Acyl Coenzyme A Thioesterase 4 (ACOT4)

Acyl-coenzyme A (CoA) thioesterases (ACOTs) hydrolyze acyl-CoAs to the free fatty acid and CoASH, and thereby have the potential to regulate intracellular levels of these compounds. However, the corresponding human gene cluster contains only three genes coding for full-length thioesterase proteins, of which only one is peroxisomal (ACOT4). The human ACOT4 protein catalyzes the activities of three mouse peroxisomal ACOTs (ACOT3, 4, and 5), beingactive on succinyl-CoA and medium to long chain acyl-CoAs, while ACOT1 and ACOT2 carry out similar functions to the corresponding mouse genes. These data strongly suggest that the human ACOT4 gene has acquired the functions of three mouse genes by a functional convergent evolution that also provides an explanation for the unexpectedly low number of human genes.