Carbamoyl phosphate synthase II

Carbamoyl-phosphate synthetase (glutamine-hydrolysing)
Identifiers
EC number	6.3.5.5
CAS number	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
Entrez	790
HUGO	1424
OMIM	114010
RefSeq	NM_004341
UniProt	P27708
Other data
Locus	Chr. 2 p21

Carbamoyl phosphate synthetase II (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 $\rightleftharpoons$ 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 UMP (Uridine monophosphate, the end product of the pyrimidine synthesis pathway).

Neither CPSI nor CPSII require biotin as a coenzyme, as seen with most carboxylation reactions.

It is one of the three enzyme functions coded by the CAD gene. It is classified under EC 6.3.5.5.

Nomenclature

Carbamoyl-phosphate synthetase (glutamine-hydrolysing) is also known as:

• hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)
• carbamyl phosphate synthetase (glutamine)
• glutamine-dependent carbamyl phosphate synthetase
• carbamoyl phosphate synthetase
• CPS
• carbon-dioxide:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)

References

1. Anderson, P.M.; Meister, A. (1965). "Evidence for an activated form of carbon dioxide in the reaction catalysed by Escherichia coli carbamyl phosphate synthetase". Biochemistry. 4 (12): 2803–2809. doi:10.1021/bi00888a034. PMID 5326356.
2. Kalman, S.M.; Duffield, P.H.; Brzozowski, T. (1966). "Purification and properties of a bacterial carbamyl phosphate synthetase". J. Biol. Chem. 241 (8): 1871–1877. PMID 5329589.
3. Yip, M.C.M.; Knox, W.E. (1970). "Glutamine-dependent carbamyl phosphate synthetase. Properties and distribution in normal and neoplastic rat tissues". J. Biol. Chem. 245 (9): 2199–2204. PMID 5442268.
4. Stapleton, M.A.; Javid-Majd, F.; Harmon, M.F.; Hanks, B.A.; Grahmann, J.L.; Mullins, L.S.; Raushel, F.M. (1996). "Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase". Biochemistry. 35: 14352–14361. doi:10.1021/bi961183y. PMID 8916922.
5. Holden, H.M.; Thoden, J.B.; Raushel, F.M. (1998). "Carbamoyl phosphate synthetase: a tunnel runs through it". Curr. Opin. Struct. Biol. 8 (6): 679–685. doi:10.1016/s0959-440x(98)80086-9. PMID 9914247.
6. Raushel, F.M.; Thoden, J.B.; Reinhart, G.D.; Holden, H.M. (1998). "Carbamoyl phosphate synthetase: a crooked path from substrates to products". Curr. Opin. Chem. Biol. 2 (5): 624–632. doi:10.1016/s1367-5931(98)80094-x. PMID 9818189.
7. Raushel, F.M.; Thoden, J.B.; Holden, H.M. (1999). "The amidotransferase family of enzymes: molecular machines for the production and delivery of ammonia". Biochemistry. 38: 7891–7899. doi:10.1021/bi990871p. PMID 10387030.
8. Thoden, J.B.; Huang, X.; Raushel, F.M.; Holden, H.M. (2002). "Carbamoyl-phosphate synthetase. Creation of an escape route for ammonia". J. Biol. Chem. 277 (42): 39722–39727. doi:10.1074/jbc.M206915200. PMID 12130656.
9. https://www.inkling.com/read/illustrated-reviews-biochemistry-harvey-5th/chapter-22/pyrimidine-synthesis-and

External links

• Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) at the US National Library of Medicine Medical Subject Headings (MeSH)