ACOT8 exhibits substrate specificity mainly for short- to long-chain acyl-CoA. It is known to hydrolyze a wide range of acyl-CoA substrates, including those with saturated and unsaturated fatty acids. The enzyme’s activity is crucial for maintaining cellular lipid homeostasis and energy production.
ACOT8 is ubiquitously expressed in various tissues, with higher expression levels observed in metabolically active tissues such as the liver, kidney, and heart. Its expression is regulated by various factors, including nutritional status and hormonal signals, which modulate its activity to meet the metabolic demands of the organism.
The primary function of ACOT8 is to hydrolyze acyl-CoA thioesters, thereby releasing free fatty acids and CoA. This reaction is vital for several metabolic processes, including:
ACOT8 functions by catalyzing the hydrolysis of the thioester bond in acyl-CoA molecules. This reaction is facilitated by the enzyme’s active site, which binds to the acyl-CoA substrate and stabilizes the transition state, allowing the cleavage of the thioester bond. The enzyme’s activity is regulated by various factors, including the availability of substrates and cofactors, as well as post-translational modifications.
The expression and activity of ACOT8 are regulated by multiple mechanisms:
ACOT8 has been implicated in various metabolic disorders and diseases. For instance, alterations in its expression and activity have been associated with conditions such as obesity, diabetes, and cancer. In particular, ACOT8 has been identified as a potential biomarker for clear cell renal cell carcinoma, where its expression levels correlate with disease progression and prognosis .