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PMID:11577071
| Citation |
Corvi, MM, Soltys, CL and Berthiaume, LG (2001) Regulation of mitochondrial carbamoyl-phosphate synthetase 1 activity by active site fatty acylation. J. Biol. Chem. 276:45704-12 |
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| Abstract |
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. |
| Links |
PubMed Online version:10.1074/jbc.M102766200 |
| Keywords |
Acylation; Animals; Binding Sites; Carbamoyl-Phosphate Synthase (Ammonia)/antagonists & inhibitors; Carbamoyl-Phosphate Synthase (Ammonia)/isolation & purification; Carbamoyl-Phosphate Synthase (Ammonia)/metabolism; Chromatography, Thin Layer; Ethylmaleimide/pharmacology; Fatty Acids/metabolism; Hydroxylamine/pharmacology; Kinetics; Liver/drug effects; Liver/enzymology; Liver/metabolism; Male; Mitochondria/enzymology; Palmitoyl Coenzyme A/metabolism; Rats; Rats, Sprague-Dawley; Submitochondrial Particles/enzymology; Submitochondrial Particles/metabolism; Substrate Specificity |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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