Acyl-CoA dehydrogenase

Function

Acyl-CoA dehydrogenase (ACDH) catalyzes the introduction of a double bond between C2 and C3 of the thio-ester CoA substrate. This is the first reaction in fatty acid metabolism which produces acetyl-CoA. FAD is the cofactor of ACDH activity. ACDH is classified according to the length of its substrates as short- (SCAD), medium- (MCAD), very- and very long-chain (VLCAD) ACDH. MCAD can bind a broad range of chain length acyl-CoA substrates.

Disease

Impairment of the activity of ACDH causes a variety of diseases associated with lack of fatty acid metabolism. MCAD mutations are associated with Sudden Infant Death. SCAD deficiency is a recessive disorder of fatty acid β-oxidation.

Structural highlights

SCAD is a homodimer with a single FAD binding site. MCAD is a homotetramer with 4 FAD binding sites in the subunits interface and 4 binding sites for acyl-CoA substrate within each monomer. The rat CoA binding site is shown.