出版社：American Society for Biochemistry and Molecular Biology
摘要：To study the metabolism of cholestanol in patients with cerebrotendinousxanthomatosis (CTX), we measured the cholestanol absorption,the cholesterol and cholestanol turnover, and the tissue contentof sterols in two patients. Cholestanol absorption was 5.0%.The rapid exchangeable pool of cholestanol was 233 mg, and thetotal exchangeable pool was 752 mg. The production rate of cholestanolin pool A was 39 mg/day. [4-14C]cholestanol was detected inthe xanthomas, but neither [4-14C]cholestanol nor [4-14C]cholesterolwas detected in peripheral nerves biopsied at 49 and 97 daysafter [4-14C]cholesterol given intravenously. Of the 18 tissuesanalyzed at biopsy and autopsy, the cholestanol content variedfrom 0.09 mg/g in psoas muscle to 76 mg/g in a cerebellar xanthoma.With the assumption that the cholestanol-to-cholesterol ratiois 1.0, the relative cholestanol-to-cholesterol ratio variedfrom 1.0 in plasma and liver to 30.0 in the cerebellar xanthoma;cholestanol was especially high in nerve tissue. Our data indicatethat CTX patients absorb cholestanol from the diet. They havea higher than normal cholestanol production rate. Cholestanolwas derived from cholesterol. In CTX patients, the blood-brainbarrier 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 tissuesmust have an important role in the neurological symptoms inCTX patients. In view of the intact blood-brain barrier, severalother explanations for the large amounts of cholestanol in thebrain 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
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
