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Research Article Free access | 10.1172/JCI107688

A Biochemical Abnormality in Cerebrotendinous Xanthomatosis IMPAIRMENT OF BILE ACID BIOSYNTHESIS ASSOCIATED WITH INCOMPLETE DEGRADATION OF THE CHOLESTEROL SIDE CHAIN

T. Setoguchi, Gerald Salen, G. S. Tint, and E. H. Mosbach

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: 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: 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: 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: PubMed | Google Scholar

Published May 1, 1974 - More info

Published in Volume 53, Issue 5 on May 1, 1974
J Clin Invest. 1974;53(5):1393–1401. https://doi.org/10.1172/JCI107688.
© 1974 The American Society for Clinical Investigation
Published May 1, 1974 - Version history
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Abstract

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.

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