protein
Very long-chain acyl-CoA dehydrogenase, mitochondrial
aka VLCAD
Gene
ACADVL
Organism
Homo sapiens(9606)
Length
655 aa
Mass
70,390 Da
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.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
+0.445
S2
not detected
S3
+0.352
Mean log₂FC across detected fractions: +0.3981 (2 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Very long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation (FAO), breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (PubMed:17564966, PubMed:18227065, PubMed:7668252, PubMed:9461620, PubMed:9599005, PubMed:9839948). The first step of FAO consists in the proR-proR stereospecific alpha, beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physiologic electron acceptor, resulting in the formation of trans-2-enoyl-CoA ((2E)-enoyl-CoA) (PubMed:18227065, PubMed:7668252, PubMed:9461620, PubMed:9839948). Among the different mitochondrial acyl-CoA dehydrogenases, very long-chain specific acyl-CoA dehydrogenase acts specifically on fatty acyl-CoAs with saturated 12 to 24 carbons long primary chains (PubMed:17564966, PubMed:21237683, PubMed:9839948)
Disease associations
Acyl-CoA dehydrogenase very long-chain deficiencyACADVLD
An inborn error of mitochondrial fatty acid beta-oxidation which leads to impaired long-chain fatty acid beta-oxidation. It is clinically heterogeneous, with three major phenotypes: a severe childhood form characterized by early onset, high mortality and high incidence of cardiomyopathy; a milder childhood form with later onset, characterized by hypoketotic hypoglycemia, low mortality and rare cardiomyopathy; an adult form, with isolated skeletal muscle involvement, rhabdomyolysis and myoglobinuria, usually triggered by exercise or fasting.
Sources
Last updated 5/8/2026, 6:38:20 AM