RGD Reference Report - Regulation of mitochondrial carbamoyl-phosphate synthetase 1 activity by active site fatty acylation. - Rat Genome Database

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Regulation of mitochondrial carbamoyl-phosphate synthetase 1 activity by active site fatty acylation.

Authors: Corvi, MM  Soltys, CL  Berthiaume, LG 
Citation: Corvi MM, etal., J Biol Chem. 2001 Dec 7;276(49):45704-12. Epub 2001 Sep 27.
RGD ID: 2303524
Pubmed: PMID:11577071   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M102766200   (Journal Full-text)

In addition to its role in reversible membrane localization of signal-transducing proteins, protein fatty acylation could play a role in the regulation of mitochondrial metabolism. Previous studies have shown that several acylated proteins exist in mitochondria isolated from COS-7 cells and rat liver. Here, a prominent fatty-acylated 165-kDa protein from rat liver mitochondria was identified as carbamoyl-phosphate synthetase 1 (CPS 1). Covalently attached palmitate was linked to CPS 1 via a thioester bond resulting in an inhibition of CPS 1 activity at physiological concentrations of palmitoyl-CoA. This inhibition corresponds to irreversible inactivation of CPS 1 and occurred in a time- and concentration-dependent manner. Fatty acylation of CPS 1 was prevented by preincubation with N-ethylmaleimide and 5'-p-fluorosulfonylbenzoyladenosine, an ATP analog that reacts with CPS 1 active site cysteine residues. Our results suggest that fatty acylation of CPS 1 is specific for long-chain fatty acyl-CoA and very likely occurs on at least one of the essential cysteine residues inhibiting the catalytic activity of CPS 1. Inhibition of CPS 1 by long-chain fatty acyl-CoAs could reduce amino acid degradation and urea secretion, thereby contributing to nitrogen sparing during starvation.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ATP binding  IDA 2303524 RGD 
carbamoyl-phosphate synthase (ammonia) activity  IDA 2303524 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cps1  (carbamoyl-phosphate synthase 1)


Additional Information