Physical Chemistry Third Edition

580 13 Chemical Reaction Mechanisms II: Catalysis and Miscellaneous Topics

Use the data of Example 13.5 to make a linear least-squares fit ofri/[R] as a function ofri. Find

the value of the Michaelis–Menten constant for the reaction of Example 13.5 and compare it

with the value from the Lineweaver–Burk plot of Example 13.5.

aG. S. Eadie,J. Biol. Chem., 146 , 85 (1942).

Enzyme Inhibition

Many enzyme-catalyzed reactions are subject toinhibition. That is, the rate of the

process is decreased by the presence of some substance, which is called aninhibitor.

Thedegree of inhibitionis defined as

i 1 −

r

r 0

(13.1-49)

whereris the rate of the catalyzed reaction in the presence of the inhibitor and r 0 is

the rate in the absence of the inhibitor. Acompetitive inhibitoris one for which the

degree of inhibition decreases if the reactant concentration is increased with constant

concentration of the inhibitor. Anoncompetitive inhibitoris one for which the degree of

inhibition is independent of the reactant concentration, and ananticompetitive inhibitor

is one for which the degree of inhibition increases if the concentration of the reactant

is increased.

CH 3

CH 3

Acetylcholine

CH 3 N+CH 2 CH 2 O C CH 3

O

HF

CH 3 H

Diisopropyl fluorophosphate

CH 3 CH 3

CH 3

CCO P O

O

Figure 13.9 The Structural For-
mulas of Acetylcholine and Diiso-
propyl Fluorophosphate.

The accepted mechanism for competitive inhibition is that the inhibitor can occupy

the same active site as the reactant.Acetylcholineis aneurotransmitter(a substance that

diffuses across the synapse between two nerve cells and triggers a signal in the second

nerve cell). This substance is hydrolyzed by the enzymecholinesterase, which causes

the signal to be ended by lowering the concentration of acetylcholine. Figure 13.9

shows the structural formulas of acetylcholine and of diisopropyl fluorophosphate,

which is a competitive inhibitor for this hydrolysis. The diisopropyl fluorophosphate

molecules compete with the acetylcholine molecules for the active sites, which inhibits

the catalyzed reaction since those enzyme molecules with diisopropyl fluorophosphate

molecules in their active sites are not available for acetylcholine hydrolysis. With suffi-

cient inhibition the neurotransmitter remains in the synapse and the nerve cell transmits

a signal repeatedly. If the nerve cell repeatedly stimulates a muscle to contract the mus-

cle soon succumbs to fatigue and the organism could die. Various substances similar

to diisopropyl fluorophosphate have been prepared as insecticides and as chemical

warfare agents (“nerve gases”).

A proposed mechanism for a noncompetitive inhibitor is that an enzyme has a second

site, other than the catalytic active site, to which the inhibitor can bind. The inhibited

enzyme molecule is assumed unable to catalyze the reaction, although the active site

is not occupied.

PROBLEMS

Section 13.1: Catalysis

13.1 a.The hydrogenation of ethylene on a copper surface

appears to follow the Langmuir–Hinshelwood

mechanism, with the rate law

rate

ka[H 2 ][C 2 H 4 ]

( 1 +kb[C 2 H 4 ])^2

What conclusion can you draw from this rate law?