Information on EC 6.3.4.16 - Carbamoyl-phosphate synthase (ammonia)

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea

EC NUMBER
COMMENTARY
6.3.4.16
-
RECOMMENDED NAME
GeneOntology No.
Carbamoyl-phosphate synthase (ammonia)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 ATP + NH3 + CO2 + H2O = 2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
2 ATP + NH3 + CO2 + H2O = 2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
depending on their physiological role, carbonyl phosphate synthetases use either glutamine or free ammonia as the nitrogen donor for carbamoyl phosphate synthesis, all enzymes contain the structurally equivalent of a triad-type glutamine amidotransferase, GAT, domain
-
2 ATP + NH3 + CO2 + H2O = 2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
depending on their physiological role, carbonyl phosphate synthetases uses either glutamine or free ammonia as the nitrogen donor for carbamoyl phosphate synthesis, all enzymes contain the structurell equivalent of a triad-type glutamine amidotransferase, GAT, domain
-
2 ATP + NH3 + CO2 + H2O = 2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
depending on their physiological role, carbonyl phosphate synthetasese uses either glutamine or free ammonia as the nitrogen donor for carbamoyl phosphate synthesis, all enzymes contain the structurell equivalent of a triad-type glutamine amidotransferase, GAT, domain
-
2 ATP + NH3 + CO2 + H2O = 2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
non-glutamine-utilizing enzymes, lacking the catalytic cysteine residue, can generate carbamoyl phosphate only in presence of free ammonia
-
2 ATP + NH3 + CO2 + H2O = 2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
the enzyme is enzymologically and structurally a carbamate kinase, stoichiometry
-
2 ATP + NH3 + CO2 + H2O = 2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
the enzyme structure is ill-suited for catalysing the characteristic three-step reaction of carbamoyl-phosphate synthetase and supports the view that the carbamate kinase-like carbamoyl-phosphate synthetase is in fact a highly thermostable and very slow carbamate kinase that, in extreme environment of Pyrococcus furiosus, may have the new function of making, rather than using, carbamoyl phosphate
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
amination
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Alanine, aspartate and glutamate metabolism
-
-
Arginine and proline metabolism
-
-
Metabolic pathways
-
-
Microbial metabolism in diverse environments
-
-
Nitrogen metabolism
-
-
urea cycle
-
-
urea cycle
-
-
SYSTEMATIC NAME
IUBMB Comments
Carbon-dioxide:ammonia ligase (ADP-forming, carbamate-phosphorylating)
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
arginine-specific CPS
P31327
-
CarB
A5UK38
gene name
carbamate kinase-like carbamoyl phosphate synthetase
Q9UWF8
this enzyme is a intermediary form between carbamate kinase and carbamoyl phosphate synthetase
carbamate kinase-like carbamoyl-phosphate synthetase
-
-
carbamoyl phosphate synthase-1
-
-
carbamoyl phosphate synthetase
-
-
carbamoyl phosphate synthetase
P31327
-
carbamoyl phosphate synthetase
A5UK38
-
carbamoyl phosphate synthetase
-
-
carbamoyl phosphate synthetase 1
-
-
carbamoyl phosphate synthetase 1
-
-
carbamoyl phosphate synthetase 1
Q8C196
-
carbamoyl phosphate synthetase 1
Mus musculus C57BL/6
-
-
-
carbamoyl phosphate synthetase 1
-
-
carbamoyl phosphate synthetase I
-
-
carbamoyl phosphate synthetase I
-
-
carbamoyl phosphate synthetase I
P31327
-
carbamoyl phosphate synthetase I
H9ZVS7
-
carbamoyl phosphate synthetase I
-
-
carbamoyl phosphate synthetase I
Q3S2E9
-
carbamoyl phosphate synthetase-1
P31327
-
carbamoyl-phosphate synthetase
P31327
-
carbamoyl-phosphate synthetase
-
-
carbamoyl-phosphate synthetase 1
-
-
carbamoyl-phosphate synthetase 1
P31327
-
carbamoyl-phosphate synthetase 1
-
-
Carbamoyl-phosphate synthetase I
-
-
-
-
Carbamoyl-phosphate synthetase I
P31327
-
Carbamoylphosphate synthase
-
-
-
-
Carbamoylphosphate synthase (ammonia)
-
-
-
-
Carbamoylphosphate synthetase
-
-
Carbamoylphosphate synthetase (ammonia)
-
-
-
-
Carbamoylphosphate synthetase I
-
-
-
-
Carbamoylphosphate synthetase I
-
-
carbamoylphosphate synthetase-I
-
-
Carbamyl phosphate synthase I
-
-
-
-
carbamyl phosphate synthetase I
-
-
carbamyl phosphate synthetase I
P31327
-
carbamyl-phosphate synthetase I
-
-
Carbamylphosphate synthetase
-
-
-
-
carbamylphosphate synthetase 1
-
-
Carbamylphosphate synthetase I
-
-
-
-
Carbmoylphosphate synthetase
-
-
-
-
Carbon-dioxide-ammonia ligase
-
-
-
-
Carbonate kinase (phosphorylating)
-
-
-
-
CPS
P31327
-
CPS
-
-
CPS I
-
-
-
-
CPS I-like (ammonia- and N-acetyl-L-glutamate-dependent)
-
-
CPS-1
-
-
CPS1
-
-
CPS1
Q8C196
-
CPSase I
Q3S2E9
-
CPSI
P31327
-
CPSI
H9ZVS7
-
EC 2.7.2.5
-
-
formerly
-
mitochondrial carbamoylphosphate synthetase I
-
-
Msm_0361
A5UK38
locus name
p165
-
-
urea-specific CPS
P31327
-
CAS REGISTRY NUMBER
COMMENTARY
9026-23-7
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Frog
-
-
-
Manually annotated by BRENDA team
Texas tortoise
-
-
Manually annotated by BRENDA team
African American children
SwissProt
Manually annotated by BRENDA team
gene CPSI
SwissProt
Manually annotated by BRENDA team
gene CPSI
-
-
Manually annotated by BRENDA team
isoform CPS1
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
C57BL/6 mice
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
C57BL/6 mice
-
-
Manually annotated by BRENDA team
Argentine tree frog
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae LPL26
LPL26
-
-
Manually annotated by BRENDA team
newborn
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
