FAMILIAL GIANT-CELL HEPATITIS ASSOCIATED WITH SYNTHESIS OF 3-BETA, 7-ALPHA-DIHYDROXY-5-CHOLENOIC AND 3-BETA, 7-ALPHA, 12-ALPHA-TRIHYDROXY-5-CHOLENOIC ACIDS
FAMILIAL GIANT-CELL HEPATITIS ASSOCIATED WITH SYNTHESIS OF 3-BETA, 7-ALPHA-DIHYDROXY-5-CHOLENOIC AND 3-BETA, 7-ALPHA, 12-ALPHA-TRIHYDROXY-5-CHOLENOIC ACIDS
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DOI：
10.1172/jci112915
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发表时间：
1987-04-01
影响因子：
15.9
通讯作者：
SJOVALL, J
中科院分区：
文献类型：
--
作者：
CLAYTON, PT;LEONARD, JV;SJOVALL, J
本文采用离子交换色谱和气相色谱-质谱联用（GC-MS）分析了3岁男孩胆汁淤积性黄疸的尿胆汁酸。快速原子轰击质谱法（FAB-MS）的分析结果支持了含有烯丙基羟基的不稳定硫酸胆烯酸的存在。通过薄层色谱和高效液相色谱对FAB-MS检测到的化合物进行分离。硫酸酸化的胆汁酸可在酸化的四氢呋喃中溶解，甘氨酸缀合物可在胆酰甘氨酸水解酶中部分水解。在用重氮甲烷溶液溶解、解偶和甲基化后，用气相色谱-质谱法鉴定了三甲基硅基衍生物的胆汁酸。尿液中主要的胆汁酸是3 -，7 -。-硫酸二羟基-5-胆烯酸，3-,7 -,12 --三羟基-5-胆烯酸单硫酸酯及其甘氨酸缀合物。尿和血浆中未检出鹅去氧胆酸和胆酸。家族谱系提示胆囊酸合成异常是一种常染色体隐性遗传病，可导致儿童早期肝硬化。
Urinary bile acids from a 3-mo-old boy with cholestatic jaundice were analyzed by ion exchange chromatography and gas chromatography-mass spectrometry (GC-MS). This suggested the presence of labile sulfated cholenoic acids with an allylic hydroxyl group, a conclusion supported by analysis using fast atom bombardment mass spectrometry (FAB-MS). The compounds detected by FAB-MS were separated by thin layer chromatography and high performance liquid chromatography. The sulfated bile acids could be solvolyzed in acidified tetrahydrofuran, and glycine conjugates were partially hydrolyzed by cholylglycine hydrolase. Following solvolysis, deconjugation, and methylation with diazomethane, the bile acids were identified by GC-MS of trimethylsilyl derivatives. The major bile acids in the urine were 3.beta.,7.alpha.-dihydroxy-5-cholenoic acid 3-sulfate, 3.beta.,7.alpha.,12.alpha.-trihydroxy-5-cholenoic acid monosulfate, and their glycine conjugates. Chenodeoxycholic acid and cholic acid were undetectable in urine and plasma. The family pedigree suggested that abnormal bile acid synthesis was an autosomal recessive condition leading to cirrhosis in early childhood.