Rat liver peroxisomes catalyze the initial step in cholesterol synthesis. The condensation of acetyl-CoA units into acetoacetyl-CoA.
In the last few years, it has been demonstrated by this group and others that rat liver peroxisomes participate in cholesterol synthesis. It has been shown that the key regulatory enzyme of isoprenoid biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase, is present in liver cells not only in the endoplasmic reticulum but also within peroxisomes. It has been also demonstrated that rat liver peroxisomes in the presence of cytosolic proteins in vitro are able to convert [14C]mevalonic acid to [14C]cholesterol. In addition, a recent study demonstrated that the largest cellular concentration of sterol carrier protein-2 is inside peroxisomes. It is of interest, therefore, to inquire whether other proteins known to be involved in cholesterol biogenesis are also present in peroxisomes. In this study we investigated the first step in cholesterol synthesis, the condensation of two acetyl-CoA units to acetoacetyl-CoA. It was demonstrated that peroxisomal thiolase, purified by DEAE-phosphocellulose chromatography from gemfibrozil-treated rats, is active not only toward acetoacetyl-CoA and 3-ketoacyl-CoA, consistent with literature reports, but is also capable of converting acetyl-CoA units to acetoacetyl-CoA. This is the first demonstration of condensation activity in rat liver peroxisomes.
Thompson
S L
SL
Department of Biology, San Diego State University, California 92182.
Krisans
S K
SK
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000101:Acetyl-CoA C-Acetyltransferase / Q000302:isolation & purification / Q000378:metabolism*; D000123:Acetyltransferases / Q000378:metabolism*; D000214:Acyl Coenzyme A; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D002784:Cholesterol / Q000096:biosynthesis*; D003600:Cytosol / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D015248:Gemfibrozil / Q000494:pharmacology; D015151:Immunoblotting; D008099:Liver / Q000187:drug effects / Q000648:ultrastructure*; D008297:Male; D008830:Microbodies / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D000214:Acyl Coenzyme A; C010667:acetoacetyl CoA; D000105:Acetyl Coenzyme A; D002784:Cholesterol; D002374:Catalase; D000123:Acetyltransferases; D000101:Acetyl-CoA C-Acetyltransferase; D015248:Gemfibrozil