Cloning of a cDNA for Short/Branched Chain Acyl-Coenzyme A Dehydrogenase from Rat and Characterization of Its Tissue Expression and Substrate Specificity (original) (raw)

1996, Archives of Biochemistry and Biophysics

The acyl-CoA dehydrogenases (ACDs) 3 are a family The acyl-CoA dehydrogenases are a family of re-of related enzymes which catalyze the a,b-dehydrogelated enzymes which catalyze the a,b-dehydrogena-nation of acyl-CoA esters, transferring electrons to election of acyl-CoA esters, transferring electrons to tron-transferring flavoprotein [ETF, (1-6)]. Deficiencelectron-transferring flavoprotein. A cDNA for huies of these enzymes are important causes of human man short/branched chain acyl-CoA dehydrogenase disease (7, 8). Biochemical and immunological studies has recently been cloned, and it has been suggested have identified at least six distinct members of this that this enzyme represents the human homolog for enzyme family, each with a narrow substrate specificity the previously reported 2-methyl branched chain (2-5, 9, 10). Very long, long, medium, and short chain acyl-CoA dehydrogenase purified from rat liver. We acyl-CoA dehydrogenases (VLCAD, LCAD, MCAD, and now report the cloning and expression of rat short/ SCAD) catalyze the first step in the b-oxidation of branched chain acyl-CoA dehydrogenase and charstraight chain fatty acids with substrate optima of acterization of its substrate specificity. The rat en-16, 16, 8, and 4 carbons, respectively (2, 5, 9, 10). zyme is more active toward longer carbon side Isovaleryl-CoA dehydrogenase (IVD) and a 2-methyl chains than its human counterpart, while the human branched chain acyl-CoA dehydrogenase (2-meBCAD) enzyme can utilize substrates with longer primary catalyze the third step in leucine and isoleucine/valine carbon chains. In addition, short/branched chain metabolism, respectively (2-4). A purified rat 2-meBacyl-CoA dehydrogenase can utilize valproyl-CoA as CAD has been shown to have 8.4% activity with vala substrate. Northern blotting of mRNA shows ubiqproyl-CoA compared with its optimum substrate (S)-2uitous tissue expression of both the rat and human methylbutyryl-CoA (11). We have recently cloned and enzyme. Further study of these enzymes will be helpcharacterized a cDNA for human short/branched chain ful in understanding structure/function relationacyl-CoA dehydrogenase (SBCAD) and have suggested ships in this gene family.