Question

14. Describe how the synthesis of nucleotides is regulated.

Answer 1

*Regulatiom of pyrimidine synthesis

ln bacteria, aspartate transcarbamoylase
(ATCase) catalyses a committed step in pyrimidine biosynthesis. ATCase is a good
example of an enzyme controlled by
feedhack mechanism by the end product
CTP. In certain bacteria, UTP also inhibits
ATCase. ATP, however, stimulates ATCase
activity.
Carbamoyl phosphate synthetase II (CPS II) is
the regulatory enzyme of pyrimidine synthesis in
animals. lt is activated by PRPP and ATP and
inhibited by UDP and UTP. OMP decarboxylase,
inhibited by UMP and CMP, also controls
pyrimidine formation.

*Regulation of purine
nucleotide biosynthesis:

The purine nucleotide synthesis is well
coordinated to meet the cellular demands. The
intracellular concentration of PRPP regulates
purine synthesis to a large extent. This, in turn,
is dependent on the availability of ribose
S-phosphate and the enzyme PRPP synthetase.
  
PRPP glutamyl amidotransferase is controlled
by a feedback mechanism by purine nucleotides.
That is, if AMP and CMP are available in
adequate amounts to meet the cellular
requirements, their synthesis is turned off at the
amidotransferase reaction.

Another important stage of regulation is in the
conversion of IMP to AMP and CMP. AMP
inhibits adenylsuccinate synthetase while CMP
inhibits IMP dehydrogenase. Thus, AMP and
CMP control their respective synthesis from IMP
by a feedback mechanism.

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