carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity

Definition

Target type: molecularfunction

Catalysis of the reaction: 2 ATP + L-glutamine + CO2 + H2O = 2 ADP + phosphate + glutamate + carbamoyl phosphate. [EC:6.3.5.5, RHEA:18633]

Carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity is a critical enzymatic function involved in the biosynthesis of pyrimidine nucleotides, essential building blocks for DNA and RNA. This enzyme catalyzes the formation of carbamoyl phosphate, a key intermediate in the de novo biosynthesis pathway, using glutamine as the nitrogen donor. The reaction occurs in two steps:

1. **Glutamine hydrolysis:** The enzyme first hydrolyzes glutamine to glutamate and ammonia. This step involves the transfer of the amide group of glutamine to a catalytic residue, typically a cysteine.
2. **Carbamoyl phosphate synthesis:** The ammonia generated in step 1 is then used to synthesize carbamoyl phosphate from bicarbonate and ATP. This step involves the formation of a carbamate intermediate, followed by phosphorylation by ATP.

The overall reaction is:

Glutamine + bicarbonate + 2ATP → carbamoyl phosphate + glutamate + 2ADP + Pi

This reaction is essential for the synthesis of pyrimidines, and ultimately, DNA and RNA. Deficiencies in carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity can lead to genetic disorders such as ornithine transcarbamylase deficiency (OTCD), characterized by hyperammonemia and neurological complications. These disorders highlight the importance of this enzymatic activity in maintaining cellular homeostasis and normal metabolic function.'
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Proteins (2)

Compounds (1)