23,25-Dihydroxyvitamin D3 is liberated as a major vitamin D3 metabolite in human urine after treatment with β-glucuronidase: Quantitative comparison with 24,25-dihydroxyvitamin D3 by LC/MS/MS
23,25-Dihydroxyvitamin D3 is liberated as a major vitamin D3 metabolite in human urine after treatment with β-glucuronidase: Quantitative comparison with 24,25-dihydroxyvitamin D3 by LC/MS/MS
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用 β-葡萄糖醛酸酶处理后，23,25-二羟基维生素 D3 作为主要维生素 D3 代谢物释放到人尿液中：通过 LC/MS/MS 与 24,25-二羟基维生素 D3 进行定量比较
DOI：
10.1016/j.jsbmb.2022.106133
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Higashi Tatsuya
中科院分区：
文献类型：
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作者：
Takada Kazunari;Hagiwara Yukino;Togashi Moeka;Kittaka Atsushi;Kawagoe Fumihiro;Uesugi Motonari;Nishimoto-Kusunose Shoichi;Higashi Tatsuya
对人体中多余的25-羟基维生素D3[25（OH）D3]排泄的完整了解仍有待完成。在我们之前的研究中，24，25-二羟基维生素D3[24，25（OH）2D 3] 24-葡糖苷酸被确定为主要的尿维生素D3代谢物，而23，25-二羟基维生素D3[23，25（OH）2D 3]的葡糖苷酸是另一种感兴趣的代谢物，但尚未得到充分评价。尽管对β-葡萄糖醛酸酶（GUS）处理后尿液中释放的24，25（OH）2D 3进行了定量分析，但未提供尿液中葡萄糖醛酸化23，25（OH）2D 3量的相关信息。在本研究中，我们首先开发并验证了一种基于液相色谱/电喷雾电离-串联质谱（LC/ESI-MS/MS）的方法，用于同时定量尿液中GUS释放的23，25（OH）2D 3和24，25（OH）2D 3。尿中23，25（OH）2D 3的含量与24，25（OH）2D 3的含量基本相当，而血浆中23，25（OH）2D 3的含量远低于24，25（OH）2D 3。这些结果强烈表明，23，25（OH）2D 3比24，25（OH）2D 3更容易发生葡萄糖醛酸化，并更迅速地排泄到尿液中。此外，尿液样本中23，25（OH）2D 3与24，25（OH）2D 3的量比在白天（早晨/晚上）没有显著变化，甚至在一周的维生素D3补充（1000 IU/人/天）后也没有显著变化。我们的结论是，C-23羟基化在多余的25（OH）D3的尿排泄中起着至关重要的作用。
The complete understanding of the excretion of surplus 25-hydroxyvitamin D3[25(OH)D3] in humans remains to be accomplished. In our previous study, 24,25-dihydroxyvitamin D3[24,25(OH)2D3] 24-glucuronide was identified as a major urinary vitamin D3metabolite, while the glucuronide of 23,25-dihydroxyvitamin D3[23,25(OH)2D3] is another metabolite of interest but has not been sufficiently evaluated. Although the quantitative analysis of 24,25(OH)2D3liberated in urine by the treatment with β-glucuronidase (GUS) has been conducted, no information was provided about the amount of the glucuronidated 23,25(OH)2D3in the urine. In this study, we first developed and validated a liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS)-based method for the simultaneous quantification of 23,25(OH)2D3and 24,25(OH)2D3liberated in urine by GUS. The analysis of the urine samples revealed that the amount of 23,25(OH)2D3was almost as much as that of 24,25(OH)2D3, in contrast to the fact that the plasma concentration of 23,25(OH)2D3was much lower than that of 24,25(OH)2D3. These results strongly suggested that 23,25(OH)2D3is more susceptible to glucuronidation and more promptly excreted into urine than 24,25(OH)2D3. Furthermore, the amount ratios of 23,25(OH)2D3to 24,25(OH)2D3in the urine samples did not markedly vary during the day (morning/evening) and even by a week-long vitamin D3supplementation (1000 IU/body/day). We concluded that the C-23 hydroxylation plays a crucial role in the urinary excretion of surplus 25(OH)D3.