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Information on EC 6.3.4.16 - carbamoyl-phosphate synthase (ammonia) and Organism(s) Mus musculus and UniProt Accession Q8C196

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EC Tree
IUBMB Comments
The enzyme catalyses the first committed step in the urea cycle. The reaction proceeds via three separate chemical reactions: phosphorylation of hydrogencarbonate to carboxyphosphate; a nucleophilic attack of ammonia on carboxyphosphate yielding carbamate; and the phosphorylation of carbamate forming carbamoyl phosphate. Two moles of ATP are utilized for the synthesis of one molecule of carbamyl phosphate, making the reaction essentially irreversible. The enzyme requires the allosteric activator N-acetyl-L-glutamate. cf. EC 6.3.5.5, carbamoyl-phosphate synthase (glutamine-hydrolysing).
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This record set is specific for:
Mus musculus
UNIPROT: Q8C196
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The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
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2
ATP
+
NH3
+
hydrogencarbonate
=
2
ADP
+
phosphate
+
carbamoyl phosphate
2
+
+
=
2
+
+
Synonyms
carbamoyl phosphate synthetase, cpsase, carbamoyl-phosphate synthetase, carbamoylphosphate synthetase, cps i, cps-i, carbamyl phosphate synthetase i, cps-1, carbamoylphosphate synthase, carbamoyl phosphate synthetase i, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carbamoyl phosphate synthetase 1
-
carbamoyl phosphate synthase-1
-
-
carbamoyl phosphate synthetase 1
-
-
Carbamoyl-phosphate synthetase I
-
-
-
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Carbamoylphosphate synthase
-
-
-
-
Carbamoylphosphate synthase (ammonia)
-
-
-
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Carbamoylphosphate synthetase (ammonia)
-
-
-
-
Carbamoylphosphate synthetase I
-
-
-
-
Carbamyl phosphate synthase I
-
-
-
-
Carbamylphosphate synthetase
-
-
-
-
Carbamylphosphate synthetase I
-
-
-
-
carbmoylphosphate synthetase
-
-
-
-
Carbon-dioxide-ammonia ligase
-
-
-
-
Carbonate kinase (phosphorylating)
-
-
-
-
CPS I
-
-
-
-
CPS-1
-
-
CPS1
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
amination
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
carbon-dioxide:ammonia ligase (ADP-forming, carbamate-phosphorylating)
The enzyme catalyses the first committed step in the urea cycle. The reaction proceeds via three separate chemical reactions: phosphorylation of hydrogencarbonate to carboxyphosphate; a nucleophilic attack of ammonia on carboxyphosphate yielding carbamate; and the phosphorylation of carbamate forming carbamoyl phosphate. Two moles of ATP are utilized for the synthesis of one molecule of carbamyl phosphate, making the reaction essentially irreversible. The enzyme requires the allosteric activator N-acetyl-L-glutamate. cf. EC 6.3.5.5, carbamoyl-phosphate synthase (glutamine-hydrolysing).
CAS REGISTRY NUMBER
COMMENTARY hide
9026-23-7
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + NH4+ + HCO3- + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
2 ATP + NH3 + CO2 + H2O
2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + NH4+ + HCO3- + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
2 ATP + NH3 + CO2 + H2O
2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
peroxynitrite
CPS1 activity is decreased by treatment with peroxynitrite in a peroxynitrite concentration- and time-dependent manner due to tyrosine nitration (47% decrease in 1 min and 60% decrease in 10 min with 1 mM peroxynitrite)
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
N-acetyl-L-glutamate
nitration at Y1450 in an alpha-helix of allosteric domain prevents activation of CPS1 by N-acetyl-L-glutamate
acetylglutamate
-
-
N-acetyl-L-glutamate
-
i.e. NAG, dependent on the essential cofactor
SIRT5
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CPSM_MOUSE
1500
0
164618
Swiss-Prot
Mitochondrion (Reliability: 3)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
acetylation
-
mitochondrial CPSI is acetylated, and activated by deacetylation through SIRT5, overview
additional information
-
deacetylation by SIRT5 activates CPSI
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
overexpression of SIRT5 in mice leads to increased deacetylation and activation of CPS1 protein in liver of transgenic mice compared to wild-type mice. Urea production is upregulated in hepatocytes of SIRT5 transgenic mice
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
nobiletin is able to lower serum ammonia levels in mice fed with regular chow (RC), high-fat (HFD) or high-protein diet. NOB rescues CPS1 protein levels under the HFD condition via induction of the transcription factors C/EBPalpha and C/EBPbeta. HPD markedly increases CPS1 levels relative to RC. A functional circadian clock, is required for nobiletin induction of CPS1 under the HFD condition
nutrient depletion does not increase CPS1 protein levels in wild-type or KO cells
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Tatibana, M.; Shigesada, K.
Two carbamyl phosphate synthetases of mammals: specific roles in control of pyrimidine and urea biosynthesis
Adv. Enzyme Regul.
10
249-271
1972
Mammalia, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Crouser, E.D.; Julian, M.W.; Huff, J.E.; Struck, J.; Cook, C.H.
Carbamoyl phosphate synthase-1: a marker of mitochondrial damage and depletion in the liver during sepsis
Crit. Care Med.
34
2439-2446
2006
Mus musculus
Manually annotated by BRENDA team
Ogura, M.; Nakamura, Y.; Tanaka, D.; Zhuang, X.; Fujita, Y.; Obara, A.; Hamasaki, A.; Hosokawa, M.; Inagaki, N.
Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1
Biochem. Biophys. Res. Commun.
393
73-78
2010
Mus musculus, Mus musculus C57BL/6
Manually annotated by BRENDA team
Nakagawa, T.; Lomb, D.J.; Haigis, M.C.; Guarente, L.
SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle
Cell
137
560-570
2009
Mus musculus
Manually annotated by BRENDA team
Takakusa, H.; Mohar, I.; Kavanagh, T.J.; Kelly, E.J.; Kaspera, R.; Nelson, S.D.
Protein tyrosine nitration of mitochondrial carbamoyl phosphate synthetase 1 and its functional consequences
Biochem. Biophys. Res. Commun.
420
54-60
2012
Mus musculus (Q8C196), Mus musculus
Manually annotated by BRENDA team
Nohara, K.; Shin, Y.; Park, N.; Jeong, K.; He, B.; Koike, N.; Yoo, S.; Chen, Z.
Ammonia-lowering activities and carbamoyl phosphate synthetase 1 (Cps1) induction mechanism of a natural flavonoid
Nutr. Metab.
12
23
2015
Mus musculus (Q8C196), Mus musculus
Manually annotated by BRENDA team