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Acyl-coenzyme A synthetase short-chain family member 2 (ACSS2)
- Target
- ACSS2
- Molecular classification
- Enzyme (specifically, acyl-CoA synthetase family member)
01
Overview
Acyl-coenzyme A synthetase short-chain family member 2 (ACSS2) is a cytosolic enzyme responsible for converting acetate to acetyl-CoA, a central molecule in lipid synthesis, energy metabolism, and regulation of gene expression via histone acetylation. It acts as a monomer, is regulated by sterol-responsive transcription factors, and plays essential roles in tumor adaptation, neuronal memory formation, and autophagy. ACSS2’s activity is subject to acetylation and deacetylation by sirtuins, influencing metabolic flux and epigenetic modifications. Its dysfunction or altered expression is implicated in cancer and may affect neurological and metabolic health[1][2][3][4][5].
- Other names
- Acetyl-coenzyme A synthetase 2Acetyl-CoA synthetase 2Acyl-CoA synthetase short chain family member 2ACSS2acsa_human (UniProt symbol)
02
Mechanism of action
Inhibition of acetate to acetyl-CoA conversion (by ACSS2 enzyme inhibitors); Modulation of histone acetylation (impacting gene expression and cell survival)
03
Biological functions
Lipid synthesis (via acetyl-CoA production)Energy metabolism (intermediate in TCA cycle)Regulation of histone acetylation and crotonylation (impacting gene expression and memory formation in neurons)Autophagy and lysosomal biogenesis (through interaction with transcription factors in the nucleus)
04
Disease associations
Cancer (upregulated in tumor microenvironments and linked to tumor cell survival)Neurological function (important for memory formation via histone acetylation)Other (potential links to metabolic disorders owing to its central metabolic role)
05
Safety considerations
Metabolic toxicity (potential impact on lipid and energy metabolism if inhibited)Epigenetic dysregulation (possible off-target effects on gene expression, especially in the central nervous system)Cellular stress and autophagy disruption (important for tumor survival in nutrient-deprived conditions)
06
Biomarkers
ACSS2 expression levels (biomarker for metabolic adaptation in cancer and possibly for cognitive function in neuroscience contexts)
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