protein
Acetoacetyl-CoA synthetase
Gene
AACS
Organism
Homo sapiens(9606)
Length
672 aa
Mass
75,144 Da
Acetoacetyl-CoA synthetase (AACS) is a cytosolic enzyme that converts acetoacetate to acetoacetyl-CoA, catalyzing a key step in ketone body utilization and supporting the biosynthesis of cholesterol and fatty acids (UniProt: Q86V21). The protein localizes to the cytoplasm and participates in metabolic pathways essential for cellular energy metabolism and lipid homeostasis. No baseline disease associations are documented in UniProt for this protein.
AACS is relevant to Alzheimer's Disease based on proteomics evidence from post-mortem AD brain tissue. Analysis of human AD brain versus age-matched controls using tandem mass tag (TMT) labeling and data-dependent acquisition (DDA) mass spectrometry across four subcellular fractions (P2, P3, S2, S3) showed that AACS is consistently downregulated in AD (mean log2 fold-change: −0.27; Chaparral AD proteomics). This reduction in ketone body-metabolizing capacity may reflect disrupted energy metabolism in Alzheimer's pathology, potentially contributing to mitochondrial dysfunction and impaired neuronal bioenergetics observed in the disease.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.269
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.2688 (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
Converts acetoacetate to acetoacetyl-CoA in the cytosol (By similarity). Ketone body-utilizing enzyme, responsible for the synthesis of cholesterol and fatty acids (By similarity)
Sources
Last updated 5/8/2026, 6:39:45 AM