Thiolytic Cleavage

In peroxisomes purified from liver of control rats, two thiolase activities were found and their corresponding proteins were isolated.67 Based on N-terminal amino acid sequencing, the first one was identified as thiolase A. This is a constitutively expressed protein, that had not been isolated before but whose presence was postulated previously on the basis of mRNA analysis.68,69 It is rather similar to thiolase B, which had been purified by other groups from clofibrate treated animals. The substrate spectra of thiolase A and B are almost identical. Interestingly, thiolase A is more stable than B (Antonenkov V., Mannaerts G. P. and Van Veldhoven P. P., unpublished data). The other thiolase activity resided in SCPX, a 58 kDa protein identified initially by the presence of an SCP2 domain at its C-terminus.70 Based on the amino acid sequence deduced from its cDNA, a thiolase activity was postulated for SCPX and subsequently demonstrated with the recombinant protein.70,71 In an active form, SCPx-thiolase had not been purified before. Like thiolase A and B, SCPx-thiolase cleaves straight 3-oxoacyl-CoAs, but only SCPx-thiolase acts on the 3-oxoacyl-CoA derivatives of 2-methyl-branched fatty acids and trihydroxycoprostanic acid.67 Hence, SCPx-thiolase is indispensable for the degradation of pristanic acid and trihydroxycoprostanic acid. Based on studies with recombinant SCPX, its role in pristanic acid removal was confirmed by others.73

0 0

Post a comment