carbamoyl phosphate synthetase 1 deficiency, CPS1D, is an autosomal recessive disorder of the urea cycle which causes hyperammonemia. Two forms of CPS1D are recognized: a lethal neonatal type and a less severe, delayed onset type, phenotype, overview
malfunction
-
deficiency of the urea cycle enzyme carbamylphosphate synthetase 1 causes hyperammonemia with a vast range of clinical severity from neonatal onset with early lethality to onset after age 40 with rare episodes of hyperammonemic confusion, phenotypes of patients heterozygous for two mutations of the CPS1 gene, overview
malfunction
P31327
single nucleotide polymorphisms in the gene encoding CPS1 are involved, together with mutations in other genes encoding for other enzymes, in the development of severe asthma by African American children, which show a higher rate of this disease compared to other ethnics, overview. A combination of four single nucleotide polymorphisms (SNPs) within GSNOR, adrenergic receptor beta 2, and carbamoyl phosphate synthetase-1 give a 70% predictive value for lack of response to therapy
malfunction
-
deficiency of carbamoyl phosphate synthetase I in human results in hyperammonemia ranging from neonatally lethal to environmentally induced adult-onset disease
metabolism
-
CPS1 catalyzes the initial step of the urea cycle for ammonia detoxification and disposal
metabolism
-
CPS1 is a key enzyme of the urea cycle that catalyzes condensation of ammonia with bicarbonate to form carbamoyl phosphate
metabolism
-
CPSI is the first urea cycle enzyme
metabolism
Mus musculus C57BL/6
-
CPS1 is a key enzyme of the urea cycle that catalyzes condensation of ammonia with bicarbonate to form carbamoyl phosphate
-
physiological function
-
CPSI is a key regulator of the urea cycle for ammonia detoxification in animals
physiological function
-
CPSI is a key regulator of the urea cycle for ammonia detoxification in animals, including humans
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 ATP + NH3 + CO2 + H2O
?
show the reaction diagram
-
-
-
-
-
2 ATP + NH3 + CO2 + H2O
?
show the reaction diagram
-
primary ammonia-detoxifying enzyme
-
-
-
2 ATP + NH3 + CO2 + H2O
?
show the reaction diagram
-
first enzyme involved in the biosynthesis of urea in the liver ureotelic animals
-
-
-
2 ATP + NH3 + CO2 + H2O
?
show the reaction diagram
-
enzyme of urea cycle
-
-
-
2 ATP + NH3 + CO2 + H2O
?
show the reaction diagram
-
plays a key role in the regulation of the urea cycle
-
-
-
2 ATP + NH3 + CO2 + H2O
?
show the reaction diagram
-
enzyme is involved in arginine and urea synthesis
-
-
-
2 ATP + NH3 + CO2 + H2O
2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
2 ATP + NH3 + CO2 + H2O
2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
2 ATP + NH3 + CO2 + H2O
2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
-
2 ATP + NH3 + CO2 + H2O
2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
2 ATP + NH3 + CO2 + H2O
2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
Mus musculus C57BL/6
-
-
-
-
?
ATP + carbamate
ADP + carbamoyl phosphate
show the reaction diagram
-
-
-
r
ATP + carbamate
ADP + carbamoyl phosphate
show the reaction diagram
-
-
-
r
ATP + carbamate
ADP + carbamoyl phosphate
show the reaction diagram
Q9UWF8
-
-
r
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
Saccharomyces cerevisiae, Saccharomyces cerevisiae LPL26
-
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
ir
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
ir
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
ir
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
three step reaction
-
ir
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
Q9UWF8
three step reaction
-
ir
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
enzyme of the urea cycle
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
first step of the both the urea cycle and pyrimidine nucleotide biosynthesis patways
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
the enzyme T1405N genotype influences nitric oxide production as well as vascular smooth muscle reactivity
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
the first and rate-limiting step of the urea synthesis
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
CPS is the rate-determining enzyme of the urea cycle and catalyzes the conversion of ammonia and bicarbonate to carbamoylphosphate in the periportal and intermediate zones of a liver lobule, overview. The enzyme is responsible for ammonia elimination
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
CPS1 is a rate-limiting enzyme in the urea cycle
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
the product carbamoyl phosphate is used in the biosynthesis of pyrimidines, arginine, and urea
-
ir
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
the product carbamoylphosphate is used in the biosynethsis of pyrimidines, arginine, and urea
-
ir
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
?
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
?
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
Q3S2E9
-
-
-
?
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
no activity with Gln
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
no activity with Gln
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
no activity with Gln
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
no activity with Gln
-
-
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
H9ZVS7
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
-
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
-
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
A5UK38
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
Saccharomyces cerevisiae LPL26
-
-
-
?
