1
. oxidoreductases (oxidation-reduction),
2
. transferases (transfer of groups),
3. hydrolases (hydrolysis),
4. lyases (nonhydrolytic and nonoxidative cleavage of
groups),
5. isomerases (isomerization), and
6
. ligases or synthetases (joining of two molecules with
the breaking of a pyrophosphate bond).
The next two numbers in the code indicate the subgroup
and the sub-subgroup; the last number is the special serial
number given to each enzyme in its sub-subgroup.
Consider the systematic nomenclature for the enzyme
with the trivial name carbonic anhydrase, which facilitates
the transport of CO
2
by catalyzing the following reaction
(Chapter 1):
H
2
CO
3
(or H+ + HCO^) ^ H
2
O + CO
2
or
H2C03(or H+ -t-HC03“ )^ H 20 + C02
or
O
H + + HcP c'a T
H20 +
0
=
0 0
.
The systematic name for carbonic anhydrase is carbonate
hydro-lyase, and its numerical code is EC. 4.2.1.1. The first
number identifies it as a lyase; the second as an enzyme
that catalyzes the breakage of a carbon-oxygen bond, lead-
ing to unsaturated products; and the third as a hydro-lyase,
participating in a reaction involving the elimination of wa-
ter. The last number is the specific serial number assigned
to this enzyme. In this text, the trivial names are used.
Names of a selected list of clinically useful enzymes with
their EC codes, systematic names, other common names,
and abbreviations are given in Appendix V.
6.2 Catalysis
Specificity of Enzyme Catalysis
Enzymes are highly specific and usually catalyze only
one type of reaction. Some enzymes show absolute speci-
ficity. For example, pyruvate kinase catalyzes the trans-
fer of a phosphate group only from phosphoenolpyruvate
to adenosine diphosphate during glycolysis (Chapter 13).
Examples of enzymes that show less specificity are:
•
Hexokinase, which transfers the phosphate group
from adenosine triphosphate to several hexoses
86
of six classes on this basis of the type of reaction they
catalyze:
(D-glucose, 2-deoxy-D-glucose, D-fructose, and
D-mannose) at almost equivalent rates.
•
Phosphatase, which hydrolyzes phosphate groups
from a large variety of organic phosphate esters.
•
Esterase, which hydrolyzes esters to alcohols and
carboxylic acids, with considerable variation in
chain length in both the alkyl and acyl portions of
the ester.
•
Proteinase, which hydrolyzes peptide bonds
irrespective of the chemical nature of the substrate.
Many enzymes show stereoisomeric specificities. For
example, human a-amylase catalyzes the hydrolysis of
glucose from the linear portion of starch but not from
cellulose. Starch and cellulose are both polymers of glu-
cose, but in the former the sugar residues are connected
by
a(\ —*■
4) linkages, whereas in the latter they are con-
nected by >8(1 -* 4) linkages (Chapter 9).
Active Site and Enzyme-Substrate Complex
An enzyme-catalyzed reaction is initiated when the en-
zyme binds to its substrate to form an enzyme-substrate
complex. In general, enzyme molecules are considerably
larger than the substrate molecules. Exceptions are pro-
teinases, nucleases, and amylases that act on macromolec-
ular substrates. Irrespective of the size of the substrate,
binding to the enzyme occurs at a specific and special-
ized region known as the
active site,
a cleft or pocket in
the surface of the enzyme that constitutes only a small
portion of the enzyme molecule. Catalytic function is ac-
complished at this site because various chemical groups
important in substrate binding are brought together in a
spatial arrangement that confers specificity on the enzyme.
Thus, the unique catalytic property of an enzyme is based
on its three-dimensional structure and on an active site
whose chemical groups may be brought into close prox-
imity from different regions of the polypeptide chain. The
stereospecificity of an enzyme for a substrate has been
compared to a lock-and-key relationship. This analogy im-
plies that the enzyme has an active site that fits the exact
dimensions of the substrate (Figure 6-1). However, after
attachment of substrate, the enzyme may undergo confor-
mational changes that provide a more perfect fit between
it and the substrate. This process has been described as
induced fit
(Figure 6-2).
Factors Governing the Rate of
Enzyme-Catalyzed Reactions
The overall reaction involving conversion of substrate (S)
to product (P) with formation of the enzyme-substrate
chapter 6
Enzymes I: General Properties, Kinetics, and Inhibition
