Molecular Classification
Enzyme, Ligase
Other Names
Acetyl-coenzyme A synthetase 2-like, mitochondrial, Acetyl-CoA synthetase 2-like, AceCS2, Acetate--CoA ligase 2, KIAA1846, ACAS2L, Propionate--CoA ligase
Disease Roles
Other (may include metabolic diseases, neurological disorders—direct evidence is limited and not clearly established for major disease classes like cancer)

Acyl-CoA synthetase short-chain family member 1 Overview

Acyl-CoA synthetase short-chain family member 1 (ACSS1), also referred to as acetyl-coenzyme A synthetase 2-like, mitochondrial, is a mitochondrial enzyme that catalyzes the formation of acetyl-CoA from acetate and CoA, with ATP as a cofactor[3][4]. ACSS1 is thus critical in acetate metabolism, providing acetyl-CoA mainly for oxidation under ketogenic conditions and during thermogenesis when carbohydrate supply is limited[3][4]. While functionally related to ACSS2, ACSS1 is mitochondrial (versus cytosolic ACSS2), and provides acetyl-CoA for use in the TCA cycle rather than for lipid synthesis or histone acetylation. There are currently no drugs that target ACSS1 directly, and its disease roles remain less characterized compared to ACSS2, although its fundamental metabolic function is well recognized.

Mechanism of Action

Catalyzes the conversion of acetate (and to a lesser degree, propionate) and CoA into acetyl-CoA, using ATP[3][4]

Biological Functions

Acetate metabolism
Acetyl-CoA synthesis
Fatty acid metabolism
Energy metabolism
Thermogenesis
Tricarboxylic acid (TCA) cycle

Disease Associations

Other (may include metabolic diseases, neurological disorders—direct evidence is limited and not clearly established for major disease classes like cancer)

Safety Considerations

  • none known; no established safety concerns related to direct targeting of ACSS1 in clinical settings

Interacting Drugs

none known (no approved drugs directly target ACSS1 as a primary mechanism)

Associated Biomarkers

Biomarker
none known