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CHAPTER 7

Enzymes II: Regulation

(b)

FIGURE 7-5

Schematic representation of the subunit structure of aspartate transcarbamoylase and its dissociation into catalytic and

regulatory subunits by mercurials, which can be further converted to inactive monomeric subunits by strong denaturing

agents (e.g., sodium dodecyl sulfate). The native enzyme consists of two catalytic trimers placed one above the other,

along with three dimeric regulatory subunits surrounding the catalytic trimers in an equatorial plane (a). Substrate

maintains the enzyme in the catalytically more active relaxed (R) conformation, while cytidine triphosphate maintains it

in the catalytically less active taut (T) conformation (b). [Reproduced, with permission from E. L. Smith, R. L. Hill,

I. R. Lehman, et al:

P rin cip les o f B io ch em istry: G en era l A sp ects,

7th ed. McGraw-Hill, New York, 1983].

substrates, without altering Vmax. The biological

significance of the activation by the purine nucleotide

ATP can be appreciated, since both ATP and CTP

are eventually utilized in the biosynthesis of

double-helical DNA, which contains equal amounts

of purines and pyrimidines. Thus, modulation of

ATCase activity equalizes the rates of formation of

purine and pyrimidine nucleotides. Other regulatory

and metabolic aspects of purines and pyrimidines are

discussed in Chapter 27.

2. Hemoglobin binding of oxygen is a classic example

of the homotropic effect. Hemoglobin also shows

heterotropic effects with specific molecules in its

environment. These effects are intimately related to

the function of hemoglobin as a carrier not only of

oxygen but of H+ and CO

2

(Chapters 1 and 28). The

heterotropic modulators are H+, C 02, and

FIGURE 7-6

Relationship between the initial velocity (v) of aspartate

transcarbamoylase and the substrate concentration. Note that ATP is a

positive allosteric modulator, which causes decreased

, whereas

CTP is a negative allosteric modulator, which causes increased /fo.s.