L-CARNITINE STIMULATION OF MITOCHONDRIAL OXIDATIVE-PHOSPHORYLATION RATE IN ISOLATED RAT SKELETAL-MUSCLE MITOCHONDRIA

L-carnitine effects on mitochondrial adenosine triphosphate (ATP) prod uction rate were investigated in mitochondria isolated from rat extens or digitorum longus (EDL) muscle. Kinetic parameters, apparent Michael is constant for free adenosine diphosphate (ADP) (K-m) and apparent ma ximal ATP production rate (V-max), were determined in absence and pres ence of L carnitine. Although the K-m remained unchanged in response t o L-carnitine addition when pyruvate + malate was oxidized, the affini ty of isolated mitochondria towards ADP was decreased when pyruvate palmitoylcarnitine + malate was used as substrate. As a result of L-ca rnitine addition, a slight non-significant (P < 0.07) increase in V-ma x was observed with pyruvate + malate while the increase reached the l evel of significance with pyruvate + palmitoylcarnitine + malate. More over, a positive correlation was obtained when mitochondrial ATP produ ction rate was plotted against the difference between values measured with and without L-carnitine. Our data suggest that addition of L-carn itine to isolated rat skeletal muscle mitochondria can stimulate mitoc hondrial oxidative phosphorylation rate under conditions where the inh ibitory effect of acetyl-CoA accumulation on pyruvate dehydrogenase co mplex 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-carni tine effects. (C) 1997 Elsevier Science Inc.