PRIMARY STRUCTURE AND TISSUE-SPECIFIC EXPRESSION OF HUMAN BETA-HYDROXYISOBUTYRYL-COENZYME-A HYDROLASE

beta-Hydroxyisobutyryl-CoA (HIBYL-CoA) hydrolase is responsible for th e specific hydrolysis of HIBYL-CoA, a saline catabolite, as well as th e hydrolysis of beta-hydroxypropionyl-CoA, an intermediate in a minor path way of propionate metabolism, We have obtained the amino acid seq uences of several tryptic peptides derived from purified rat liver HIB YL-CoA hydrolase, and the NH2-terminal peptize sequence was matched to the translated sequence of a human expressed sequence tag present in the data base of the IMAGE Consortium (Lawrence Livermore National Lab oratory, Livermore, CA), The complete nucleotide sequence and the dedu ced amino acid sequence showed no similarity to the sequences of well known thioesterases but showed significant homology to the enoyl-CoA h ydratase/isomerase enzyme family, The cDNA fragment corresponding to t he mature (processed) protein was expressed in Escherichia coli, The p urified recombinant enzyme displayed substrate specificity very simila r to that of the rat enzyme and was specifically bound by polyclonal a ntibodies raised against purified rat liver HIBYL-CoA hydrolase, North ern and Western blot analyses with various human tissues indicated pre dominant expression in liver, heart, and kidney, with discrepancies oc curring in the amounts of HIBYL-CoA hydrolase mRNA compared to stably expressed protein in several tissues.