protein
Acetyl-CoA acetyltransferase, mitochondrial
Gene
ACAT1
Organism
Homo sapiens(9606)
Length
427 aa
Mass
45,200 Da
ACAT1 (Acetyl-CoA acetyltransferase, mitochondrial) is a mitochondrial enzyme that catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and shorter fatty acyl-CoA species (UniProt: P24752). This reversible activity represents the final step of mitochondrial beta-oxidation. The enzyme also catalyzes condensation of two acetyl-CoA molecules into acetoacetyl-CoA and thereby plays a major role in ketone body metabolism (UniProt: P24752).
ACAT1 is primarily involved in fatty acid catabolism and ketone body synthesis in mitochondria. A genetic disorder of ACAT1 function—3-ketothiolase deficiency (3KTD)—is an autosomal recessive inborn error of isoleucine catabolism characterized by intermittent ketoacidotic attacks (UniProt: P24752).
ACAT1 is associated with Alzheimer's Disease pathology. In human post-mortem AD brain tissue compared to age-matched controls, ACAT1 expression is upregulated with a mean log₂ fold-change of 0.13 across 2 subcellular fractions analyzed by TMT-labeled quantitative proteomics (Chaparral AD proteomics). This modest elevation may reflect altered mitochondrial metabolism or energy substrate utilization 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
+0.210
S3
+0.054
Mean log₂FC across detected fractions: +0.1321 (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
This is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA (PubMed:1715688, PubMed:7728148, PubMed:9744475). Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms (PubMed:1715688, PubMed:7728148, PubMed:9744475). The activity of the enzyme is reversible and it can also catalyze the condensation of two acetyl-CoA molecules into acetoacetyl-CoA (PubMed:17371050). Thereby, it plays a major role in ketone body metabolism (PubMed:1715688, PubMed:17371050, PubMed:7728148, PubMed:9744475)
Disease associations
3-ketothiolase deficiency3KTD
An autosomal recessive inborn error of isoleucine catabolism characterized by intermittent ketoacidotic attacks associated with unconsciousness. Some patients die during an attack or are mentally retarded. Urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, triglylglycine, butanone is increased. It seems likely that the severity of this disease correlates better with the environmental or acquired factors than with the ACAT1 genotype.
Sources
Last updated 5/8/2026, 6:38:14 AM