Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:6.3.5.5 (
CPS
)
1,262
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Regulation of mitochondrial carbamoyl-phosphate synthetase 1 activity by active site fatty acylation. 1157 71
