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Carbamoyl phosphate synthetase (glutamine-hydrolysing) (EC 6.3.5.5) is an enzyme that catalyzes the reactions that produce carbamoyl phosphate in the cytosol (as opposed to type I, which functions in the mitochondria). Its systemic name is hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating).

In pyrimidine biosynthesis, it serves as the rate-limiting enzyme and catalyzes the following reaction:

2 ATP + L-glutamine + HCO₃ + H₂O ${\displaystyle \rightleftharpoons }$ 2 ADP + phosphate + L-glutamate + carbamoyl phosphate (overall reaction)

(1a) L-glutamine + H₂O ${\displaystyle \rightleftharpoons }$ L-glutamate + NH₃

(1b) 2 ATP + HCO₃ + NH₃ ${\displaystyle \rightleftharpoons }$ 2 ADP + phosphate + carbamoyl phosphate

It is activated by ATP and PRPP and it is inhibited by UTP (Uridine triphosphate) Neither CPSI nor CPSII require biotin as a coenzyme, as seen with most carboxylation reactions.

It is one of the four functional enzymatic domains coded by the CAD gene. It is classified under EC 6.3.5.5.

See also

• Carbamoyl phosphate synthetase I
• Carbamoyl phosphate synthetase III

References

1. Anderson PM, Meister A (December 1965). "Evidence for an activated form of carbon dioxide in the reaction catalyzed by Escherichia coli carbamyl phosphate synthetase". Biochemistry. 4 (12): 2803–9. doi:10.1021/bi00888a034. PMID 5326356.
2. Kalman SM, Duffield PH, Brzozowski T (April 1966). "Purification and properties of a bacterial carbamyl phosphate synthetase". The Journal of Biological Chemistry. 241 (8): 1871–7. doi:10.1016/S0021-9258(18)96716-5. PMID 5329589.
3. Yip MC, Knox WE (May 1970). "Glutamine-dependent carbamyl phosphate synthetase. Properties and distribution in normal and neoplastic rat tissues". The Journal of Biological Chemistry. 245 (9): 2199–204. doi:10.1016/S0021-9258(18)63139-4. PMID 5442268.
4. Stapleton MA, Javid-Majd F, Harmon MF, Hanks BA, Grahmann JL, Mullins LS, Raushel FM (November 1996). "Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase". Biochemistry. 35 (45): 14352–61. doi:10.1021/bi961183y. PMID 8916922.
5. Holden HM, Thoden JB, Raushel FM (December 1998). "Carbamoyl phosphate synthetase: a tunnel runs through it". Current Opinion in Structural Biology. 8 (6): 679–85. doi:10.1016/s0959-440x(98)80086-9. PMID 9914247.
6. Raushel FM, Thoden JB, Reinhart GD, Holden HM (October 1998). "Carbamoyl phosphate synthetase: a crooked path from substrates to products". Current Opinion in Chemical Biology. 2 (5): 624–32. doi:10.1016/s1367-5931(98)80094-x. PMID 9818189.
7. Raushel FM, Thoden JB, Holden HM (June 1999). "The amidotransferase family of enzymes: molecular machines for the production and delivery of ammonia". Biochemistry. 38 (25): 7891–9. doi:10.1021/bi990871p. PMID 10387030.
8. Thoden JB, Huang X, Raushel FM, Holden HM (October 2002). "Carbamoyl-phosphate synthetase. Creation of an escape route for ammonia". The Journal of Biological Chemistry. 277 (42): 39722–7. doi:10.1074/jbc.M206915200. PMID 12130656.
9. Inkling. "Unsupported Browser". Inkling. Retrieved 25 April 2018.
10. Engelking LR. Pyrimidine biosynthesis. Textbook of Veterinary Physiological Chemistry. 2015;:83–7. https://doi.org/10.1016/B978-0-12-391909-0.50014-1 Retrieved 1 April 2023
11. Moreno-Morcillo M, Grande-García A, Ruiz-Ramos A, del Caño-Ochoa F, Boskovic J, Ramón-Maiques S (2017). "Structural Insight into the Core of CAD, the Multifunctional Protein Leading De Novo Pyrimidine Biosynthesis". Structure. 25 (6): 912–923. doi:10.1016/j.str.2017.04.012. hdl:10261/166586. PMID 28591622.

External links

• Carbamoyl-Phosphate+Synthase+(Glutamine-Hydrolyzing) at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

• Biology

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• Genes on human chromosome 2
• EC 6.3.5
• Ligase stubs