Question

Why is de novo pyrimidine nucleotide synthesis regulated at the aspartate transcarbamoylase step in bacteria and at the carbamoyl phosphate synthetase step in eukaryotes? B) Why isn’t the formation of 5-phosphoribosyl-1-pyrophosphate (PRPP) the regulated step in the de novo synthesis of purine nucleotides?

Answer 1

(A)

The formation of carbamoyl phosphate synthetase (CPS) is the most important regulatory step in the pyrimidine base formation. Higher plants have only a single form of CPS, which provides CP for both arginine and pyrimidine nucleotides. Therefore, plant CPS undergoes multiple types of regulation because one type of CP is provided to both the pathways. This needs to be highly regulated.

In the animal cells, the first step is catalyzed by aspartate transcarbamoylase (ATC). The ATC is the rate limiting step and is highly regulated. It is regulated allosterically which means the enzymes binds to another active site. ATCase is feedback inhibited by the end product. This is important because the step needs to be regulated when there is purine sufficiency and energy availability. Therefore, the UTP acts as the feedback inhibitor.

(B) This is the reason that these steps and not the other steps are highly regulated because these steps are the rate determining steps in the pathway.