Mitochondrial 3-ketoacyl-CoA thiolase (ACAA2, HADHB)

Mitochondrial 3-ketoacyl-CoA thiolase is an enzyme in the mitochondrial beta-oxidation pathway that catalyzes the thiolytic cleavage of 3-oxoacyl-CoA to produce acetyl-CoA and a fatty acyl-CoA shortened by two carbons, essential for energy production from fatty acids[5][2][3]. It is encoded by the *ACAA2* and *HADHB* genes (when referring to the respective proteins) and acts as either a single enzyme (ACAA2) or as the beta subunit within the mitochondrial trifunctional protein (HADHB), which is responsible for the last three reactions of long-chain fatty acid oxidation[2][9]. Deficiency leads to rare but severe metabolic and neuromuscular disorders, often presenting with hypoglycemia, metabolic acidosis, cardiomyopathy, muscle weakness, and variable neurologic involvement, requiring dietary and metabolic management[1][9][8]. The enzyme is part of the thiolase superfamily, with multiple isozymes differing by substrate specificity and intracellular localization[3][5], and also exhibits secondary RNA-binding roles affecting mRNA stability[2][6].

Other names

Acetyl-CoA acyltransferaseBeta-ketothiolaseMitochondrial 3-oxoacyl-CoA thiolaseTrifunctional enzyme subunit beta, mitochondrialACAA2HADHB

Dietary supplementation substitutes for defective beta-oxidation, providing energy and metabolic intermediates. Ketone body administration circumvents blocked acetyl-CoA production. Resveratrol theoretically stimulates fatty acid oxidation (no proven effect in clinical use for this target).