INHIBITION OF OXIDATIVE-PHOSPHORYLATION BY PALMITOYL-COA IN DIGITONIN-PERMEABILIZED FIBROBLASTS - IMPLICATIONS FOR LONG-CHAIN FATTY-ACID BETA-OXIDATION DISORDERS

Long-chain fatty acid oxidation deficient patients present early in li fe with more severe features than patients with a medium-chain fatty a cid oxidation deficiency. This may be related to the more toxic effect of long-chain fatty acid derivatives. In this paper we have studied t he effect of different acyl-CoA esters, and palmitoyl-CoA in particula r, on succinate-driven oxidative phosphorylation, using digitonin perm eabilized human fibroblasts. Palmitoyl-CoA was found to inhibit the su ccinate-driven oxidative phosphorylation in a concentration dependent manner. If the inhibition of the oxidative phosphorylation system is a lso expressed under in vivo conditions this might explain some of the abnormalities found in patients with defects in long-chain fatty acid beta-oxidation.