Enzymes II: Regulation
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
(Chapters 1 and 28). The
heterotropic modulators are H+, C 02, and
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.
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