Overview
• Enzymes are specialized proteins that function as catalysts to increase the
rate of biochemical reactions. By interacting with substrates (reactant
molecules upon which an enzyme acts), enzymes catalyze chemical
reactions involved in the biosynthesis of many cellular products. Enzymes
derive their name from Greek, in which the term enzyme means “in yeast”
and was mainly used to distinguish the whole microorganism, such as
yeast (“organized ferments”), from that of extracts of the whole
microorganisms (“unorganized ferments”). The implication was that
enzymes were unorganized ferments in yeast. Although the vast majority
of enzymes are proteins, certain nucleic acids (RNAs) also possess
enzymatic activity (i.e., ribozymes). Enzymes are the most efficient
catalysts known in nature, because they have the ability to increase
reaction rates by enormous factors. Like all catalysts, enzymes have the
ability to lower the activation energy of reactions, and the tremendous
catalytic power they possess results from their inherent ability to provide
stabilization to the reacting molecules at their activated complex states.
Classification
Enzymes have been classified on the type of reaction catalyzed, and six major classes
(families) of enzymes, numbered from 1 to 6, have been assigned by the Enzyme
Commission (EC) of the International Union of Biochemistry and Molecular Biology (7).
These classes are as follows: 1) oxidoreductases (e.g., dehydro-genases); 2)
transferases (group transfer enzymes; e.g.,kinases); 3) hydrolases (hydrolytic reactions;
e.g., ester-ases); 4) lyases (formation or removal of double bonds; e.g., hydratase—
addition of water across a double bond); 5) isomerases (e.g., mutarotation of glucose
by mutases); and 6) ligases (joining of two substrates at the expense of energy, also
referred to as synthetases). All discovered enzymes are identified by the prefix EC
followed by an Arabic numeral based on the major class of reaction catalyzed, as
indicated earlier. Furthermore, this is followed by a series of three more Arabic
numerals, which indicate the subclass (functionality), sub-sub class (specific bond
type), and serial number of the enzyme in that class, respectively. For example, the
enzyme acetylcholinesterase has been given the following assignment: EC 3.1.1.7. As
can been seen in this example, the numeral 3 indicates that this enzyme belongs to
the family of hydrolases, the first 1 indicates that the nature of the bond being
hydrolyzed is an ester, the second 1 indicates that specific ester bond is a carboxylic
acid ester, and the last number is the serial number of this enzyme in this subclass.
GENERAL CONCEPTS OF ENZYME INHIBITION
The body is composed of thousands of different enzymes, many of
them acting in concert to maintain homeostasis. Although disease
states may arise from the malfunc-tioning of a particular enzyme, or
the introduction of a foreign enzyme through infection by
microorganisms, inhibiting a specific enzyme to alleviate a disease
state is a challenging process. Most bodily functions occur through a
cascade of enzymatic systems, and it becomes extremely difficult to
design a drug molecule that can selectively inhibit an enzyme and
result in a therapeutic benefit. However, to address this problem, the
basic mechanism of enzyme action needs to be understood. Once
knowledge of a particular enzymatic pathway is determined and the
mechanism and kinetics are worked out, the challenge is then to
design a suitable inhibitor that is selectively used by the enzyme
causing its inhibition.
Competitive inhibition is a form of enzyme inhibition where binding of the inhibitor to the
active site on the enzyme prevents binding of the substrate and vice versa
Uncompetitive inhibition, also known as anti-competitive inhibition, takes place when an
enzyme inhibitor binds only to the complex formed between the enzyme and the substrate
(the E-S complex).
Non-competitive inhibition is a type of enzyme inhibition where the inhibitor reduces the
activity of the enzyme and binds equally well to the enzyme whether or not it has already
bound the substrate
Reversible Enzyme Inhibition
• Reversible inhibitors bind non-covalently and
different types of inhibition are produced
depending on whether these inhibitors bind to
the enzyme, the enzyme-substrate complex,
or both
Irreversible enzyme inhibition
• Irreversible inhibitors usually react with the
enzyme and change it chemically (e.g. via
covalent bond formation). These inhibitors
modify key amino acid residues needed for
enzymatic activity.
How to understand the type of inhibition: Enzyme kinetics
Irreversible inhibitor