ATP + NH4+ + HCO3- + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
P31327
-
-
-
?
ATP + NH4+ + HCO3- + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + NH4+ + HCO3- + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
Q8C196
-
-
-
?
ATP + NH4+ + HCO3- + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
the human enzyme removes excess, potentially neurotoxic ammonia via the urea cycle in a tightly regulated manner that avoids depletion of the ammonia pool, and shows inability to use glutamine as an alternative nitrogen donor
-
-
?
ATP + NH4+ + HCO3- + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
P31327
synthesis of carbamoyl phosphate requires coordination of two hCPS active sites with ATP cleavage occurring at duplicated ATP grasp domains B and C
-
-
?
additional information
?
-
-
this enzyme is unable to bind and utilize L-glutamine
-
?
additional information
?
-
-
polymorphism of carbamyl phosphate synthetase I, certain carbamyl phosphate synthetase I alleles are associated with clinical outcome
-
-
-
additional information
?
-
-
Rana cancrivora up-regulates hepatic carbamoyl phosphate synthetase I activity and tissue osmolyte levels in response to increased salinity
-
-
-
additional information
?
-
P31327
the enzyme might play an important role in spermiogenesis
-
-
-
additional information
?
-
-
severe hyperammonaemia and high mortality are observed in hCPS deficiency, a rare autosomal disease
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2 ATP + NH3 + CO2 + H2O
?
show the reaction diagram
-
-
-
-
-
2 ATP + NH3 + CO2 + H2O
?
show the reaction diagram
-
primary ammonia-detoxifying enzyme
-
-
-
2 ATP + NH3 + CO2 + H2O
?
show the reaction diagram
-
first enzyme involved in the biosynthesis of urea in the liver ureotelic animals
-
-
-
2 ATP + NH3 + CO2 + H2O
?
show the reaction diagram
-
enzyme of urea cycle
-
-
-
2 ATP + NH3 + CO2 + H2O
?
show the reaction diagram
-
plays a key role in the regulation of the urea cycle
-
-
-
2 ATP + NH3 + CO2 + H2O
?
show the reaction diagram
-
enzyme is involved in arginine and urea synthesis
-
-
-
2 ATP + NH3 + CO2 + H2O
2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
2 ATP + NH3 + CO2 + H2O
2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
2 ATP + NH3 + CO2 + H2O
2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
Mus musculus C57BL/6
-
-
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
enzyme of the urea cycle
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
first step of the both the urea cycle and pyrimidine nucleotide biosynthesis patways
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
the enzyme T1405N genotype influences nitric oxide production as well as vascular smooth muscle reactivity
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
the first and rate-limiting step of the urea synthesis
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
CPS is the rate-determining enzyme of the urea cycle and catalyzes the conversion of ammonia and bicarbonate to carbamoylphosphate in the periportal and intermediate zones of a liver lobule, overview. The enzyme is responsible for ammonia elimination
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
CPS1 is a rate-limiting enzyme in the urea cycle
-
-
?
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
the product carbamoyl phosphate is used in the biosynthesis of pyrimidines, arginine, and urea
-
ir
ATP + NH3 + CO2 + H2O
ADP + phosphate + carbamoylphosphate
show the reaction diagram
-
the product carbamoylphosphate is used in the biosynethsis of pyrimidines, arginine, and urea
-
ir
ATP + NH4+ + CO2 + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
H9ZVS7
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
A5UK38
-
-
-
?
ATP + NH4+ + HCO3- + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
P31327
-
-
-
?
ATP + NH4+ + HCO3- + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
Q8C196
-
-
-
?
ATP + NH4+ + HCO3- + H2O
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
the human enzyme removes excess, potentially neurotoxic ammonia via the urea cycle in a tightly regulated manner that avoids depletion of the ammonia pool, and shows inability to use glutamine as an alternative nitrogen donor
-
-
?
additional information
?
-
-
polymorphism of carbamyl phosphate synthetase I, certain carbamyl phosphate synthetase I alleles are associated with clinical outcome
-
-
-
additional information
?
-
-
Rana cancrivora up-regulates hepatic carbamoyl phosphate synthetase I activity and tissue osmolyte levels in response to increased salinity
-
-
-
additional information
?
-
P31327
the enzyme might play an important role in spermiogenesis
-
-
-
additional information
?
