From the Research
The primary regulatory enzyme of pyrimidine synthesis is Carbamoyl phosphate synthetase II (CPS II). This enzyme catalyzes the first committed step in the de novo pyrimidine biosynthetic pathway, converting glutamine, bicarbonate, and ATP to carbamoyl phosphate. According to the most recent study 1, CPS II is part of a multienzymatic protein called CAD, which carries the enzymatic activities for the first three steps in the de novo biosynthesis of pyrimidine nucleotides. The regulatory mechanism of CPS II allows the cell to adjust pyrimidine synthesis based on cellular needs, making it a potential target for chemotherapeutic agents that aim to disrupt nucleotide metabolism in rapidly dividing cells.
Some key points about CPS II include:
- It is allosterically regulated, being activated by ATP and PRPP (phosphoribosyl pyrophosphate) and inhibited by UTP, which serves as a feedback inhibitor when pyrimidine levels are sufficient 2.
- CPS II differs from CPS I, which functions in the urea cycle, by its location in the cytosol rather than mitochondria and by its regulatory properties 3.
- The enzyme's critical role in controlling the rate of pyrimidine synthesis makes it a potential target for chemotherapeutic agents that aim to disrupt nucleotide metabolism in rapidly dividing cells 4.
- Recent studies have shown that CAD, the multienzymatic protein that includes CPS II, is regulated by the mitogen-activated protein (MAP) kinase cascade, which plays a key role in cell growth and proliferation 2.
Overall, the evidence suggests that CPS II is the primary regulatory enzyme of pyrimidine synthesis, and its regulation is crucial for cell growth and proliferation.