Medium-chain specific acyl-CoA dehydrogenase, mitochondrial

Medium-chain specific acyl-CoA dehydrogenase (MCAD) is a mitochondrial enzyme that catalyzes the first step of fatty acid beta-oxidation, converting medium-chain fatty acyl-CoA thioesters (6–12 carbons, extending to C14–C16) into enoyl-CoA and transferring electrons to the respiratory chain via ETF and ETF-ubiquinone oxidoreductase (UniProt: P11310). This process is essential for energy production from fats in mitochondria.

MCAD is located in the inner mitochondrial membrane and participates in cellular energy metabolism. Genetic deficiency of ACADM causes acyl-CoA dehydrogenase medium-chain deficiency (ACADMD, MIM 201450), a severe inborn error presenting with fasting hypoglycemia, hepatic dysfunction, and encephalopathy often fatal in infancy (UniProt: P11310).

In Alzheimer's Disease, MCAD shows disease-relevant elevation: the protein is upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of +0.48 across subcellular fractions (Chaparral AD proteomics). This increase may reflect altered mitochondrial energy metabolism or compensatory responses to metabolic stress in AD pathology.