-
-
severe hyperammonaemia and high mortality are observed in hCPS deficiency, a rare autosomal disease
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
-
divalent metal ion required, Mg2+, Mn2+ or Co2+, Km for CoATP2-: 2.2 mM
Co2+
-
activates
Cs+
-
monovalent cation required, ATP hydrolysis is activated in the order of the series: Tl+, Cs+, Rb+, K+, Na+. Half-maximal activation at 1-2 mM
K+
-
monovalent cation required, ATP hydrolysis is activated in the order of the series: Tl+, Cs+, Rb+, K+, Na+. Half-maximal activation at 1-2 mM
Mg2+
-
divalent metal ion required, Mg2+, Mn2+ or Co2+, Km for MgATP2-: 1.35 mM
Mg2+
-
requirement for free Mg2+ in addition to the MgATP2- complex, inhibits above 20 mM
Mg2+
-
Mg2+ and Mn2+ are equally effective activators in the direction of carbamoyl phosphate synthesis, Km: 0.17 mM
Mg2+
-
free Mg2+ required for maximal activity
Mg2+
-
-
Mg2+
-
-
Mn2+
-
divalent metal ion required, Mg2+, Mn2+ or Co2+, Km for MnATP2-: 1.0 mM
Mn2+
-
can substitute for Mg2+ in activation, more effective on a molar basis, free Mn2+ at 5 mM and above inhibits
Mn2+
-
Mg2+ and Mn2+ are equally effective activators in the direction of carbamoyl phosphate synthesis. Excess Mn2+ inhibits
Na+
-
monovalent cation required, ATP hydrolysis is activated in the order of the series: Tl+, Cs+, Rb+, K+, Na+
Rb+
-
monovalent cation required, ATP hydrolysis is activated in the order of the series: Tl+, Cs+, Rb+, K+, Na+. Half-maximal activation at 1-2 mM
Tl+
-
monovalent cation required, ATP hydrolysis is activated in the order of the series: Tl+, Cs+, Rb+, K+, Na+. Half-maximal activation at 0.2-0.6 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-Amino-4-oxo-5-chloropentanoic acid
-
-
2-oxoglutarate
-
-
ADP
-
strong
alpha,beta-methyleneATP
-
-
AMP
-
1 mM, inhibition is more pronounced at 37C compared to 70C
Ca2+
-
binding of acetylglutamate to carbamoylphosphate synthetase is inhibited
Ca2+
-
the enzyme may be modulated in vivo by changes in the concentration of Ca2+ ions in the mitochondrial matrix
Ca2+
-
the inhibitory effect of free Ca2+ is weak. The calcium inhibition can be accounted for primarily by competitive interaction of CaATP2- at the second MgATP2- binding site. With 1 mM free Mg2+ and 5 mM MgATP2-, half-maximal inhibition is obtained with 0.2 mM CaATP2-
Carbamoyl phosphate
-
50% inhibition at 13 mM
cardiolipin
-
irreversible, inclusion of Mg2+ or MgATP2- in the incubation mixture prevent inactivation
citrate
-
-
CTP
-
0.3 mM, about 50% inhibition, inhibition is more pronounced at 37C compared to 70C
cytidine triphosphate
Q9UWF8
-
dCTP
-
1 mM, inhibition is more pronounced at 37C compared to 70C
dGTP
-
1 mM, inhibition is more pronounced at 37C compared to 70C
glycerol
-
in the presence of N-acetyl-L-glutamate the enzyme is inhibited by increasing concentrations of glycerol
HEPES
-
competitive with N-acetylglutamate
ITP
-
0.3 mM, about 50% inhibition, inhibition is more pronounced at 37C compared to 70C
malate
-
-
Mg2+
-
above 20 mM
Mn2+
-
at or above 5 mM
N-carbamoylglutamate
-
binding of acetylglutamate to carbamoylphosphate synthetase is inhibited
P1,P5-di-(adenosine-5')pentaphosphate
-
no inhibition by P1,P3-di-(adenosine-5')-pentaphosphate
palmitoyl-CoA
-
irreversible inactivation in a time- and concentration-dependent manner, this fatty acylation is specific for long-chain fatty acyl-CoA
peroxynitrite
Q8C196
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)
succinate
-
-
Tris
-
competitive with N-acetylglutamate
TTP
-
0.3 mM, about 50% inhibition, inhibition is more pronounced at 37C compared to 70C
UTP
-
0.3 mM, about 50% inhibition, inhibition is more pronounced at 37C compared to 70C
XTP
-
0.3 mM, about 50% inhibition, inhibition is more pronounced at 37C compared to 70C
Mn2+
-
activates
additional information
-
the urea cycle enzyme CPS1 is the antigen for Hep Par 1 antibody
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
acetylglutamate
-
acetylglutamate does not dissociate with each turnover of the enzyme; little activity at physiological concentrations of substrates in absence of acetylglutamate
acetylglutamate
-
activates; binding of acetylglutamate to carbamoylphosphate synthetase requires the presence of both Mg2+ and MgATP2-. The binding is inhibited by Ca2+ and N-carbamoylglutamate
acetylglutamate
-
N-acetyl-L-glutamate displaces the equilibrium towards monomer formation
acetylglutamate
-
no activity in absence of
acetylglutamate
-
activates; Km: 0.15 mM
acetylglutamate
-
activates; Km: 0.1 mM
acetylglutamate
-
activates; Km: 0.1 mM
acetylglutamate
-
allosteric activator
acetylglutamate
-
-
acetylglutamate
-
allosteric activator
acetylglutamate
-
not required as activator
acetylglutamate
-
activates; binding of acetylglutamate analogs, overview
dimethyl sulfoxide
-
activates in absence of the activator acetylglutamate
ethylene glycol
-
activates in absence of the activator acetylglutamate
glycerol
-
activates in absence of the activator acetylglutamate
glycerol
-
the recombinant enzyme CPS1 is activated by glycerol in the absence of N-acetyl-L-glutamate
inosine monophosphate
-
weak activator, the IMP binding site is located at the C-terminus, binding structure analysis from crystal structure with bound IMP, PDB ID 1CE8
