Enzymes WORLD OF MICROBIOLOGY AND IMMUNOLOGY192•
ily and efficiently able to bind. This effect is called induction.
Conversely, effectors can associate with the operator and alter
the configuration so that the binding of the polymerase occurs
less efficiently or not at all. This effect is known as repression.
Enzyme induction is a process where an enzyme is
manufactured in response to the presence of a specific mole-
cule. This molecule is termed an inducer. Typically, an inducer
molecule is a compound that the enzyme acts upon. In the
induction process, the inducer molecule combines with
another molecule, which is called the repressor. The binding of
the inducer to the repressor blocks the function of the repres-
sor, which is to bind to a specific region called an operator.
The operator is the site to which another molecule, known as
ribonucleic acid(RNA) polymerase, binds and begins the tran-
scriptionof the geneto produce the so-called messenger RNA
that acts as a template for the subsequent production of pro-
tein. Thus, the binding of the inducer to the repressor keeps the
repressor from preventing transcription, and so the gene cod-
ing for the inducible enzyme is transcribed. Repression of
transcription is essentially the default behavior, which is over-
ridden once the inducing molecule is present.
In bacteria, the lactose (lac) operonis a very well char-
acterized system that operates on the basis of induction.
Enzyme repression is when the repressor molecules pre-
vent the manufacture of an enzyme. Repression typically oper-
ates by feedback inhibition. For example, if the end product of
a series of enzyme-catalyzed reactions is a particular amino
acid, that amino acid acts as the repressor molecule to further
production. Often the repressor will combine with another
molecule and the duo is able to block the operation of the
operator. This blockage can occur when the repressor duo out-
competes with the polymerase for the binding site on the oper-
ator. Alternately, the repressor duo can bind directly to the
polymerase and, by stimulating a change in the shape of the
polymerase, prevent the subsequent binding to the operator
region. Either way, the result is the blockage of the transcrip-
tion of the particular gene.
The gene that is blocked in enzyme repression tends to
be the first enzyme in the pathway leading to the manufacture
of the repressor. Thus, repression acts to inhibit the production
of all the enzymes involved in the metabolic pathway. This
saves the bacterium energy. Otherwise, enzymes would be
made—at a high metabolic cost—for which there would be no
role in cellular processes.
Induction and repression mechanisms tend to cycle back
and forth in response to the level of effector, and in response
to nutrient concentration, pH, or other conditions for which the
particular effector is sensitive.See alsoMetabolism; Microbial geneticsEEnzymesNZYMES
Enzymes are molecules that act as critical catalysts in biolog-
ical systems. Catalysts are substances that increase the rate of
chemical reactions without being consumed in the reaction.
Without enzymes, many reactions would require higher levelsof energy and higher temperatures than exist in biological sys-
tems. Enzymes are proteins that possess specific binding sites
for other molecules (substrates). A series of weak binding
interactions allow enzymes to accelerate reaction rates.
Enzyme kinetics is the study of enzymatic reactions and
mechanisms. Enzyme inhibitor studies have allowed
researchers to develop therapies for the treatment of diseases,
including AIDS.
French chemist Louis Pasteur(1822–1895) was an
early investigator of enzyme action. Pasteur hypothesized that
the conversion of sugar into alcohol by yeastwas catalyzed by
“ferments,” which he thought could not be separated from liv-
ing cells. In 1897, German biochemist Eduard Buchner
(1860–1917) isolated the enzymes that catalyze the fermenta-
tionof alcohol from living yeast cells. In 1909, English physi-
cian Sir Archibald Garrod (1857–1936) first characterized
enzymes genetically through the one gene-one enzyme
hypothesis. Garrod studied the human disease alkaptonuria, a
hereditary disease characterized by the darkening of excreted
urine after exposure to air. He hypothesized that alkaptonurics
lack an enzyme that breaks down alkaptans to normal excre-
tion products, that alkaptonurics inherit this inability to pro-
duce a specific enzyme, and that they inherit a mutant form of
a genefrom each of their parents and have two mutant forms
of the same gene. Thus, he hypothesized, some genes contain
information to specify particular enzymes.
The early twentieth century saw dramatic advancement
in enzyme studies. German chemist Emil Fischer (1852–1919)
recognized the importance of substrate shape for binding by
enzymes. German-American biochemist Leonor Michaelis
(1875–1949) and Canadian biologist Maud Menten
(1879–1960) introduced a mathematical approach for quanti-
fying enzyme-catalyzed reactions. American chemists James
Sumner (1887–1955) and John Northrop (1891–1987) were
among the first to produce highly ordered enzyme crystals and
firmly establish the proteinaceous nature of these biological
catalysts. In 1937, German-born British biochemist Hans
Krebs(1900–1981) postulated how a series of enzymatic reac-
tions were coordinated in the citric acid cycle for the produc-
tion of ATP from glucose metabolites. Today, enzymology is a
central part of biochemical study, and the fields of industrial
microbiology and genetics employ enzymes in numerous
ways, from food production to gene cloning, to advanced ther-
apeutic techniques.
Enzymes are proteins that encompass a large range of
molecular size and mass. They may be composed of more than
one polypeptide chain. Each polypeptide chain is called a sub-
unit and may have a separate catalytic function. Some
enzymes require non-protein groups for enzymatic activity.
These components include metal ions and organic molecules
called coenzymes. Coenzymes that are tightly or covalently
attached to enzymes are termed prosthetic groups. Prosthetic
groups contain critical chemical groups which allow the over-
all catalytic event to occur.
Enzymes bind their substrates at special folds and clefts
in their structures called active sites. Because active sites have
chemical groups precisely located and orientated for binding
the substrate, they generally display a high degree of substratewomi_E 5/6/03 2:12 PM Page 192