Control of lipid oxidation at the mitochondrial levelThis paper article is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

Abstract

The rate of lipid oxidation during exercise is controlled at several sites, and there is a reciprocal dependency between oxidation of lipids and carbohydrates (CHO). It is well known that the proportion of the 2 fuels oxidized is influenced by substrate availability and exercise intensity, but the mechanisms regulating fuel preferences remain unclear. During intense exercise, oxidation of long-chain fatty acids (LCFAs) decreases, and the major control is likely to be at the mitochondrial level. Potential mitochondrial sites for control of lipid oxidation include transport of LCFAs into mitochondrial matrix, β-oxidation, the tricarboxylic acid cycle, and the electron transport chain (ETC). CHO catabolism may impair lipid oxidation by interfering with the transfer of LCFAs into mitochondria and by competing for mutual cofactors (i.e., nicotinamide adenine dinucleotide and (or) coenzyme A (CoA)). The different effect of energy state on the catabolism of CHO and lipids is likely to be of major importance in explaining the shift in fuel utilization during intensive exercise. Formation of acetyl-CoA from CHO is activated by a low energy state, and will lead to accumulation of products that are inhibitory to lipid oxidation. In contrast, β-oxidation of LCFAs to acetyl-CoA is not stimulated by a low energy state. Further interaction between CHO and LCFAs may occur by substrate competition for electron carriers at ETC, due to provisions of electrons through different complexes. Feedback inhibition of β-oxidation by redox state is thought to be an important mechanism for the slowing of lipid oxidation during intensive exercise.