Biliary metabolites of all-trans-retinoic acid in the rat: isolation and identification of a novel polar metabolite.
Biliary metabolites of all-trans-retinoic acid in the rat: isolation and identification of a novel polar metabolite.
复制标题
大鼠全反式视黄酸的胆汁代谢物：新型极性代谢物的分离和鉴定。
DOI：
10.1021/bi00257a010
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发表时间：
1982
期刊：
影响因子：
2.9
通讯作者：
DeLuca,HF
中科院分区：
文献类型：
--
作者：
Skare,KL;Schnoes,HK;DeLuca,HF
Kevin L. Skare,** Heinrich K. Schnoes, and Hector F. DeLuca*摘要：研究了生理和药理剂量的全反式-[11,12 - 3h2]维甲酸对正常大鼠胆道代谢产物的影响。在最初24小时内排泄的胆道代谢物约占放射性标记剂量的60-65%。采用Sephadex LH-20色谱法和高效液相色谱法纯化了一种主要的极性代谢物。离子交换柱的高效液相色谱显示，该代谢物带负电荷，占总胆道放射性的10%（剂量的6%）。通过傅里叶变换质子核磁共振谱、高、低分辨率质谱、快速原子轰炸质谱、紫外吸收分光光度法、傅里叶变换红外光谱、氨基酸分析和化学衍生鉴定，该极性化合物为2-[8-[6-（羟甲基）- 2,6 -二甲基-3-氧-1-环己烯-1-基]- 2,6 -二甲基- 5,7 -八-二氨基]乙磺酸。由all-fra/zs-维甲酸生成该代谢物所需的代谢转化如下：(1)环己烯环4号碳上的烯丙基氧化生成4-酮基，(2)1号碳上的一个甲基羟基化
Kevin L. Skare,** Heinrich K. Schnoes, and Hector F. DeLuca* abstract: The biliary metabolites from normal ratsdosed with either pharmacological or physiological doses of all-trans-[11, 12-3H2] retinoic acid were investigated. Biliary metabolites excreted during the first 24 h account for ap-proximately 60-65% of the radiolabeled dose. A major polar metabolite was purified to homogeneity by using Sephadex LH-20 chromatography andseveral high-performance liquid chromatographic procedures. This metabolite was negatively charged as revealed by high-performance liquid chromatography on ion-exchange columns and accounts for 10% of the total biliary radioactivity (6% of the dose). The polar com-pound was positively identified by using Fourier transform proton nuclear magnetic resonance spectroscopy, high-and low-resolution mass spectrometry, fast atom bombardment mass spectrometry, ultraviolet absorption spectrophotometry, Fourier transform infrared spectroscopy, amino acid analysis, and chemicalderivatization as 2-[8-[6-(hydroxymethyl)-2, 6-dimethyl-3-oxo-1-cyclohexen-1-yl]-2, 6-dimethyl-5, 7-octa-dienamido] ethanesulfonic acid. The metabolic transformations required for the generation of this metabolite fromall-fra/zs-retinoic acid are the following:(1) allylic oxidation at carbon 4 of the cyclohexene ring to produce a 4-keto group,(2) hydroxylation of one of the methyl groups at carbon 1