Human long chain, very long chain and medium chain acyl-CoA dehydrogenases are specific for the S-enantiomer of 2- methylpentadecanoyl-CoA.
The acyl-CoA dehydrogenases are a family of mitochondrial flavoenzymes involved in fatty acid and branched chain amino-acid metabolism. Long chain acyl-CoA dehydrogenase (LCAD) and short/branched chain acyl-CoA dehydrogenase (SBCAD) have been shown to have activity towards 2-methyl branched chain acyl-CoA substrates of varying chain lengths. In humans, long chain 2-branched chain fatty acids such as pristanic acid are largely thought to be metabolized in peroxisomes through desaturation of their CoA esters by branched chain acyl-CoA oxidase, but LCAD is also capable of utilizing 2-methyldecanoyl- and 2-methylpalmitoyl-CoA as substrate [1]. Since the acyl-CoA oxidase reaction is specific for the S-enantiomer of the branched chain substrates, we investigated the stereo specificity of mitochondrial LCAD. Purified LCAD had a specific activity of 390 and 340 mU/mg of purified LCAD protein using palmitoyl-CoA and S-2-methylpentadecanoyl-CoA, respectively, as substrate. No activity was measurable with R-2-methylpentadecanoyl-CoA. Purified medium chain acyl-CoA dehydrogenase (MCAD) could also utilize S-2-methylpentadecanoyl-CoA as a substrate, but not R-2-methylpentadecanoyl-CoA. These results indicate that LCAD and MCAD are specific for the S-enantiomers of methylbranched chain substrates. Crude mitochondrial extracts showed no activity when dehydrogenating activity was measured with R/S-2-methylpalmitoyl-CoA or S-2-methylpentadecanoyl-CoA after inactivation of the extract with antibodies to very long chain acyl-CoA dehydrogenase and MCAD, suggesting that this substrate is not useful in identifyig clinical deficiencies of LCAD.
Battaile
K P
KP
Mayo Clinic and Mayo Foundation, Department of Medical Genetics and Biochemistry/Molecular Biology, 200 First St, SW, Rochester, MN 55905, USA.
McBurney
M
M
Van Veldhoven
P P
PP
Vockley
J
J
D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D000937:Antigen-Antibody Reactions; D006801:Humans; D008931:Mitochondria, Muscle / Q000201:enzymology; D018482:Muscle, Skeletal / Q000201:enzymology*; D010171:Palmitoyl Coenzyme A / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
C111596:2-methylpentadecanoyl coenzyme A; D010171:Palmitoyl Coenzyme A; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain