10.3. Molecular implementation of mechanical principles[[Student version, January 17, 2003]] 373
40701000.0032 0.0033 0.0034 0.0035 0.0036initial velocity, arbitrary scale1/T, K-1101000.0032 0.0033 0.0034 0.0035initial velocity, arbitrary scale1/T, K-1a b
20020Figure 10.15:(Experimental data.) (a)Semilog plot of initial reaction velocity versus inverse temperature for the
conversion ofl-malate to fumarate by the enzyme , at pH 6.35. (b)The same for the reverse reaction. The first
reaction follows the Arrhenius rate law (Equation 10.11), as shown by the straight line. The line is the function
log 10 v 0 =const−(3650K/T), corresponding to an activation barrier of 29kBTr. The second reaction shows two
different slopes; presumably an alternative reaction mechanism becomes available at temperatures above 294K.[Data
from Dixon & Webb, 1979.]
SE ES EP EPFigure 10.16: (Schematic.) Conceptual model of enzyme activity. (a)The enzyme E has a binding site with
ashape and distribution of charges, hydrophobicity, and H-bonding sites approximately matching those presented
bythe substrate S. (b)Tomatch perfectly, however, S (or both E and S) must deform. (Other, more dramatic
conformational changes in the enzyme are possible too.) One bond in the substrate (shown as a spring in S) stretches
close to its breaking point. (c)From the ES state, then, a thermal fluctuation can readily break the stretched bond,
giving rise to the EP complex. A new bond can now form (upper spring), stabilizing the product P. (d)The P state
is not a perfect fit to the binding site either, so it readily unbinds, returning E to its original state.
10.3.3 An enzyme catalyzes a reaction by binding to the transition state
Reaction rates are controlled by activation barriers, with a temperature dependence given roughly
byan Arrhenius exponential factor (see Section 3.2.4 on page 79). Enzymes increase reaction rates,
but maintain that characteristic temperature dependence (Figure 10.15). Thus it’s reasonable to
guess thatenzymes work by reducing the activation barrier to a reaction.What may not be so clear
ishowthey could accomplish such a reduction.
Figure 10.16 summarizes a mechanism proposed by J. Haldane in 1930. Using the mechanical