Journal of Lipid Research, Vol. 20, 22-30, January 1979
Copyright © 1979 by Lipid Research, Inc.

Metabolism of potential precursors of chenodeoxycholic acid in cerebrotendinous xanthomatosis (CTX)

G. Salen , S. Shefer , E. H. Mosbach , S. Hauser , B. I. Cohen , and G. Nicolau

The Veterans Administration Hospital, East Orange, NJ 07019; the Department of Medicine, College of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103; the Public Health Research Institute of The City of New York, Inc., New York 10016; and the Cabrini Medical Center, New York, NY 10003

In patients with cerebrotendinous xanthomatosis (CTX), diminished cholic acid production is associated with incomplete oxidation of the cholesterol side chain and the excretion of C₂₅-hydroxy bile alcohols. The aims of this investigation were 1) to provide quantitative information on the pool size and production rate of chenodeoxycholic acid by the isotope dilution technique; and 2) to investigate the possible existence of a block in chenodeoxycholic acid synthesis and explain the absence of chenodeoxycholic acid precursors in CTX.

After the injection of [24-¹⁴C]chenodeoxycholic acid, measurements of chenodeoxycholic acid pool size and production rate in a CTX subject were, respectively, 1/20 and 1/6 as great as controls. Further, three potential precursors of chenodeoxycholic acid, namely [G-³H]7-hydroxy-4-cholesten-3-one, [G-³H]5ßbeta;-cholestane-3,7,25-triol, and [G-³H]5ßbeta;-cholestane-3,7,26-triol, were administered to the CTX and control subjects and the specific activity curves of [G-³H]cholic acid and [G-³H]chenodeoxycholic acid were constructed and compared. In the control subjects, the two bile acids decayed exponentially, but in the CTX patient maximum specific activities were abnormally delayed, indicating the hindered transformation of precursor into bile acid. These results show that chenodeoxycholic acid synthesis is small in CTX and that the conversion of 7-hydroxy-4-cholesten-3-one, 5ßbeta;-cholestane-3,7,25-triol, and 5ßbeta;-cholestane-3,7,26-triol to both chenodeoxycholic acid and cholic acid were similarly impaired.

Supplementary key words cholic acid • pool size • bile acid • precursors • bile alcohols

Submitted on April 11, 1977
Revised on February 22, 1978
Accepted on May 30, 1978

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