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Research Article Free access | 10.1172/JCI107688
Public Health Research Institute of the City of New York, Inc., New York 10016
Veterans Administration Hospitals of New York, 10016
East Orange, New Jersey 07019
Department of Medicine, College of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103
Find articles by Setoguchi, T. in: JCI | PubMed | Google Scholar
Public Health Research Institute of the City of New York, Inc., New York 10016
Veterans Administration Hospitals of New York, 10016
East Orange, New Jersey 07019
Department of Medicine, College of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103
Find articles by Salen, G. in: JCI | PubMed | Google Scholar
Public Health Research Institute of the City of New York, Inc., New York 10016
Veterans Administration Hospitals of New York, 10016
East Orange, New Jersey 07019
Department of Medicine, College of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103
Find articles by Tint, G. in: JCI | PubMed | Google Scholar
Public Health Research Institute of the City of New York, Inc., New York 10016
Veterans Administration Hospitals of New York, 10016
East Orange, New Jersey 07019
Department of Medicine, College of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103
Find articles by Mosbach, E. in: JCI | PubMed | Google Scholar
Published May 1, 1974 - More info
Bile acid production in cerebrotendinous xanthomatosis (CTX) is subnormal, yet the activity of cholesterol 7α-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, 5β-cholestane-3α,7α,12α,25-tetrol and 5β-cholestane-3α,7α,12α,24ξ,25-pentol. After i.v. injection of [4-14C]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.