Carbamoyl phosphate synthase II explained

Carbamoyl-phosphate synthetase (glutamine-hydrolysing)
Ec Number:	6.3.5.5
Cas Number:	37233-48-0

Carbamoyl phosphate synthetase (glutamine-hydrolysing) 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).^{[1] [2] [3] [4] [5] [6] [7] [8]}

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

2 ATP + L-glutamine + HCO₃⁻ + H₂O

\rightleftharpoons 2 ADP + phosphate + L-glutamate + carbamoyl phosphate (overall reaction)

(1a) L-glutamine + H₂O

\rightleftharpoons L-glutamate + NH₃

(1b) 2 ATP + HCO₃⁻ + NH₃

\rightleftharpoons 2 ADP + phosphate + carbamoyl phosphate

It is activated by ATP and PRPP^[9] and it is inhibited by UTP (Uridine triphosphate)^[10] 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.^[11] It is classified under .

See also

• Carbamoyl phosphate synthetase I
• Carbamoyl phosphate synthetase III

Notes and References

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