N-acetyl-L-beta-phenylglutamate
-
lower activation of CPSI compared to N-acetyl-L-glutamate
N-acetyl-L-glutamate
-
-
N-acetyl-L-glutamate
-
i.e. NAG, allosteric activator, the binding mode and site in the crystal structure of human CPSI, PDB ID 2YVQ, is located in the C-terminal domain, docking experiments and structure, overview
N-acetyl-L-glutamate
-
i.e. NAG, allosteric activator, binding mode and site structure analysis by MALDI-TOF mass spectrometry, overview
N-acetyl-L-glutamate
-
i.e. NAG, dependent on the essential cofactor
N-acetyl-L-glutamate
Q8C196
nitration at Y1450 in an alpha-helix of allosteric domain prevents activation of CPS1 by N-acetyl-L-glutamate
N-acetyl-L-glutamate
-
essential activator
N-acetylglutamate
-
essential
N-acetylglutamate
-
the enzyme requires binding of and allosteric activation by N-acetylglutamate for catalytic activity
N-acetylglutamate
-
the enzyme requires allosteric activation by N-acetylglutamate
N-carbamoylglutamate
-
effective activator, Km: 2.0 mM
N-carbamyl-L-glutamate
-
-
ornithine
-
-
SIRT5
-
an NAD-dependent SIR2 deacetylase homologue, is involved in deacetylation and activation of carbamoyl phosphate synthetase 1, overview
-
SIRT5
-
a sirtuin enzyme, that deacetylates CPSI, which activates CPSI. During fasting, NAD in liver mitochondria increases, thereby triggering SIRT5 deacetylation of CPS1 and adaptation to the increase in amino acid catabolism. SIRT5 KO mice fail to up-regulate CPS1 activity and show elevated blood ammonia during fasting, overview
-
Sucrose
-
activates in absence of the activator acetylglutamate
L-alanine
-
infusion of alanine at 50% of resting energy expenditure for 36 h increases the enzyme activity more than twofold
additional information
-
not: UTP
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.39
ammonia
-
wild-type enzyme, comparison to native and mutant enzyme
0.0372
ATP
Q9UWF8
pH 8.0, deletion mutant lacking the last 13 residues of the carboxyl end
0.06
ATP
Q9UWF8
pH 8.0, recombinant enzyme
0.26
ATP
-
-
0.27
ATP
-
wild-type enzyme, comparison to native and mutant enzyme
0.43
ATP
-
mutant enzyme Y389C, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
0.45
ATP
-
mutant enzyme G1376S, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C; mutant enzyme T344A, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
0.47
ATP
-
recombinant wild type enzyme, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
0.55
ATP
-
pH 7.6, 37C, wild-type enzyme
0.57
ATP
-
mutant enzyme N355D, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
0.6 - 1
ATP
A5UK38
at pH 8.0 and 37C
0.62
ATP
-
mutant enzyme T1443A, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
0.68
ATP
-
pH 7.6, 37C, mutant T1406D
0.9
ATP
-
mutant enzyme A1378T, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
1.92
ATP
-
mutant enzyme T544M, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
2.3
CO2
-
NaHCO3, 37C, pH 8
7.2
CO2
-
NaHCO3, 70C, pH 7.5
2.2
CoATP2-
-
-
2.2
CoATP2-
-
HCO3-
1 - 4.5
HCO3-
A5UK38
at pH 8.0 and 37C
2.44
HCO3-
-
pH 7.6, 37C, wild-type enzyme
2.49
HCO3-
-
pH 7.6, 37C, mutant T1406D
3.6
HCO3-
-
mutant enzyme T1443A, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
4
HCO3-
-
recombinant wild type enzyme, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
4.2
HCO3-
-
mutant enzyme Y389C, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
4.3
HCO3-
-
mutant enzyme A1378T, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C; mutant enzyme T344A, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
4.5
HCO3-
-
mutant enzyme G1376S, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
4.6
HCO3-
-
mutant enzyme N355D, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
5
HCO3-
-
-
6.7
HCO3-
-
-
242
HCO3-
-
mutant enzyme T544M, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
0.054 - 0.11
MgATP2-
-
-
0.93
MgATP2-
-
-
1.1
MgATP2-
-
-
1.2
MgATP2-
-
-
1.35
MgATP2-
-
-
1
MnATP2-
-
-
0.29
N-acetylglutamate
-
pH 7.6, 37C, wild-type enzyme
0.44
N-acetylglutamate
-
pH 7.6, 37C, mutant T1406D
0.038
NH3
-
-
0.7
NH3
-
-
0.35
NH4+
-
pH 7.6, 37C, wild-type enzyme
0.58
NH4+
-
pH 7.6, 37C, mutant T1406D
0.8
NH4+
-
-
0.9
NH4+
-
mutant enzyme A1378T, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
1
NH4+
-
mutant enzyme N355D, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C; mutant enzyme T1443A, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C; recombinant wild type enzyme, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
1.1
NH4+
-
mutant enzyme G1376S, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C; mutant enzyme Y389C, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
1.2
NH4+
-
mutant enzyme T344A, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
1.3
NH4+
-
-
1.3
NH4+
-
mutant enzyme T544M, in 50 mM glycyl-glycine pH 7.4, 70 mM KCl, 1 mM dithiothreitol, 20 mM MgSO4, at 37C
15.6
NH4+
A5UK38
at pH 8.0 and 37C
1
MnATP2-
-
MgATP2-
additional information
additional information
-
kinetic parameters for utilization of ATP and ADP by mutant enzymes
-
additional information
additional information
-
kinetics of wild-type and mutant enzymes, overview. The Km of the enzyme for ammonia is 100fold lower than that for CPSs that also use glutamine, EC 6.3.5.5
