cytellin and 27-norcholestane-3-7-12-24-25-pentol

The urine and feces of a patient with the rare inherited lipid storage disease, sitosterolemia and xanthomatosis, were analyzed. Substantial quantities of C26-bile alcohol, 26 (or 27)-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24S,25 xi-pentol along with 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24-tetrol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24R,25-pentol, and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol were found. The structure of the C26-bile alcohol was confirmed by direct comparison (gas-liquid chromatography-mass spectrometry and thin-layer chromatography) with a standard sample synthesized from cholic acid. The configurational assignment at C-24 was determined by lanthanide-induced circular dichroism Cotton effect measurements. The increased excretion of these C26- and C27-bile alcohols suggests an abnormality of bile acid biosynthesis in this disease.

Topics: Adolescent; Chemical Phenomena; Chemistry; Chemistry, Physical; Cholestanols; Chromatography, Gas; Chromatography, Thin Layer; Circular Dichroism; Feces; Humans; Lipid Metabolism, Inborn Errors; Oxidation-Reduction; Periodic Acid; Sitosterols; Xanthomatosis

Cholesterol was shown to be the precursor of 27-nor-5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 24,25-pentol which is the major bile alcohol in human urine. 4-[14C]-Labelled cholesterol and beta-sitosterol were administered to patients with primary biliary cirrhosis. Urine was extracted with Amberlite XAD-2 and sterol glucuronides and bile acid conjugates were isolated by ion exchange chromatography on Lipidex-DEAP. Following hydrolysis and further purification on Lipidex-DEAP, the C26 bile alcohol and methyl esters of cholic and chenodeoxycholic acids were isolated by HPLC. The specific radioactivity of the C26-pentol was the same as that of cholic acid after administration of [14C]-cholesterol. In contrast, little if any radioactivity could be detected in the C26-pentol after administration of labelled beta-sitosterol.

Topics: Bile Acids and Salts; Carbon Radioisotopes; Cholestanols; Cholesterol; Chromatography, High Pressure Liquid; Female; Humans; Liver Cirrhosis, Biliary; Methylation; Middle Aged; Sitosterols