76
Chapter 3
Figure 3–36
illustrates the effect of increasing the affi n-
ity of an enzyme’s active site without changing the substrate
or enzyme concentration. If the substrate concentration is less
than the saturating concentration, the increased affi nity of the
enzyme’s binding site results in an increased number of active
sites bound to substrate, and thus an increase in the reaction
rate.
The regulation of metabolism through the control of
enzyme activity is an extremely complex process because, in
many cases, more than one agent can alter the activity of an
enzyme (
Figure 3–37
). The modulator molecules that allo-
sterically alter enzyme activities may be product molecules of
other cellular reactions. The result is that the overall rates of
metabolism can adjust to meet various metabolic demands.
In contrast, covalent modulation of enzyme activity is medi-
ated by protein kinase enzymes that are themselves activated
by various chemical signals the cell receives, for example, from
a hormone.
Figure 3–38
summarizes the factors that regulate the
rate of an enzyme-mediated reaction.
Multienzyme Reactions
The sequence of enzyme-mediated reactions leading to the
formation of a particular product is known as a
metabolic
pathway.
For example, the 19 reactions that convert glucose
to carbon dioxide and water constitute the metabolic pathway
for glucose catabolism. Each reaction produces only a small
change in the structure of the substrate. By such a sequence of
small steps, a complex chemical structure, such as glucose, can
be transformed to the relatively simple molecular structures
carbon dioxide and water.
Consider a metabolic pathway containing four enzymes
(e
1
, e
2
, e
3
, and e
4
) and leading from an initial substrate A to the
end product E, through a series of intermediates, B, C, and D:
e
1
e
2
e
3
e
4
A
3::4
B
3::4
C
3::4
D
⎯⎯→
E
(The irreversibility of the last reaction is of no consequence
for the moment.) By mass action, increasing the concentra-
tion of A will lead to an increase in the concentration of B
(provided e
1
is not already saturated with substrate), and so on
until eventually there is an increase in the concentration of the
end product E.
Initial affinity
Increased
affinity
Substrate concentration
Reaction rate
Figure 3–36
At a constant substrate concentration, increasing the affi nity of
an enzyme for its substrate by allosteric or covalent modulation
increases the rate of the enzyme-mediated reaction. Note that
increasing the enzyme’s affi nity does not increase the
maximal
rate
of the enzyme-mediated reaction.
Active site
Site of
covalent
activation
Sites of
allosteric
activation
Sites of
allosteric
inhibition
Site of
covalent
inhibition
Enzyme
Figure 3–37
On a single enzyme, multiple sites can modulate enzyme activity,
and therefore the reaction rate, by allosteric and covalent activation
or inhibition.
Enzyme concentration
(enzyme synthesis,
enzyme breakdown)
Enzyme activity
(allosteric activation or inhibition,
covalent activation or inhibition)
Product
(product
concentration)
Substrate
(substrate
concentration)
(rate)
Figure 3–38
Factors that affect the rate of enzyme-mediated reactions.
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