Inhibition of camitine-acyl transferase I by oxfenicine studied in vivo with [11C]-labeled fatty acids

Methods: Anesthetized pigs were studied with [C-11]-labeled fatty acids (FAs) with carbon chain length ranging from 8 to 16 carbon atoms, during control conditions and during inhibition of carnitine-palmitoyl transferase I (CPT I) with oxfenicine. The myocardial uptake of [C-11]FAs from blood was measured together with the relative distribution of [C-11]-acyl-CoA between rapid mitochondrial oxidation and incorporation into slow turnover lipid pools in the heart. Results: During baseline conditions, the fractional oxidative utilization of palmitate was almost as high as that of carnitine-independent short-chain FAs, unless the carnitine shuttle was inhibited by high levels of lactate. Inhibition of CPT I almost completely blocked the oxidative pathway for palmitic acid and reduced the fractional oxidative utilization, while the rate of oxidative metabolism of acyl-CoA was unaffected. Conclusions: [C-11]-Labeled FAs allow rapid oxidation to be well separated from esterification into slow turnover lipid pools in the heart of anaesthetized pigs. The fractional oxidative utilization of [C-11]-palmitate serves well to characterize, in vivo, the carnitine-dependent transfer of long-chain FAs. (c) 2005 Elsevier Inc. All rights reserved.