title: A biochemical abnormality in cerebrotendinous xanthomatosis. Impairment of bile acid biosynthesis associated with incomplete degradation of the cholesterol side chain.
abstract: Bile acid production in cerebrotendinous xanthomatosis (CTX) is subnormal, yet the activity of cholesterol 7alpha-hydroxylase, the rate-determining enzyme of bile acid synthesis, is elevated. To explain this discrepancy, bile acid precursors were sought in bile and feces of three CTX subjects. Over 10% of the total sterols excreted in bile and feces consisted of compounds more polar than cholesterol. Chromatographic analysis of the polar fractions in conjunction with gasliquid chromatography (GLC)-mass spectrometry indicated two major constituents, 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol and 5beta-cholestane-3alpha,7alpha,12alpha,24xi,25-pentol. After i.v. injection of [4-(14)C]cholesterol both bile alcohols were radioactive proving that they were derived from cholesterol. The accumulation of alcohols hydroxylated at C-25 and C-24,25 suggests that decreased bile acid synthesis in CTX results from impaired oxidation of the cholesterol side chain. This finding and the virtual absence of intermediates hydroxylated at C-26 indicate that current views of the major pathway of bile acid synthesis may require revision.
mesh_terms: D000438:Alcohols / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002250:Carbon Radioisotopes; D002776:Cholestanes / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D002845:Chromatography; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D005243:Feces / Q000032:analysis; D006801:Humans; D013058:Mass Spectrometry; D013250:Steroid Hydroxylases / Q000378:metabolism; D014973:Xanthomatosis / Q000201:enzymology / Q000378:metabolism*
chemical_list: D000438:Alcohols; D001647:Bile Acids and Salts; D002250:Carbon Radioisotopes; D002776:Cholestanes; D002784:Cholesterol; D013250:Steroid Hydroxylases