Carbamoyl Phosphate Synthetase I.

Carbamoyl Phosphate Synthetase I.
other names	Carbamoyl phosphate synthase I. CPSase I
Existing structure data : 2YVQ , 5DOT , 5DOU
Properties of human protein
Mass / length primary structure	1462 amino acids
Cofactor	N-acetyl glutamate
Isoforms	2
Identifier
Gene name	CPS1
External IDs	OMIM :  608307 UniProt :  P31327
Enzyme classification
EC, category	6.3.4.16 ,  ligase
Response type	addition
Substrate	2 ATP + NH 3 + CO 2
Products	2 ADP + phosphate + carbamoyl phosphate
Occurrence
Parent taxon	Vertebrates
Orthologue
	human	House mouse
Entrez	1373	227231
Ensemble	ENSG00000021826	ENSMUSG00000025991
UniProt	P31327	Q8C196
Refseq (mRNA)	NM_001122633	NM_001080809
Refseq (protein)	NP_001116105	NP_001074278
Gene locus	Chr 2: 210.48 - 210.68 Mb	Chr 1: 67.12 - 67.23 Mb
PubMed search	1373	227231

Carbamoyl phosphate synthetase I (CPS 1) is the enzyme that the addition of ammonia , carbon dioxide and ATP to carbamoyl phosphate catalyzed . This reaction takes place in the mitochondria of vertebrates place and is the rate-limiting step of the urea cycle . In humans, CPS1 is mainly active in the liver and small intestine . Mutations in CPS1 - gene can CPS deficiency and for this to hyperammonemia and pulmonary hypertension lead the newborn. One variant is associated with the risk of arginine deficiency and necrotizing enterocolitis in newborns .

The CPS1 transcription is both cAMP -, as well as glucocorticoid - signaling pathways controlled. Expression of CPS1 is in the three human liver carcinoma - cell lines suppressed. CPS1 is identical to the antigen of the Hep Par 1 antibody used in surgery .

Catalyzed reaction

${\displaystyle \mathrm {HCO_{3}^{-}+ATP\longrightarrow } }$ ${\displaystyle \mathrm {ADP+HO{-}COO{-}PO_{3}^{2-}} }$

${\displaystyle \mathrm {HO{-}COO{-}PO_{3}^{2-}+NH_{3}+OH^{-}\longrightarrow } }$ ${\displaystyle \mathrm {HPO_{4}^{2-}+H_{2}N{-}COO^{-}+H_{2}O} }$

${\displaystyle \mathrm {H_{2}N{-}COO^{-}+ATP\longrightarrow } }$ ${\displaystyle \mathrm {ADP+H_{2}N{-}COO{-}PO_{3}^{2-}} }$

The reaction, which takes place in three partial steps, converts a total of two molecules of ATP and one molecule each of ammonia and carbon dioxide into two molecules of ADP and one molecule each of carbamoyl phosphate and phosphate.

Individual evidence

1. ↑ Homologues at OMA
2. ↑ UniProt P31327
3. ^ Moonen RM, Paulussen AD, Souren NY, Kessels AG, Rubio-Gozalbo ME, Villamor E: Carbamoyl phosphate synthetase polymorphisms as a risk factor for necrotizing enterocolitis . In: Pediatr Res . 62, No. 2, August 2007, pp. 188-90. doi : 10.1203 / PDR.0b013e3180a0324e . PMID 17597649 .
4. ↑ Schoneveld OJ, Hoogenkamp M, Stallen JM, Gaemers IC, Lamers WH: cyclicAMP and glucocorticoid responsiveness of the rat carbamoylphosphate synthetase gene requires the interplay of upstream regulatory units . In: Biochemistry . 89, No. 5, May 2007, pp. 574-80. doi : 10.1016 / j.biochi.2006.12.013 . PMID 17397987 .
5. ^ Butler SL, Dong H, Cardona D, et al. : The antigen for Hep Par 1 antibody is the urea cycle enzyme carbamoyl phosphate synthetase 1 . In: Lab. Invest. . 88, No. 1, January 2008, pp. 78-88. doi : 10.1038 / labinvest.3700699 . PMID 18026163 .

Web links

Wikibooks: Urea Cycle  - Learning and Teaching Materials

• D'Eustachio / Jassal / reactome: 2 ATP + NH4 + + HCO3- => 2 ADP + orthophosphate + carbamoyl phosphate [mitochondrial]