2,6-DIMETHYLHEPTANOYL-COA IS A SPECIFIC SUBSTRATE FOR LONG-CHAIN ACYL-COA DEHYDROGENASE (LCAD) - EVIDENCE FOR A MAJOR ROLE OF LCAD IN BRANCHED-CHAIN FATTY-ACID OXIDATION

Oxidation of straight-chain fatty acids in mitochondria involves the c omplicated interaction between a large variety of different enzymes. S o far four different mitochondrial straight-chain acyl-CoA dehydrogena ses have been identified. The physiological function of three of the f our acyl-CoA dehydrogenases has been resolved in recent years especial ly from studies on patients suffering from certain inborn errors of mi tochondrial fatty acid beta-oxidation. The physiological role of long- chain acyl-CoA dehydrogenase (LCAD) has remained obscure, however. The results described in this paper provide strong evidence suggesting th at LCAD plays a central role in branched-chain fatty acid metabolism s ince it turns out to be the major acyl-CoA dehydrogenase reacting with 2,6-dimethylheptanoyl-CoA, a metabolite of pristanic acid, which itse lf is the alpha-oxidation product of phytanic acid. (C) 1998 Elsevier Science B.V. All rights reserved.