Question

ATCase is an important enzyme in DNA replication.

a) What does this enzyme do and what are its substrates?

b) This enzyme demonstrates feedback regulation. Describe its quaternary structure in this regard.

c) Besides substrate(s) and product, what other molecules are involved in the feedback regulation of ATCase? Describe their function and how they interact?

Answer 1

1. Aspartate transcarbamoylase (ATCase) is an enzyme found in the cytosol. It catalyzes the first committed step of pyrimidine synthesis, which is the condensation of L-aspartate and carbamoyl phosphate (CP) to produce N-carbamoyl-L-aspartate.

The substrate of this enzyme is L-aspartate and carbamoyl phosphate (CP)

2. ATcase catalyzes the first step in the biosynthesis of pyrimidines, which is allosterically regulated. ATcase yields pyrimidine nucleotides such as CTP. Regulation of the production of CTP is needed in the cell because it is an energetically expensive process. If CTP is present in higher concentration it inhibits the first step of the reaction ie. reaction catalyzed by ATcase. This is called feed-back inhibition. CTP binds to an allosteric/regulatory site rather than the active site of the enzyme to inhibit the reaction.
3. Surplus of pyrimidine is prevented by allosteric regulation of ATCase with the aid of CTP and UTP. Alternatively, adenosine triphosphate (ATP) and guanosine triphosphate (GTP) which are the end-products of the parallel purine biosynthesis stimulates ATCase activity. Transition-state analog N-(phosphonacetyl)-L-aspartate (PALA) is also reported to regulate formation of CTP, these are also called mechanism based inactivators.