ACCUMULATION OF 7-ALPHA-HYDROXY-4-CHOLESTEN-3-ONE AND CHOLESTA-4,6-DIEN-3-ONE IN PATIENTS WITH CEREBROTENDINOUS XANTHOMATOSIS - EFFECT OF TREATMENT WITH CHENODEOXYCHOLIC ACID
ACCUMULATION OF 7-ALPHA-HYDROXY-4-CHOLESTEN-3-ONE AND CHOLESTA-4,6-DIEN-3-ONE IN PATIENTS WITH CEREBROTENDINOUS XANTHOMATOSIS - EFFECT OF TREATMENT WITH CHENODEOXYCHOLIC ACID
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DOI：
10.1002/hep.1840070210
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发表时间：
1987-03-01
期刊：
影响因子：
13.5
通讯作者：
GRUNDY, S
中科院分区：
文献类型：
--
作者：
BJORKHEM, I;SKREDE, S;GRUNDY, S
最近提出的证据表明，在患有腱性黄瘤病的患者中胆固醇积累的重要部分是由于涉及7 α-胆固醇的新途径的加速。作为前体的胆汁酸生物合成中的羟基化中间体（J.Clin.Invest. 1985; 75：448-456）。由于缺乏参与胆汁酸生物合成主要途径的线粒体26-羟化酶，这些中间产物在腱性黄瘤病患者体内积累。新途径可能涉及以下步骤：7. α-羟基胆固醇→7.阿尔法。羟基-4-异戊烯-3-酮胆甾-4，6-二烯-3-酮4-异戊烯-3-酮胆固醇已经开发了用于测定7 α-基于同位素稀释-质谱法测定血清中的羟基-4-甾烯-3-酮和胆甾-4，6-二烯-3-酮。血清中7.羟基-4-异戊烯-3-酮和胆甾-4，6-二烯-3-酮以及胆甾-4，6-二烯-3-酮在三名腱性黄瘤病患者中明显升高。用鹅去氧胆酸治疗两名患者，使两种类固醇的血清水平降低了80%以上。胆甾烷醇的浓度在一名患者中降低了72%，在另一名患者中降低了48%。讨论了胆甾烷醇在腱性黄瘤病患者中的积累继发于7 α-胆甾烷醇的积累的可能性。羟基-4-甾烯-3-酮和胆甾-4，6-二烯-3-酮。
Evidence was recently presented that an essential part of the accumulation of cholesterol in patients with cerebrotendinous xanthomatosis is due to acceleration of a novel pathway, involving 7.alpha.-hydroxylated intermediates in bile acid biosynthesis as precursors (J. Clin. Invest. 1985; 75:448-456). Such intermediates accumulate in patients with cerebrotendinous xanthomatosis due to lack of the mitochondrial 26-hydroxylase involved in the major pathway for bile acid biosynthesis. The new pathway may involve the following steps: 7.alpha.-hydroxycholesterol .fwdarw. 7.alpha.-hydroxy-4-cholesten-3-one .fwdarw. cholesta-4,6-dien-3-one .fwdarw. 4-cholesten-3-one .fwdarw. cholestanol. Accurate methods have been developed for assay of 7.alpha.-hydroxy-4-cholesten-3-one and cholesta-4,6-dien-3-one in serum, based on isotope dilution-mass spectrometry. The serum levels of 7.alpha.-hydroxy-4-cholesten-3-one as well as those of cholesta-4,6-dien-3-one as well as those of cholesta-4,6-dien-3-one were found to be markedly elevated in the three patients with cerebrotendinous xanthomatosis. Treatment of two of the patients with chenodeoxycholic acid reduced the serum levels of the two steroids by more than 80%. The concentration of cholestanol was reduced by 72% in one patient and by 48% in the other. The possibility is discussed that accumulation of cholestanol in patients with cerebrotendinous xanthomatosis is secondary to accumulation of 7.alpha.-hydroxy-4-cholesten-3-one and cholesta-4,6-dien-3-one.