carbamoylphosphatetranscarbamylase

Carbamoylphosphatetranscarbamylase refers to enzymes that transfer a carbamoyl group from carbamoyl phosphate to an amine acceptor. It is not a single enzyme but a family of related transferases known as transcarbamylases. The best characterized members are ornithine transcarbamylase (OTC), which catalyzes carbamoyl phosphate plus ornithine to form citrulline and inorganic phosphate, a key step in the urea cycle, and aspartate transcarbamylase (ATCase), which catalyzes carbamoyl phosphate plus aspartate to form N-carbamoyl-L-aspartate and phosphate in pyrimidine biosynthesis. The term thus denotes a functional group rather than a sole enzyme.

Organisms vary in subcellular localization and oligomeric state. In animals, OTC is a mitochondrial enzyme; in bacteria and plants, similar activities can be cytosolic or compartmentalized. Structural studies show that transcarbamylases commonly assemble as oligomers, and catalytic sites are often formed at subunit interfaces. The chemistry proceeds via formation of a tetrahedral intermediate as the amine substrate attacks the carbonyl carbon of the carbamoyl phosphate, with release of inorganic phosphate.

In humans, OTC participates in the urea cycle to detoxify ammonia. Deficiency of OTC causes ornithine transcarbamylase deficiency, an X-linked metabolic disorder characterized by hyperammonemia, with variable onset and severity. Management includes dietary protein restriction, ammonia scavengers, and, in severe cases, liver transplantation. More broadly, carbamoylphosphatetranscarbamylases are studied for roles in nucleotide and amino acid metabolism and as models of allosteric regulation in enzymes that utilize carbamoyl phosphate as donor.