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Journal of Lipid Research, Vol. 48, 185-192, January 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Patient-Oriented Research

Cholestanol metabolism in patients with cerebrotendinous xanthomatosis: absorption, turnover, and tissue deposition

Ashim K. Bhattacharyya^*, Don S. Lin and William E. Connor^1,

^* Departments of Pathology and Physiology, Louisiana State University Health Sciences Center, New Orleans, LA
Department of Medicine, Oregon Health and Science University, Portland, OR

Published, JLR Papers in Press, October 1, 2006.

¹ To whom correspondence should be addressed. e-mail: connorw{at}ohsu.edu

ABSTRACT

To study the metabolism of cholestanol in patients with cerebrotendinous xanthomatosis (CTX), we measured the cholestanol absorption, the cholesterol and cholestanol turnover, and the tissue content of sterols in two patients. Cholestanol absorption was 5.0%. The rapid exchangeable pool of cholestanol was 233 mg, and the total exchangeable pool was 752 mg. The production rate of cholestanol in pool A was 39 mg/day. [4-¹⁴C]cholestanol was detected in the xanthomas, but neither [4-¹⁴C]cholestanol nor [4-¹⁴C]cholesterol was detected in peripheral nerves biopsied at 49 and 97 days after [4-¹⁴C]cholesterol given intravenously. Of the 18 tissues analyzed at biopsy and autopsy, the cholestanol content varied from 0.09 mg/g in psoas muscle to 76 mg/g in a cerebellar xanthoma. With the assumption that the cholestanol-to-cholesterol ratio is 1.0, the relative cholestanol-to-cholesterol ratio varied from 1.0 in plasma and liver to 30.0 in the cerebellar xanthoma; cholestanol was especially high in nerve tissue. Our data indicate that CTX patients absorb cholestanol from the diet. They have a higher than normal cholestanol production rate. Cholestanol was derived from cholesterol. In CTX patients, the blood-brain barrier was intact to the passage of [4-¹⁴C]cholesterol and [4-¹⁴C]cholestanol. The deposition of large amounts of cholestanol (up to 30% of total sterols in cerebellum) in nerve tissues must have an important role in the neurological symptoms in CTX patients. In view of the intact blood-brain barrier, several other explanations for the large amounts of cholestanol in the brain were postulated.

Supplementary key words neurological disorders • cholesterol and cholestanol turnover • blood brain barrier • brain sterols • brain cholestanol • chenodeoxycholic acid • sterol 27-hydroxylase • 27-hydoxy cholesterol • 7-hydroxy-4 cholesten-3-one

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				U. Panzenboeck, U. Andersson, M. Hansson, W. Sattler, S. Meaney, and I. Bjorkhem On the mechanism of cerebral accumulation of cholestanol in patients with cerebrotendinous xanthomatosis J. Lipid Res., May 1, 2007; 48(5): 1167 - 1174. [Abstract] [Full Text] [PDF]