Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (MCAD)

Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (MCAD), is a mitochondrial enzyme crucial for fatty acid β-oxidation, catalyzing the initial dehydrogenation step of fatty acids with chain lengths of 6 to 12 carbons. It is encoded by the ACADM gene and functions as a homotetramer that converts medium-chain fatty acyl-CoAs into their corresponding trans-2-enoyl-CoAs, enabling subsequent steps in energy production from fat. The enzyme operates in tissues with high metabolic demands, notably liver, heart, and muscle, and its activity is especially critical during periods of fasting when energy reserves must be mobilized. Genetic defects in MCAD cause MCADD, a common metabolic disorder marked by inability to efficiently process medium-chain fats, resulting in hypoglycemia, encephalopathy, and, if untreated, sudden infant death. MCAD also has emerging implications in certain cancers, supporting mitochondrial function and energy production in proliferating tumor cells[1][2][3][4][5][6].

Other names

Medium chain acyl-CoA dehydrogenaseMedium-chain acyl-CoA dehydrogenaseMCADHAcyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chainEC 1.3.8.7ACADM (gene/protein)

Catalyzes the first step in mitochondrial β-oxidation of medium-chain fatty acids (removes hydrogen from C-2 and C-3 to form trans-2-enoyl-CoA, then transfers electrons to electron transfer flavoprotein, ETF)[1][2][5]. Inhibition or loss leads to toxic accumulation of medium-chain fatty acids and energy deficiency.