BioPHYSICAL chemistry

(singke) #1
slopes have changed according to the apparent change in KM. For the
uncompetitive inhibitor, theapparent maximum velocity is decreased while
the value of KMis unchanged. On the double-reciprocal plot, the apparent
change in the maximum velocity will alter the yintercept of the line but
the slope of the line will remain unchanged. In practice, enzymes may
have more than one substrate-binding position and so the presence of an
inhibitor may have mixed contributions.
Inhibitors may also be irreversible and thus destroy an enzyme func-
tion. A special class of irreversible inhibitors are suicide inactivators. These
compounds are unreactive until they bind to the active site of a particular
enzyme. By design, the compound is not transformed into the normal
product but into a reactive compound that combines irreversibly to the
enzyme. Suicide inactivators play a critical role in the design of drugs as
such inhibitors are specific and are less likely to have side effects than drugs
with nonspecific action.

Research direction: the RNA world


The prebiotic world of the primitive Earth was significantly different than
the Earth of today. Among the many unanswered questions concern-
ing the earliest times of the Earth is how did life begin? The prebiotic
environment may have contained basic building blocks, such as amino
acids, sugars, purines, and pyrimidines (Figure 7.19). Although these
may have combined to form short-lived polymers, the Earth at that time
would not have had the chemically complex molecules found today, such
as proteins or chromosomes. Of particular interest concerning early times

158 PARTI THERMODYNAMICS AND KINETICS


Vmax

1

Vmax

α

V 0

1

Inhibitor

Uncompetitive

No inhibitor

KM
Slope 
Vmax

[S]

1

Figure 7.18A competitive inhibitor results in a shift in the slope but not the yintercept (right)
whereas an uncompetitive inhibitor shifts the yintercept but not the slope (left).


Vmax

1

V 0

(^1) Inhibitor
No inhibitor
αKM
Slope 
Vmax
[S]
1
Competitive

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