-
additional information
additional information
-
kinetics, the Km of the enzyme for ammonia is 100fold lower than that for CPSs that also use glutamine, EC 6.3.5.5, kinetics for bicarbonate-dependent ATPase and carbamoyl phosphate-dependent ATP synthesis reactions, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.8
ammonia
-
wild-type enzyme, comparison to native and mutant enzyme
0.043
ATP
A5UK38
at pH 8.0 and 37C
2.4
ATP
-
wild-type enzyme, comparison to native and mutant enzyme
5.54
NH3
-
pH 7.6, 37C, mutant T1406D
5.73
NH3
-
pH 7.6, 37C, wild-type enzyme
0.052
NH4+
A5UK38
at pH 8.0 and 37C
0.044
HCO3-
A5UK38
at pH 8.0 and 37C
additional information
additional information
-
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0705
ATP
A5UK38
at pH 8.0 and 37C
4
0.003
HCO3-
A5UK38
at pH 8.0 and 37C
195
0.0033
NH4+
A5UK38
at pH 8.0 and 37C
54
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
13
Carbamoyl phosphate
-
-
0.015
palmitoyl-CoA
-
pH 7.6, 25C, substrate: MgATP2-
0.018
palmitoyl-CoA
-
pH 7.6, 25C, substrate: ammonia
0.024
palmitoyl-CoA
-
pH 7.6, 25C, substrate: HCO3-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00452
A5UK38
ATP synthetase reverse reaction rate, at pH 8.0 and 37C
0.014
Q9UWF8
recombinant enzyme expressed in Schizosaccharomyces pombe
0.077
A5UK38
carbamoyl phosphate synthetase reaction rate, at pH 8.0 and 37C
0.12
Q9UWF8
deletion mutant lacking the last 13 residues of the carboxyl end
0.3 - 0.46
-
-
0.4
Q9UWF8
recombinant enzyme expressed in Escherischia coli
0.43
-
purified recombinant tagged mutant C1327A
0.47
-
purified recombinant tagged mutant C1337A
0.86
-
purified recombinant tagged wild-type enzyme
16
-
value at 37C and 60C
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.8 - 7.6
-
-
7.6 - 8.6
-
at 37C
7.6
-
at 60C
7.6
P31327
assay at
7.8 - 8
-
at 37C
7.8
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.7 - 8.5
-
pH 5.7: about 60% of maximal activit, pH 8.5: about 80% of maximal activity, 70C
6.3 - 8
-
50% of maximal activity at pH 6.3 and 8.0
7 - 10
-
pH 7.0: about 60% of maximal activity, pH 10.0: about 60% of maximal activity, 37C
7 - 8.5
-
50% of maximal activity at pH 7.0 and 8.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 30
-
assay at
37
-
assay at
additional information
Q9UWF8
grows optimally at temperatures around 100C
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.6
A5UK38
calculated from amino acid sequence
4.7
-
isoelectric focusing
6.3
-
sequence calculation
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
hepatocarcinoma cell line, suppression of CPS1 expression occurs at the transcriptional level
Manually annotated by BRENDA team
P31327
cultured human primary hepatocytes, express CPS1 at abundant levels
Manually annotated by BRENDA team
-
hepatoid tumors of gastric and yolk sac
Manually annotated by BRENDA team
-
hepatocarcinoma cell line, suppression of CPS1 expression occurs at the transcriptional level
Manually annotated by BRENDA team
-
hepatocarcinoma cell line, suppression of CPS1 expression occurs at the transcriptional level
Manually annotated by BRENDA team
-
dynamic expression pattern of the enzyme in hepatocytes of different zones of the liver lobule, overview
Manually annotated by BRENDA team
-
expressed at higher level in adult testis than in fetal testis
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
additional information
-
mechanism underlying metabolic zonation, overview
Manually annotated by BRENDA team
additional information
-
no expression in gallbladder, thyroid, spleen, kidney, and skin, immunohistochemic analysis, overview, CPS1 expression is suppressed at the transcriptional level in human hepatocellular carcinoma cell lines
Manually annotated by BRENDA team
additional information
P31327
hepatocellular carcinoma cell lines Huh7, Huh7.5 and LH86 lack expression of CPS1. CPS1 is silenced or down-regulated in liver tumor tissues compared with the matched noncancerous tissues
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
contained completely within the inner mitochondrial membrane
Manually annotated by BRENDA team
-
constitutes 22-26% of the total matrix protein
Manually annotated by BRENDA team
-
15-20% of the total mitochondrial protein
Manually annotated by BRENDA team
-
the N-terminal targeting signal normally directs the nuclear-encoded protein to the mitochondrial matrix and is cleaved as the protein enters the matrix
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
34360
Q9UWF8
-
651213
50700
-
gel filtration
722163
78000 - 80000
-
native PAGE, gel filtration
1473
91000
A5UK38
gel filtration
728172
140000
-
gel filtration
674389
160000 - 251000
-
sedimentation velocity measurement, gel filtration, MW depends on protein concentration and composition of solvent
1456
165000 - 178000
-
gel filtration, density gradient centrifugation
1463
165000
-
-
652202
166000
-
mass spectrometry
693935
188000
-
gel filtration
1474
190000
-
gel filtration
1464
192000
-
recombinant enzyme, gel filtration
727610
202000
-
native enzyme, gel filtration
727610
222000
-
glycerol or sucrose density gradient centrifugation
1456
250000
-
gel filtration
1470
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 160000, SDS-PAGE
?
