protein
Medium-chain specific acyl-CoA dehydrogenase, mitochondrial
aka MCAD
Gene
ACADM
Organism
Homo sapiens(9606)
Length
421 aa
Mass
46,588 Da
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.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
not detected
S2
+0.479
S3
not detected
Mean log₂FC across detected fractions: +0.4792 (1 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
Medium-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:1970566, PubMed:21237683, PubMed:2251268, PubMed:8823175). 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:2251268). ETF is the electron acceptor that transfers electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase) (PubMed:15159392, PubMed:25416781). Among the different mitochondrial acyl-CoA dehydrogenases, medium-chain specific acyl-CoA dehydrogenase has preference for fatty acyl-CoAs with saturated 6 to 12 carbons long primary chains, making it but can also catalyze longer chains such as C14 and C16 (PubMed:1970566, PubMed:21237683, PubMed:2251268, PubMed:8823175)
Disease associations
Acyl-CoA dehydrogenase medium-chain deficiencyACADMD
An inborn error of mitochondrial fatty acid beta-oxidation which causes fasting hypoglycemia, hepatic dysfunction and encephalopathy, often resulting in death in infancy.
Sources
Last updated 5/8/2026, 6:38:23 AM