Short-chain acyl-CoA dehydrogenase (SCAD)

Short-chain acyl-CoA dehydrogenase (SCAD) is a mitochondrial enzyme, encoded by the ACADS gene, responsible for catalyzing the initial dehydrogenation (oxidation) of short-chain fatty acyl-CoAs—specifically butyryl-CoA—in the process of fatty acid β-oxidation. SCAD functions as a homotetramer, each monomer binding flavin adenine dinucleotide (FAD) as a cofactor, and is essential for energy production from fatty acids, especially during fasting or periods of high energy demand. Deficiency of SCAD, also known as SCAD deficiency (SCADD), impairs fatty acid oxidation, leading to accumulation of butyrylcarnitine and ethylmalonic acid and presenting with metabolic, neuromuscular, or sometimes asymptomatic phenotypes. SCAD deficiency is inherited in an autosomal recessive manner, and its diagnosis relies on biochemical markers and genetic analysis. There are no classic therapeutics directly targeting SCAD, but supplementation with FAD may provide benefit in some deficiency cases [3][4][5][6][7][8].

Other names

butyryl-CoA dehydrogenasebutanoyl-CoA dehydrogenaseshort-chain acyl CoA dehydrogenaseunsaturated acyl-CoA reductase3-hydroxyacyl CoA reductaseethylene reductaseenoyl-coenzyme A reductaseunsaturated acyl coenzyme A reductasebutyryl coenzyme A dehydrogenaseACADS (gene)

Enzyme cofactor supplementation (FAD therapy) may restore function in deficient individuals [4] Null (no currently approved drugs modulate activity)