STEROL CARRIER PROTEIN-X (SCPX) IS A PEROXISOMAL BRANCHED-CHAIN BETA-KETOTHIOLASE SPECIFICALLY REACTING WITH 3-OXO-PRISTANOYL-COA - A NEW, UNIQUE ROLE FOR SCPX IN BRANCHED-CHAIN FATTY-ACID METABOLISM IN PEROXISOMES

One of the most important functions of peroxisomes, at least in humans , is the beta-oxidation of a range of different fatty acids and fatty acid derivatives. Recent studies have shown that the enzymatic machine ry required for the beta-oxidations of these substrates, may be much m ore complex as originally thought. We now report that the conventional peroxisomal thiolase which has sofar been thought to catalyze the thi olytic cleavage of the 3-oxoacyl-CoA esters of all fatty acids oxidize d in peroxisomes, shows poor reactivity towards the 3-oxoacyl-CoA este rs of 2-methyl branched-chain fatty acids such as pristanic acid. Our data further show, that SCPx, a 58 kDa protein with both thiolase and sterol carrier protein activity but unknown function sofar, readily re acts with 3-oxopristanoyl-CoA. Taken together, our data show that SCPx plays a central role in branched chain fatty acid beta-oxidation in p eroxisomes. This finding has major implications not only for the funct ional organization of the peroxisomal beta-oxidation system but also f or studies dealing with the resolution of the underlying defect in pat ients with some defect in peroxisomal beta-oxidation. (C) 1997 Academi c Press.