible if one enzyme binding. Certain lethal nerve gases, for example, modify
“passes on” the product of its reaction to the next enzyme the active site of an enzyme essential for the transmission
in the pathway. of nerve impulses; the result is paralysis and death. Where
Although enzyme molecules are large, the catalytic ac- the functioning of an enzyme is critical for the metabolism
tivity is usually associated with a relatively small area of of a disease-causing bacterium or virus, administration of
the molecular surface, where the substrate is bound and an enzyme inhibitor may be beneficial to an infected hu-
reaction takes place. This area is called the active site of man being. Thus inhibitors of an HIV enzyme necessary
the enzyme. When an enzyme possesses quaternary struc- for virus maturation are important anti-AIDS drugs.
ture (i.e., consists of several separate polypeptide chains) Many natural regulators of enzyme activity, however,
there may be more than one active site per molecule. The bind noncovalently at sites in the enzyme molecule other
active site is usually situated in a depression or a cleft than the active site. For these enzymes, then, parts of the
on the enzyme surface and is lined with amino acid side polypeptide chain(s) not involved in the active site have
groups that can bind the substrate—usually by weak bonds morethanastructuralrole;theyalsohavearegulatoryrole.
such as hydrogen bonds—and help to bring about the reac- It is believed that the activators and inhibitors bring about
tion being catalyzed. The active site is often formed from a change in the shape of the enzyme molecule and that
parts of the polypeptide chain, which are well separated in this shape change controls the efficiency of the active site.
primary structure, but brought together by the folding of Such enzymes are called allosteric enzymes, and many
the chain. One enzyme differs from another in the shape of consist of several noncovalently bonded peptide chains.
its active site and the nature of the side groups at the site. An inhibitor or activator may bind to one chain, while
In many enzymes, the remainder of the macromolecule the active site is located on another. In a case like this,
simply functions to maintain the shape and functionality the active site is affected by a change in quaternary struc-
of the active site. ture when the regulatory molecule is bound. Allosteric
The shapes of enzyme molecules, and proteins in gen- enzymes are believed to be capable of existing in inactive
eral, have been investigated by X-ray diffraction of protein and active states; binding of inhibitor favors the inactive
crystals(i.e.,thefoldingofpolypeptidechainsinsolidpro- state, while binding of activators favors the active state.
teins has been studied). From studies of smaller proteins The active and inactive states differ slightly in tertiary
of molecular weight 25,000 or less in solution by nuclear and/or quaternary structure.