Carbamoyl phosphate synthase II

Carbamoyl-phosphate synthetase (glutamine-hydrolysing)
Identifiers
EC no.	6.3.5.5
CAS no.	37233-48-0
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Search PMC articles PubMed articles NCBI proteins

carbamoyl-phosphate synthetase 1, aspartate transcarbamylase, and dihydroorotase
Identifiers
Symbol	CAD
NCBI gene	790
HGNC	1424
OMIM	114010
RefSeq	NM_004341
UniProt	P27708
Other data
Locus	Chr. 2 p21
Search for Structures Swiss-model Domains InterPro

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).^{[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 ${\displaystyle \rightleftharpoons }$ 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^[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] The CAD gene is a large gene. It uses a single strand to code for these enzyme jobs. 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)