Bile acid synthesis during development. Mitochondrial 12 alpha-hydroxylation in human fetal liver.
Hydroxylation of 5 beta-[7 beta-3H]cholestane-3 alpha, 7 alpha-diol was studied in mitochondrial preparations from human fetal livers. The livers were obtained at legal abortions between weeks 14 and 24. In addition to hydroxylation in the 26-position, 5 beta-cholestane-3 alpha, 7 alpha-diol was hydroxylated in the 12 alpha-position. In one experiment, mitochondrial protein was solubilized and partially purified. Material with such chromatographic properties as those of cytochrome P450 showed 12 alpha-hydroxylase activity when combined with adrenodoxin and adrenodoxin reductase from bovine adrenal mitochondria. Because adrenodoxin and adrenodoxin reductase are components specific for mitochondrial hydroxylase systems, the results exclude microsomal contamination as the origin of this 12 alpha-hydroxylase activity. Further, there was no hydroxylase activity when NADPH-cytochrome P450 reductase from rat liver microsomes was added instead of adrenodoxin and adrenodoxin reductase. The microsomal fraction of fetal liver was also shown to possess 12 alpha-hydroxylase activity. Microsomal and mitochondrial hydroxylase activities per milligram of protein towards 5 beta-cholestane-3 alpha, 7 alpha-diol were of the same order of magnitude. The occurrence of an efficient sterol nucleus hydroxylase activity in liver mitochondria appears to be unique for fetal liver.
D000325:Adrenodoxin / Q000378:metabolism; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002777:Cholestanols / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005287:Ferredoxin-NADP Reductase / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D066298:In Vitro Techniques; D008930:Mitochondria, Liver / Q000378:metabolism*; D013253:Steroid 12-alpha-Hydroxylase / Q000378:metabolism
D001647:Bile Acids and Salts; D002777:Cholestanols; D000325:Adrenodoxin; C007426:dihydroxycoprostane; D003577:Cytochrome P-450 Enzyme System; D013253:Steroid 12-alpha-Hydroxylase; D005287:Ferredoxin-NADP Reductase