Very long-chain acyl-CoA dehydrogenase, mitochondrial

Very long-chain acyl-CoA dehydrogenase (VLCAD), encoded by ACADVL, is a mitochondrial enzyme that catalyzes the first step of fatty acid beta-oxidation (UniProt: P49748). It specifically acts on saturated fatty acyl-CoAs with 12–24 carbon chains, transferring electrons to electron transfer flavoprotein to generate trans-2-enoyl-CoA and support cellular energy production from fats (UniProt: P49748).

VLCAD is expressed in mitochondria and its dysfunction is associated with acyl-CoA dehydrogenase very long-chain deficiency (ACADVLD; MIM 201475), an inborn error of metabolism characterized by impaired long-chain fatty acid oxidation and heterogeneous clinical presentations ranging from severe childhood cardiomyopathy to adult-onset myopathy (UniProt: P49748).

In Alzheimer's disease, VLCAD is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log₂ fold-change of 0.40 across analyzed subcellular fractions (Chaparral AD proteomics). This upregulation may reflect altered mitochondrial energy metabolism in AD pathology, though the functional significance remains to be determined.