New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle.
In skeletal muscle, carnitine plays an essential role in the translocation of long-chain fatty-acids into the mitochondrial matrix for subsequent beta-oxidation, and in the regulation of the mitochondrial acetyl-CoA/CoASH ratio. Interest in these vital metabolic roles of carnitine in skeletal muscle appears to have waned over the past 25 years. However, recent research has shed new light on the importance of carnitine as a regulator of muscle fuel selection. It has been established that muscle free carnitine availability may be limiting to fat oxidation during high intensity submaximal exercise. Furthermore, increasing muscle total carnitine content in resting healthy humans (via insulin-mediated stimulation of muscle carnitine transport) reduces muscle glycolysis, increases glycogen storage and is accompanied by an apparent increase in fat oxidation. By increasing muscle pyruvate dehydrogenase complex (PDC) activity and acetylcarnitine content at rest, it has also been established that PDC flux and acetyl group availability limits aerobic ATP re-synthesis at the onset of exercise (the acetyl group deficit). Thus, carnitine plays a vital role in the regulation of muscle fuel metabolism. The demonstration that its availability can be readily manipulated in humans, and impacts on physiological function, will result in renewed business and scientific interest in this compound.
Stephens
Francis B
FB
Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK. francis.stephens@nottingham.ac.uk
Constantin-Teodosiu
Dumitru
D
Greenhaff
Paul L
PL
D000108:Acetylcarnitine / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002331:Carnitine / Q000378:metabolism*; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology*; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D050356:Lipid Metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism
D011768:Pyruvate Dehydrogenase Complex; D000108:Acetylcarnitine; D006003:Glycogen; D002331:Carnitine