Cellular Structure, Proteins, and Metabolism
77
Because different enzymes have different concentrations
and activities, it would be extremely unlikely that the reac-
tion rates of all these steps would be exactly the same. Thus,
one step is likely to be slower than all the others. This step is
known as the
rate-limiting reaction
in a metabolic pathway.
None of the reactions that occur later in the sequence, includ-
ing the formation of end product, can proceed more rapidly
than the rate-limiting reaction because their substrates are sup-
plied by the previous steps. By regulating the concentration or
activity of the rate-limiting enzyme, the rate of fl ow through
the whole pathway can be increased or decreased. Thus, it is
not necessary to alter all the enzymes in a metabolic pathway
to control the rate at which the end product is produced.
Rate-limiting enzymes are often the sites of allosteric or
covalent regulation. For example, if enzyme e
2
is rate-limiting in
the pathway just described, and if the end product E inhibits the
activity of e
2
,
end-product inhibition
occurs (
Figure 3–39
).
As the concentration of the product increases, the inhibition of
further product formation increases. Such inhibition, which is
a form of negative feedback (Chapter 1), frequently occurs in
synthetic pathways where the formation of end product is effec-
tively shut down when it is not being utilized. This prevents
unnecessary excessive accumulation of the end product.
Control of enzyme activity also can be critical for
revers-
ing
a metabolic pathway. Consider the pathway we have been
discussing, ignoring the presence of end-product inhibition of
enzyme e
2
. The pathway consists of three reversible reactions
mediated by e
1
, e
2
, and e
3
, followed by an irreversible reaction
mediated by enzyme e
4
. E can be converted into D, however,
if the reaction is coupled to the simultaneous breakdown of
a molecule that releases large quantities of energy. In other
words, an irreversible step can be “reversed” by an alternative
route, using a second enzyme and its substrate to provide the
large amount of required energy. Two such high-energy irre-
versible reactions are indicated by bowed arrows to emphasize
that two separate enzymes are involved in the two directions:
C
B
A
D
E
Y
X
e
1
e
3
e
4
e
5
e
2
The direction of fl ow through the pathway can be regu-
lated by controlling the concentration and/or activities of e
4
and e
5
. If e
4
is activated and e
5
inhibited, the fl
ow will proceed
from A to E, whereas inhibition of e
4
and activation of e
5
will
produce fl ow from E to A.
Another situation involving the differential control of
several enzymes arises when there is a branch in a metabolic
pathway. A single metabolite, C, may be the substrate for more
than one enzyme, as illustrated by the pathway:
C
B
A
D
E
FG
e
1
e
3
e
4
e
6
e
7
e
2
Altering the concentration and/or activities of e
3
and e
6
regu-
lates the fl ow of metabolite C through the two branches of the
pathway.
Considering the thousands of reactions that occur in
the body and the permutations and combinations of possible
control points, the overall result is staggering. The details of
regulating the many metabolic pathways at the enzymatic
level are beyond the scope of this book. In the remainder of
this chapter, we consider only (1) the overall characteristics of
the pathways by which cells obtain energy, and (2) the major
pathways by which carbohydrates, fats, and proteins are bro-
ken down and synthesized.
SECTION D SUMMARY
In adults, the rates at which organic molecules are continuously
synthesized (anabolism) and broken down (catabolism) are
approximately equal.
Chemical Reactions
I. The difference in the energy content of reactants and products
is the amount of energy (measured in calories) released or
added during a reaction.
II. The energy released during a chemical reaction is either
released as heat or transferred to other molecules.
III. The four factors that can alter the rate of a chemical reaction
are listed in Table 3–5.
IV. The activation energy required to initiate the breaking of
chemical bonds in a reaction is usually acquired through
collisions between molecules.
V. Catalysts increase the rate of a reaction by lowering the
activation energy.
VI. The characteristics of reversible and irreversible reactions are
listed in Table 3–6.
VII. The net direction in which a reaction proceeds can be altered,
according to the law of mass action, by increases or decreases
in the concentrations of reactants or products.
Enzymes
I. Nearly all chemical reactions in the body are catalyzed by
enzymes, the characteristics of which are summarized in
Table 3–7.
II. Some enzymes require small concentrations of cofactors for
activity.
C
B
AD
E
e
1
e
3
e
4
Rate-limiting
enzyme
End product
(modulator
molecule)
Inhibition
of
e
2
e
2
Figure 3–39
End-product inhibition of the rate-limiting enzyme in a metabolic
pathway. The end product E becomes the modulator molecule that
produces inhibition of enzyme e
2
.
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