Fundamentals of Medicinal Chemistry

Table A7.1 The classification of enzymes

Code Classification Type of reaction catalysed

1 Oxidoreductases Oxidations and reductions

2 Transferases The transfer of a group from one molecule to another

3 Hydrolases Hydrolysis of various functional groups

4 Lyases Cleavage of a bond by nonoxidative and

nonhydrolytic mechanisms

5 Isomerases The interconversion of all types of isomer

6 Ligases (synthases) The formation of a bond between molecules

given in the International Union of Biochemistry (IUB) publicationEnzyme

Nomenclature. This text uses trivial names, as they are usually easier to read in

print. In addition, some letter abbreviations are also used.

In its simplest form, the catalytic action of enzymes is believed to depend on

the substrate or substrates, binding to the surface of the enzyme. This binding

usually occurs on a specific part of the enzyme known as itsactive site. Once the

substrate (S) or substrates are bound to the surface of the enzyme (E) reaction

takes place and the products (P) are formed and released, whilst the enzyme is

recycled into the system.

E + S

Recycled

E−S complex E−P complex P + E

It is believed that an enzyme considerably reduces the activation energy

required for each of the stages in an enzyme controlled reaction (Figure A7.1).

Active sites are usually visualized as either pockets, clefts or indentations in

the surface of the enzyme. The amino acid residues forming the site can be

located some distance apart in the peptide chain but are brought together by the

folding of the peptide chain. The binding of a substrate to an active site is

believed to involve a mutual change in the conformations of both the substrate

and the enzyme. These changes allow the substrate to bind in the exact position

necessary for reaction, which explains why enzymes are more effective than

chemical catalysts in increasing the rates of reaction. The change in conform-

ation caused by a substrate binding to the active site can also result in the

formation of another active site, known as anallosteric site, on the enzyme. This

behaviour is known asallosteric activation. It occurs with increasing concen-

tration of the substrate and increases the capacity of the enzyme to process

substrate.

APPENDIX 7 ENZYMES 253