section 6.2
Catalysis
87
F IG U R E 6-1
Schematic diagram of a lock and key relationship between an enzyme and
its substrate. The shape of the active site is complementary to that of the
substrate molecule.
complex, ES can be written:
ki
k'i
E + S ^ E S ^ E + P,
k
-i
k_2
where
k\, k
i,
k2,
and
k_2
are rate constants for the
designated steps; the positive subscripts indicate for-
ward reactions, and the negative subscripts indicate back-
ward reactions. Because an enzyme increases the rate
of a particular reaction by decreasing the free energy
of activation without itself being consumed or perma-
nently altered, a small number of enzyme molecules
can convert an extremely large number of substrate
molecules to products very rapidly. Enzymes do not al-
ter the equilibrium constant of a chemical reaction be-
cause they catalyze the forward and backward reactions
F IG U R E 6 -2
Schematic diagram of the induced-fit model for the relationship between
an enzyme and its substrate. The shape of the active site of the enzyme
conforms to that of the substrate
o n ly
after substrate binding induces
appropriate conformational changes in the enzyme.
to the same extent. Thus, enzymes affect only the
rate
at
which equilibrium is established between reactants and
products. However, under steady-state conditions, which
is the normal state of affairs in the human body,
the net effect of the enzyme is to convert substrates
to products as rapidly as the products are removed
(Chapter 5).
Effect o f Temperature
The rates of almost all chemical reactions increase with
a rise in temperature, which causes both the average ki-
netic energy and the average velocity of the molecules to
increase, resulting in a higher probability of effective reac-
tion collisions. Enzymes, however, undergo denaturation
and are inactivated at high temperatures. Below the denat-
uration temperature, the reaction rate will approximately
double for every rise of 10°C. The ratio by which the rate
changes for a 10°C increase in temperature is known as
<2io; this ratio varies from 1.7 to 2.5. The optimal temper-
ature for most enzymes is close to the normal temperature
of the organism at which catalysis occurs at the maximum
rate. In humans, most enzymes have an optimal tempera-
ture of 37°C.
Effect o f pH
The activity of most enzymes depends on pH. The pH-
enzyme activity profile of most enzymes delineates a bell-
shaped curve (Figure 6-3), exhibiting an optimal pH at
which activity is maximal. This pH is usually the same as
the pH of the fluid in which the enzyme functions. Thus,
most enzymes have their highest activity between pH
6
and pH
8
(the pH of human blood is about 7.4). However,
pepsin, which must function at the low pH of gastric juice,
has maximal activity at about pH 2.
The pH dependence of enzyme activity is the result
of several effects. Ionizable groups in the active site of
the enzyme (or elsewhere), in the substrate, or in the
enzyme-substrate complex can affect catalysis depend-
ing on whether the protons on the reactive groups are
dissociated or undissociated. Ionization of these groups
depends on their pK values, the chemical properties of
surrounding groups, and the pH of the reaction medium.
Changes in pH affect the binding of the substrate at the
active site of the enzyme and also the rate of breakdown of
the enzyme-substrate complex. Thus, it may be possible
to infer the identity of an ionizable group that participates
at the active site from the pH-activity profile for a given
enzyme.
The enzymes in living systems function at nearly con-
stant pH because they are in an environment that contains
buffers (Chapter 1).
