Question

Compare the regulation of the pyrimidine synthesis pathway in bacteria and mammals. What is similar, and what is different? Consider the enzymes involved, and the reactions they carry out (what happens in the reactions), as well as the kind of regulation. What is one of the enzymes “famous” for? Explain.

Answer 1

Pyrimidine synthesis in bacteria is regulated at aspartate transcarbamoylase (ATCase) which converts carbamoyl phosphate into cabamoyl aspartate with the help of an aspartate. ATCase is inhibited by UTP through feedback regulation and stimulated by ATP through allosteric stimulation.

In animals, pyrimidine synthesis is regulated at carbamoyl phosphate synthetase II (CPS II), not ATCase. CPS II converts CO2 and amino group of glutamine into carbamoyl phosphate while releasing glutamate with the help of ATP. CPS II is inhibited by UDP and UTP and stimulated by ATP and PRPP. There is another one form of CPS which is CPS I that catalyses a similar reaction in the urea cycle. CPS I gets amino group from glutamate, while CPS II from glutamine.

ATCase is famous for allosteric regulation. It has allosteric sites for CTP and ATP. CTP inhibits its activity, while ATP stimulates its activity. If CTP level is high, it inhibits the ATCase, if the level goes down, CTP moves away from the enzyme. ATP regulates both purine and pyrimidine synthesis. If ATP level is more than that of CTP, ATP stimulate ATCase to generate more CTP.