CTP Synthase - Reaction Mechanism

Reaction Mechanism

CTP synthase catalyzes the last committed step in pyrimidine nucleotide biosynthesis:

ATP + UTP + glutamine → ADP + Pi + CTP + glutamate

It is the rate-limiting enzyme for the synthesis of cytosine nucleotides from both the de novo and uridine salvage pathways.

The reaction proceeds by the ATP-dependent phosphorylation of UTP on the 4-oxygen atom, making the 4-carbon electrophilic and vulnerable to reaction with ammonia. The source of the amino group in CTP is glutamine, which is hydrolysed in a glutamine amidotransferase domain to produce ammonia. This is then channeled through the interior of the enzyme to the synthase domain. Here, ammonia reacts with the intermediate 4-phosphoryl UTP.


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