L-carnitine stimulation of mitochondrial oxidative phosphorylation rate in isolated rat skeletal muscle mitochondria.
L-carnitine effects on mitochondrial adenosine triphosphate (ATP) production rate were investigated in mitochondria isolated from rat extensor digitorum longus (EDL) muscle. Kinetic parameters, apparent Michaelis constant for free adenosine diphosphate (ADP) (K(m)) and apparent maximal ATP production rate (Vmax), were determined in absence and presence of L-carnitine. Although the K(m) remained unchanged in response to L-carnitine addition when pyruvate + malate was oxidized, the affinity of isolated mitochondria towards ADP was decreased when pyruvate + palmitoylcarnitine + malate was used as substrate. As a result of L-carnitine addition, a slight non-significant (P < 0.07) increase in Vmax was observed with pyruvate + malate while the increase reached the level of significance with pyruvate + palmitoylcarnitine + malate. Moreover, a positive correlation was obtained when mitochondrial ATP production rate was plotted against the difference between values measured with and without L-carnitine. Our data suggest that addition of L-carnitine to isolated rat skeletal muscle mitochondria can stimulate mitochondrial oxidative phosphorylation rate under conditions where the inhibitory effect of acetyl-CoA accumulation on pyruvate dehydrogenase complex activity is optimized. A change in the control of mitochondrial ATP flux by pyruvate dehydrogenase (PDH) complex might also occur with increasing mitochondrial ATP production rate, reinforcing the L-carnitine effects.
Berthon
P
P
Laboratoire de Physiologie-GIP Exercice, Faculté de Médecine Jacques Lisfranc, Université Jean Monnet, Saint-Etienne, France.
Van der Veer
M
M
Denis
C
C
Freyssenet
D
D
D000255:Adenosine Triphosphate / Q000493:pharmacokinetics; D000818:Animals; D002331:Carnitine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000255:Adenosine Triphosphate; D002331:Carnitine