Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

6.3.5.5

Official Name

carbamoyl-phosphate synthase (glutamine-hydrolysing)

Name from literature

carbamoyl phosphate synthase

Pathway from literature

the de novo UTP biosynthetic pathway

Pathway from KEGG

Amino Acid Metabolism; Glutamate metabolism; map00251

Nucleotide Metabolism; Pyrimidine metabolism; map00240

Organisms

Human (9606)

Genome localization

2p22-p21[790 ],

Comments

The product carbamoyl phosphate is an intermediate in the biosynthesis of arginine and the pyrimidine nucleotides [4]. The enzyme from Escherichia coli has three separate active sites, which are connected by a molecular tunnel that is almost 100 A in length [8]. The amidotransferase domain within the small subunit of the enzyme hydrolyses glutamine to ammonia via a thioester intermediate. The ammonia migrates through the interior of the protein, where it reacts with carboxy phosphate to produce the carbamate intermediate. The carboxy-phosphate intermediate is formed by the phosphorylation of bicarbonate by ATP at a site contained within the N-terminal half of the large subunit. The carbamate intermediate is transported through the interior of the protein to a second site within the C-terminal half of the large subunit, where it is phosphorylated by another ATP to yield the final product, carbamoyl phosphate [6].

Rate-limiting Description

"Cytidine (10(-3) M) inhibited synthesis through the salvage pathway, but did not significantly alter induction of carbamyl phosphate synthetase II, the rate-limiting enzyme for the de novo pathway." (4361297)

"The rate-limiting step in de novo pyrimidine nucleotide synthesis is catalyzed by the carbamoyl phosphate synthetase II (CPSase) domain of CAD." (15326225)

"Recent studies demonstrate that CAD, a rate-limiting enzyme in the de novo synthesis of pyrimidines, is regulated through reversible phosphorylation, Myc-dependent transcriptional changes and caspase-mediated degradation." (12678497)

Regulatory Information

Upstream transcription factor

6667;3091

Regulatory type

Detail

transcriptional factor;HIF-1alpha(3091)

"cad gene expression is repressed by hypoxia-inducible factor-1alpha, which represents a functional link between hypoxia and cell-cycle arrest." (16155188)

transcriptional factor;Sp-1(6667)

"the cad gene is regulated by a nonclassical ERalpha/Sp1-mediated pathway." (12746293)

phosphorylation;

P27708

phosphorylation;

P27708:from_uniprot:1423_Phosphoserine

phosphorylation;

P27708:from_uniprot:1823_Phosphoserine

phosphorylation;

P27708:from_uniprot:1859_Phosphoserine

Gene ontology

Gene ontology

GO:0016597 (F) amino acid binding [P27708 ];
GO:0008270 (F) zinc ion binding [P27708 ];
GO:0004151 (F) dihydroorotase activity [P27708 ];
GO:0006207 (P) 'de novo' pyrimidine base biosynthetic process [P27708 ];
GO:0004088 (F) carbamoyl-phosphate synthase (glutamine-hyd... [P27708 ];
GO:0004070 (F) aspartate carbamoyltransferase activity [P27708 ];
GO:0005829 (C) cytosol [P27708 ];
GO:0006221 (P) pyrimidine nucleotide biosynthetic process [P27708 ];
GO:0005524 (F) ATP binding [P27708 ];
GO:0006541 (P) glutamine metabolic process [P27708 ];

Subcellular localization

Localization

cytoplasm [P27708 ];

Links

SwissProt

P27708

Entrez Gene

790

HPRD

06437



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  Last Modified: 2009-03-24  
  Design by Zhao Min