Inhibition of hepatic Carnitine Palmitoyl-Transferase I (CPT IA) by Valproyl–CoA as a possible mechanism of Valproate-induced steatosis
Résumé
Carnitine palmitoyl-transferase I (CPT I) catalyses the synthesis of long-chain(LC)-acylcarnitines from LC-acyl-CoA esters. It is the rate-limiting enzyme of mitochondrial fatty acid β–oxidation (FAO) pathway and its activity is regulated by malonyl-CoA. The antiepileptic drug valproic acid (VPA) is a branched chain fatty acid that is activated to the respective CoA ester in the intra- and extra-mitochondrial compartments. This drug has been associated with a clear inhibition of mitochondrial FAO, which motivated our study on its potential effect on hepatic CPT I.
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