Inhibition of hepatic Carnitine Palmitoyl-Transferase I (CPT IA) by Valproyl–CoA as a possible mechanism of Valproate-induced steatosis

Cátia C.P. Aires , Lodewijk Ijlst , Femke Stet , Carina Prip-Buus , Isabel Tavares De Almeida , Marinus Duran , Ronald J.A. Wanders , Margarida F.B. Silva

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.

Mots clés: CPT I; VPA; Δ-VPA; CoA; VP-CoA; Δ-VP-CoA; AC; LCFA; FAO; LC-FAO; BCA; ACN; HSA; C16-CoA; Mal-CoA; ESI-MS/MS; Carnitine Palmitoyl-transferase I; Valproic acid; Malonyl-CoA; Fatty acid oxidation; Drug induced hepatic steatosis

Cátia C.P. Aires, Lodewijk Ijlst, Femke Stet, Carina Prip-Buus, Isabel Tavares De Almeida, et al.. Inhibition of hepatic Carnitine Palmitoyl-Transferase I (CPT IA) by Valproyl–CoA as a possible mechanism of Valproate-induced steatosis. Biochemical Pharmacology, 2009, 79 (5), pp.792. ⟨10.1016/j.bcp.2009.10.011⟩. ⟨hal-00547637⟩