H9ZVS7
x * 163700, calculated from amino acid sequence
dimer
-
2 * 165000, SDS-PAGE of carboxymethylated enzyme
dimer
-
2 * 120000, SDS-PAGE
dimer
-
1 * 130000 + 1 * 55000, SDS-PAGE
dimer
-
2 * 32000, SDS-PAGE
homodimer
A5UK38
2 * 44000, SDS-PAGE, 2 * 41403, calculated from amino acid sequence
homodimer
-
2 * 41403, calculated from amino acid sequence
monomer
-
1 * 160000, SDS-PAGE in presence of a reducing agent
monomer
-
1 * 160000, sedimentation velocity measurement in presence of acetylglutamate alone, enzyme exists in a rapid, reversible monomer-dimer equilibrium. In presence of all substrates the enzyme exists as a monomer. The activator N-acetyl-L-glutamate displaces the equilibrium towards monomer formation
monomer
-
1 * 158000, sedimentation equilibrium in 6 M guanidine hydrochloride containing DTT, predominantly exists in the monomeric form
monomer
-
1 * 155000-167000, SDS-PAGE, gel filtration in guanidinium-Cl or in dodecyl sulfate
monomer
-
1 * 165000, SDS-PAGE
monomer
-
1 * 46600, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
acetylation
Mus musculus C57BL/6
-
mitochondrial CPSI is acetylated, and activated by deacetylation through SIRT5, overview
-
acetylation
-
mitochondrial CPSI is acetylated, and activated by deacetylation through SIRT5, overview
additional information
-
deacetylation by SIRT5 activates CPSI
lipoprotein
-
the enzyme becomes spontaneously palmitoylated, in a reversible manner depending on the palmitoyl-CoA concentrations, on an active site cysteine residue regulating the enzyme activity through inhibition, and for membrane attachment
additional information
-
the neutral sugar content is less than 0.5% of the total protein, or less than 4 residues/165000 molecular weight chain
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
1.5 A resolution structure of recombinant enzyme
-
recombinant enzyme
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
23
-
24 h, 20% v/v glycerol, 2 mM DTT, 13% loss of activity; 24 h, 20% v/v glycerol, 2 mM DTT, stable
1456
37
-
4 h, 30% loss of activity
1463
38.5
-
transition temperature
1474
46
-
5 min, 25% loss of activity
1463
55
-
5 min, 80% loss of activity
1463
60
-
extreme thermostable
642230
95
-
3 h, 50% loss of activity
1473
95
-
3 h, 50% loss of activity
722163
100
-
1 h, 50% loss of activity
1473
additional information
-
the enzyme is extreme thermostable
642229
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
no inactivation by elastase
Frog
-
elastase inactivates. Addition of ATP, Mg2+, K+ and N-acetyl-L-glutamate protects entirely
-
stabilty under pressure, progressive inactivation down to 50% of initial activity at 200 MPa, this residual activity is constant at 200 MPa for at least 50 min
-
acetylglutamate ATP accelerates the oxidative inactivation by mixtures of Fe3+, ascorbate, and O2
-
elastase inactivates. Addition of ATP, Mg2+, K+ and N-acetyl-L-glutamate protects entirely. Acetylglutamate alone speeds inactivation
-
glycerol and DTT stabilize during purification
-
inactivated by the Fe3+-oxygen-ascorbate model system for mixed-function oxidation. The susceptibility is markedly increased by acetylglutamate, when ATP is absent. ATP, and even more a mixture of ATP and bicarbonate protect from inactivation
-
trypsin, chymotrypsin, and papain also hydrolyze the oxidized enzyme considerybly faster than the native enzyme
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, stable for at least 1 month
-
4C, 6 months, stable
-
4C, 20% v/v glycerol, 0.1 or 2 mM DTT, 48 h, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
HisTrap column chromatography
-
Ni2+ affinity column chromatography, and gel filtration
A5UK38
recombinant enzyme
-
Kunitz-type soybean trypsin inhibitor-coupled Sepharose CL-4B column chromatography, Sephacryl S-200 gel filtration, and Superdex 200 FPLC gel filtration
-
native enzyme partially by mitochondria preparation and anion exchange chromatography
-
recombinant His6-tagged wild-type and mutant CPSIs from Spodoptera frugiperda SF9 cells by affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli DH10Bac cells
-
gene CPS1 is located on chromosome 2q35, genotyping and cloning of wild-type and mutant CPSIs in Cos7 and HeLa cells, which show increased activity with the wild-type gene, overview
-
gene CPS1, located on chromosome 2, genotyping, overview
P31327
gene CPSI, DNA and amino acid sequence determination and analysis, expression of the N-terminally His6-FLAG-tagged enzyme and mutant T1406D in Schizosaccharomyces pombe from pESP5, expression of mature protein of 1462 amino acid residues with the first 39 amino acids of the precursor protein replaced by a methionyl residue
-
gene CPSI, expression of the N-terminally His6-FLAG-tagged enzyme in Schizosaccharomyces pombe from pESP5
-
expressed in Escherichia coli BL21(DE3) cells
A5UK38
expression in Escherichia coli and Schizosaccharomyces pombe
Q9UWF8
expression in Escherichia coli
-
expression in Saccharomyces pombe
-
cloning of N-terminally His6-tagged wild-type and mutant CPSIs in Escherichia coli and expression in Spodopetra frugiperda SF9 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
human hepatocellular carcinoma cells do not express CPS1, whereas cultured human primary hepatocytes express abundant levels. CPS1 is silenced or down-regulated in liver tumor tissues compared with the matched noncancerous tissues. The expression of CPS1 in human hepatocellular carcinoma cells is restored with demethylation agent, 5-azacytidine. Two CpG dinucleotides, located near the transcription start site, and a CpG-rich region in the first intron are hypermethylated in human hepatocellular carcinoma cells
