Isolation and characterization of 1 alpha-hydroxy-23-carboxytetranorvitamin D: a major metabolite of 1,25-dihydroxyvitamin D3.
Isolation and characterization of 1 alpha-hydroxy-23-carboxytetranorvitamin D: a major metabolite of 1,25-dihydroxyvitamin D3.
复制标题
1 α-羟基-23-羧基四去甲维生素 D 的分离和表征：1,25-二羟基维生素 D3 的主要代谢物。
作者：
R. Esvelt;H. Schnoes;H. DeLuca
用双标记放射性示踪技术研究了1 α，25-二羟维生素D3的体内侧链氧化。给予1 α，25-二羟基-[3 α-3 H]维生素D3和1 α，25-二羟基[26，27 - 14 C]维生素D3的大鼠产生具有高3 H/14 C比率的化合物。在给药后3 h内，在肠和肝脏中发现了相当数量的这些化合物。主要的侧链氧化代谢产物在DEAE-Sephadex色谱上以酸形式迁移，不含14 C。该化合物与重氮甲烷的甲酯化以良好的产率进行，并使该化合物更易于色谱纯化。从给予1 μ g 1 α，25-二羟基[3 α-3H]维生素D3的大鼠中分几步分离代谢物。代谢产物以甲酯的纯品形式获得，并被明确鉴别为1 α，3 β-二羟基-24-去甲-9，10-断-5，7，10（19）胆三烯-23-酸。建议将1，25-二羟基维生素D3的主要侧链氧化代谢产物命名为骨化酸。
The in vivo side-chain oxidation of 1 alpha,25-dihydroxyvitamin D3 was investigated by using a double-label radiotracer technique. Rats dosed with 1 alpha,25-dihydroxy-[3 alpha-3H]vitamin D3 and 1 alpha,25-dihydroxy[26,27-14C]vitamin D3 produced compounds with a high 3H/14C ratio. These compounds were found in sizable quantities in intestine and liver within 3 h after dosing. The major side-chain oxidized metabolite migrated as an acid on DEAE-Sephadex chromatography and contained no 14C. Methyl esterification of this compound with diazomethane proceeded in good yield and rendered the compound more amenable to chromatographic purification. The metabolite was isolated in several steps from rats dosed with 1 microgram of 1 alpha,25-dihydroxy[3 alpha-3H]vitamin D3. The metabolite was obtained in pure form as the methyl ester and was positively identified as 1 alpha,3 beta-dihydroxy-24-nor-9,10-seco-5,7,10(19)cholatrien-23-oic acid. The trivial name calcitroic acid is proposed for this major side-chain oxidized metabolite of 1,25-dihydroxyvitamin D3.