Acyl-CoA dehydrogenase family
acyl-coa dehydrogenase family
Acyl-CoA dehydrogenases (ACADs) are a class of enzymes that function to catalyze the initial step in each cycle of fatty acid Î²-oxidation in the mitochondria of cells. Their action results in the introduction of a trans double-bond between C2 (Î±) and C3 (Î²) of the acyl-CoA thioester substrate. Flavin adenine dinucleotide ( FAD ) is a required co-factor in addition to the presence of an active site glutamate in order for the enzyme to function.  ACADs can be categorized into three distinct groups based on their specificity for short-, medium-, or long-chain fatty acid acyl-CoA substrates. While different dehydrogenases target fatty acids of varying chain length, all types of ACADs are mechanistically similar. Differences in the enzyme occur based on the location of the active site along the amino acid sequence.   ACADs are an important class of enzymes in mammalian cells because of their role in metabolizing fatty acids present in ingested food materials. This enzyme's action represents the first step in fatty acid metabolism (the process of breaking long chains of fatty acids into acetyl CoA molecules). Deficiencies in these enzymes are linked to genetic disorders involving fatty acid oxidation (i.e. metabolic disorders).   ACAD enzymes have been identified in animals (of which there are 9 major eukaryotic classes), as well as plants, nematodes, fungi, and bacteria. Five of these nine classes are involved in fatty acid Î²-oxidation (SCAD, MCAD, LCAD, VLCAD, and VLCAD2), and the other four are involved in branched chain amino acid metabolism (i3VD, i2VD, GD, and iBD). Most acyl-CoA dehydrogenases are Î± 4 homotetramers, and in two cases (for very long chain fatty acid substrates) they are Î± 2 homodimers. An additional class of acyl-CoA dehydrogenase was discovered that catalyzes Î±,Î²-unsaturation reactions with steroid-CoA thioesters in certain types of bacteria. This class of ACAD was demonstrated to form Î± 2 Î² 2 heterotetramers, rather than the usual Î± 4 homotetramer, a protein architecture that evolved in order to accommodate a much larger steroid-CoA substrate.   ACADs are classified as EC 1.3.99.3.