P31327
nutrient depletion does not increase CPS1 protein levels in wild-type or KO cells
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A1378T
-
the carbamoyl-phosphate synthetase deficiency-causing mutation greatly decreases enzyme activity
A438P
-
inactive
Al38P
-
the carbamoyl-phosphate synthetase deficiency-causing mutation greatly decreases enzyme activity
C1327A
-
the mutant shows reduced activity compared to the wild-type enzyme, the mutation significantly alters activity at the domain C ATP site, binding of N-acetylglutamate is affected, overview
C1337A
-
the mutant shows reduced activity compared to the wild-type enzyme, the mutation significantly alters activity at the domain C ATP site, binding of N-acetylglutamate is affected, overview
G1376S
-
the mutation has no detectable effect on activity
L1381S
-
the mutation is clearly disease-causing (carbamoyl-phosphate synthetase deficiency), since it induces strong enzyme instability
N355D
-
the carbamoyl-phosphate synthetase deficiency-causing mutation greatly decreases enzyme activity
R1262X
-
a premature stop codon mutation naturally occuring in carbamoyl phosphate synthetase 1 deficiency, CPS1D
R803G
-
naturally occuring missense mutation involved in carbamoyl phosphate synthetase 1 deficiency, CPS1D
T1405N
-
significant change in CPSI enzymatic function
T1406D
-
naturally occurring single nucleotide polymorphism, phenotype, overview
T1443A
-
the carbamoyl-phosphate synthetase deficiency-causing mutation greatly decreases enzyme activity
T344A
-
the mutation has no detectable effect on activity
T544M
-
the carbamoyl-phosphate synthetase deficiency-causing mutation greatly decreases enzyme activity
W1410K
-
site-directed mutagenesis, the mutant binds N-acetyl-L-beta-phenylglutamate at the N-acetyl-L-glutamate binding site
E261Q
-
no synthesis of carbonyl phosphate in presence of L-glutamine
K258L
-
synthesis of carbonyl phosphate in presence of L-glutamine
N1437D
-
site-directed mutagenesis, the mutant enzymes shows reduced activation by N-acetyl-L-glutamate compared to the wild-type enzyme
N1440D
-
site-directed mutagenesis, the mutant enzymes shows reduced activation by N-acetyl-L-glutamate compared to the wild-type enzyme
T1391V
-
site-directed mutagenesis, the mutant enzymes shows reduced activation by N-acetyl-L-glutamate compared to the wild-type enzyme
T1394A
-
site-directed mutagenesis, the mutant enzymes shows reduced activation by N-acetyl-L-glutamate compared to the wild-type enzyme
W1410K
-
site-directed mutagenesis, the mutant enzymes shows reduced activation by N-acetyl-L-glutamate compared to the wild-type enzyme
D265A
-
no carbamoyl phosphate synthesis
D265E
-
about 10% of the specific acitivity of the wild-type enzyme
D265N
-
about 10% of the specific acitivity of the wild-type enzyme
D810A
-
no carbamoyl phosphate synthesis
D810E
-
no carbamoyl phosphate synthesis
D810N
-
no carbamoyl phosphate synthesis
H262N
-
no carbamoyl phosphate synthesis
H807N
-
about 30% of the specific acitivity of the wild-type enzyme
I316G
-
about 10% of the specific acitivity of the wild-type enzyme
I316H
-
no carbamoyl phosphate synthesis
I316S
-
about 30% of the specific acitivity of the wild-type enzyme
L229G
-
about 30% of the specific acitivity of the wild-type enzyme
S228A
-
about 30% of the specific acitivity of the wild-type enzyme
D265A
Saccharomyces cerevisiae LPL26
-
no carbamoyl phosphate synthesis
-
D265N
Saccharomyces cerevisiae LPL26
-
about 10% of the specific acitivity of the wild-type enzyme
-
H262N
Saccharomyces cerevisiae LPL26
-
no carbamoyl phosphate synthesis
-
L229G
Saccharomyces cerevisiae LPL26
-
about 30% of the specific acitivity of the wild-type enzyme
-
S228A
Saccharomyces cerevisiae LPL26
-
about 30% of the specific acitivity of the wild-type enzyme
-
L390R
-
the mutation is clearly disease-causing (carbamoyl-phosphate synthetase deficiency), since it induces strong enzyme instability
additional information
-
connstruction of a domain A deleted mutant hCPS_DELTAA and functional characterization, the mutant shows slightly inccreased catalytic efficiency in absence of N-acetylglutamate and a 4fold increased Km for N-acetylglutamate compared to the wild-type enzyme
additional information
-
metabolic profiles of CPSI heterozygous mutants, mutations are splice site mutation c.4101 + 2T - C and c.3558 + 1G - C, overview
Y389C
-
the carbamoyl-phosphate synthetase deficiency-causing mutation greatly decreases enzyme activity
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
additional information
Mus musculus C57BL/6
-
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
-
additional information
Q9UWF8
construction of deletion mutant lacking the last 13 residues of the carboxyl end, 70% decrease of the enzyme activity in comparison of the full-length protein
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
P31327
human hepatocellular carcinoma cells do not express CPS1, whereas cultured human primary hepatocytes express abundant levels. CPS1 is silenced or down-regulated in liver tumor tissues compared with the matched noncancerous tissues. The expression of CPS1 in human hepatocellular carcinoma cells is restored with demethylation agent, 5-azacytidine. Two CpG dinucleotides, located near the transcription start site, and a CpG-rich region in the first intron are hypermethylated in human hepatocellular carcinoma cells
biotechnology
-
ammonia elimination as functional marker in hepatocyte cultivation and zonation in a bioreactor, and construction of a bioartificial liver, overview