Acyl-coenzyme A thioesterase 8 (ACOT8)

Acyl-coenzyme A thioesterase 8 (ACOT8) is a peroxisomal enzyme that catalyzes the hydrolysis of acyl-CoA esters to free fatty acids and coenzyme A, thus regulating intracellular acyl-CoA and free fatty acid levels. It plays a significant role in fatty acid metabolism, including the β-oxidation pathway, and participates in the metabolism of bile acid CoA esters and dicarboxylic acids. ACOT8 displays broad substrate specificity for medium- to long-chain acyl-CoAs but is inactive on substrates with very long aliphatic chains. The enzyme is involved in metabolic regulation of peroxisome proliferation and interacts with the HIV-1 Nef protein, where it may mediate Nef-induced down-regulation of CD4 in T-cells, suggesting a possible link to HIV infection biology. Despite its central metabolic roles, no drugs directly target ACOT8 currently, and its function in human disease outside of rare associations remains under investigation.

Other names

ACOT8Acyl-CoA thioesterase 8ACTEIIIPTE1PTE2HACTE-IIIhACTEIIIhTENAP1Choloyl-coenzyme A thioesteraseHIV-Nef-associated acyl-CoA thioesterasePeroxisomal acyl-CoA thioesterase 2Peroxisomal acyl-coenzyme A thioester hydrolase 1Peroxisomal long-chain acyl-CoA thioesterase 1Thioesterase IIThioesterase IIICholoyl-CoA hydrolaseNef (lentivirus myristoylated factor) associated protein 1

Not applicable (no drugs established to act directly on ACOT8). Any future mechanism would likely involve inhibition or modulation of acyl-CoA hydrolysis.