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 complicated interaction between a large variety of different enzymes. So far four different mitochondrial straight-chain acyl-CoA dehydrogenases have been identified. The physiological function of three of the four acyl-CoA dehydrogenases has been resolved in recent years especially from studies on patients suffering from certain inborn errors of mitochondrial 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 that LCAD plays a central role in branched-chain fatty acid metabolism since it turns out to be the major acyl-CoA dehydrogenase reacting with 2,6-dimethylheptanoyl-CoA, a metabolite of pristanic acid, which itself is the alpha-oxidation product of phytanic acid.
Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. wanders@amc.uva.nl
R J
RJ
Wanders
S
S
Denis
J P
JP
Ruiter
L
L
IJlst
G
G
Dacremont
D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency / Q000378:metabolism*; D002478:Cells, Cultured; D003065:Coenzyme A / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D013379:Substrate Specificity
C114517:2,6-dimethylheptanoyl-CoA; D005227:Fatty Acids; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D044942:Acyl-CoA Dehydrogenase, Long-Chain; C038808:2-methylacyl-CoA dehydrogenase; D003065:Coenzyme A