Question

What kind of regulation is there for the synthesis of A and G nucleotides? What are the regulation targets?

Answer 1

DNA an RNA are the polymers of nucleotides. The biosynthesis of nucleotides can occur via a de novo pathway or a salvage pathway.

Amino acids, CO2, NH3, ribose-5-phosphate serve as precursors for de novo synthesis.

For purine synthesis there are 3 regulatory mechanisms -

Glutamine-PRPP amidotransferase catalyzes the transfer of an amino group to phosphoribosyl pyrophosphate (PRPP) to form phosphribosyl amine and ultimately leads to production of IMP, AMP, GMP. AMP and GMP act as inhibitors f this enzyme and act in a synergistic manner. Thus, upon excess of purines, the first step of purine synthesis is inhibited.

IMP dehydrogenase catalyxes the formation of XMP (santhylate) from IMP which finally produces GMP. Thus, GMP here acts to inhibit IMP dehydrogenase when present in excess. Also excess of AMP inhibits adenylate synthetase which catalyzes formation of AMP from IMP.

On accumulation of ADP, GDP they allosterically inhibit the enzyme ribosephosphate pyrophosphokinase which leads to formation of PRPP. Thus, this step inhibits the formation of PRPP which is the starting point og purine synthesis.