Metabolism of 1,25-dihydroxyvitamin D3: evidence for side-chain oxidation.
Metabolism of 1,25-dihydroxyvitamin D3: evidence for side-chain oxidation.
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1,25-二羟基维生素 D3 的代谢：侧链氧化的证据。
作者：
Rajiv Kumar;Deborah Harnden;H. F. Deluca
维生素 D 缺乏大鼠将 650 pmol 剂量的 25-羟基[26,27-14C]维生素 D3 和 325 pmol 剂量的 1,25-二羟基[26,27-14C]维生素 D3 的约 25% 代谢为 14CO2。肾切除术可阻止 25-羟基[26,27-14C]维生素 D3 代谢为 14CO2，但不能阻止 1,25-二羟基[26,27-14C]维生素 D3 代谢。 24,25-二羟基[26,27-14C]维生素D3中不到5%的14C被代谢为14CO2。饲喂高钙并补充维生素 D3 的饮食可显着减少由 25-羟基[26,27-14C]维生素 D3 形成的 14CO2 量，但不会减少由 1,25-二羟基[26,27-14C]维生素 D3 形成的 14CO2 量。这些结果提供了强有力的证据，表明只有 1-羟基化维生素 D 化合物，尤其是 1,25-二羟基维生素 D3 会发生侧链氧化和裂解，产生未知的代谢物和 CO2。
Approximately 7% of a 650-pmol dose of 25-hydroxyl[26,27-14C]vitamin D3 and 25% of a 325-pmol dose of 1,25-dihydroxyl[26,27-14C]vitamin D3 are metabolized to 14CO2 by vitamin D deficient rats. Nephrectomy prevents the metabolism of 25-hydroxy[26,27-14C]vitamin D3 to 14CO2 but not that of 1,25-dihydroxy[26,27-14C]vitamin D3. Less than 5% of the 14C from 24,25-dihydroxy[26,27-14C]vitamin D3 is metabolized to 14CO2. Feeding diets high in calcium and supplemented with vitamin D3 markedly diminishes the amount of 14CO2 formed from 25-hydroxy[26,27-14C]vitamin D3 but not that from 1,25-dihydroxyl[26,27-14C]vitamin D3. These results provide strong evidence that only 1-hydroxylated vitamin D compounds and especially 1,25-dihydroxyvitamin D3 undergo side-chain oxidation and cleavage to yield an unknown metabolite and CO2.