Batta A K, Salen G, Shefer S, Tint G S, Batta M
Department of Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103.
J Lipid Res. 1987 Aug;28(8):1006-12.
Large quantities of C27 bile alcohols hydroxylated at C-25 are excreted in the bile and urine of patients with cerebrotendinous xanthomatosis, a lipid storage disease that results from defective bile acid synthesis. The presence of both biliary and urinary bile alcohols reflects impaired bile acid synthesis. After treatment of samples with beta-glucuronidase, plasma bile alcohols were quantitated by gas-liquid chromatography-mass spectrometry. 5 beta-Cholestane-3 alpha,7 alpha,12 alpha,25-tetrol (334 micrograms/dl) was found to be the major bile alcohol, followed by 5 beta-cholestane-3 alpha,7 alpha,12 alpha,23R,25-pentol (65 micrograms/dl), and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24(R and S),25-pentols (62.5 micrograms/dl and 64.5 micrograms/dl, respectively) in the plasma of these patients. When compared to biliary and urinary bile alcohol excretions, the plasma pattern resembled bile where 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol glucuronide predominated. In contrast, urinary bile alcohols were composed chiefly of 5 beta-cholestanepentol glucuronides with only small amounts of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol glucuronide. Treatment with chenodeoxycholic acid, which suppresses abnormal bile acid synthesis in these patients, reduced plasma bile alcohol concentrations dramatically. These results show that large quantities of bile alcohol glucuronides, particularly 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrolglucuronide, circulate in plasma of patients with cerebrotendinous xanthomatosis. The plasma bile alcohols closely resemble biliary bile alcohols which indicates their hepatic origin. The large quantities of polyhydroxylated bile alcohols in the urine may suggest their formation, at least in part, from 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol by renal hydroxylating mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
大量在C - 25位羟基化的C27胆汁醇在脑腱性黄瘤病患者的胆汁和尿液中排泄，脑腱性黄瘤病是一种由胆汁酸合成缺陷导致的脂质贮积病。胆汁和尿液中胆汁醇的存在反映了胆汁酸合成受损。用β - 葡萄糖醛酸酶处理样品后，通过气液色谱 - 质谱法对血浆胆汁醇进行定量。发现5β - 胆甾烷 - 3α，7α，12α，25 - 四醇（334微克/分升）是主要的胆汁醇，其次是5β - 胆甾烷 - 3α，7α，12α，23R，25 - 五醇（65微克/分升），以及5β - 胆甾烷 - 3α，7α，12α，24（R和S），25 - 五醇（分别为62.5微克/分升和64.5微克/分升）在这些患者的血浆中。与胆汁和尿液中胆汁醇的排泄情况相比，血浆模式类似于以5β - 胆甾烷 - 3α，7α，12α，25 - 四醇葡萄糖醛酸为主的胆汁。相反，尿液中的胆汁醇主要由5β - 胆甾烷五醇葡萄糖醛酸组成，只有少量的5β - 胆甾烷 - 3α，7α，12α，25 - 四醇葡萄糖醛酸。用鹅去氧胆酸治疗可抑制这些患者异常的胆汁酸合成，显著降低血浆胆汁醇浓度。这些结果表明，大量的胆汁醇葡萄糖醛酸，尤其是5β - 胆甾烷 - 3α，7α，12α，25 - 四醇葡萄糖醛酸，在脑腱性黄瘤病患者的血浆中循环。血浆胆汁醇与胆汁中的胆汁醇非常相似，这表明它们起源于肝脏。尿液中大量的多羟基化胆汁醇可能表明它们至少部分是通过肾脏羟化机制由5β - 胆甾烷 - 3α，7α，12α，25 - 四醇形成的。（摘要截取自250字）
