Medium-chain acyl-CoA dehydrogenase (MCAD) (MCAD)

Medium-chain acyl-CoA dehydrogenase (MCAD) is a key mitochondrial enzyme responsible for the initial step in the β-oxidation of fatty acids with chain lengths between 6 and 12 carbons. Primarily active in the liver, it facilitates the conversion of acyl-CoA to trans-2-enoyl-CoA, a process vital for generating energy and ketone bodies during fasting or metabolic stress [1, 2]. The enzyme is a member of the acyl-CoA dehydrogenase family and requires flavin adenine dinucleotide (FAD) as a cofactor for its catalytic activity [1]. Clinical significance arises primarily from MCAD deficiency, an autosomal recessive disorder that prevents the body from properly breaking down medium-chain fats, resulting in severe hypoglycemia and potential lethality if untreated [2, 4]. In drug development, MCAD is a target of interest for metabolic diseases; for instance, PPAR-alpha agonists like fenofibrate upregulate its expression to improve lipid profiles and reduce hepatic steatosis [3]. Monitoring its activity and the levels of associated acylcarnitines serves as a critical diagnostic and therapeutic benchmark in metabolic medicine [2].

Other names

ACADMMedium-chain acyl-Coenzyme A dehydrogenaseMitochondrial medium-chain fatty acid beta-oxidation enzyme

Transcriptional upregulation via PPAR-alpha activation or direct enzymatic inhibition by specific metabolites.