23,25-Dihydroxy-24-oxovitamin D3: a metabolite of vitamin D3 made in the kidney.
23,25-Dihydroxy-24-oxovitamin D3: a metabolite of vitamin D3 made in the kidney.
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23,25-二羟基-24-氧代维生素 D3：肾脏中产生的维生素 D3 的代谢产物。
DOI：
10.1021/bi00277a009
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发表时间：
1983
期刊：
影响因子：
2.9
通讯作者：
Norman,AW
中科院分区：
文献类型：
--
作者：
Mayer,E;Reddy,GS;Chandraratna,RA;Okamura,WH;Kruse,JR;Popjàk,G;Bishop,JE;Norman,AW
Eberhard Mayer，G. Satyanarayana Reddy，* Roshantha A. S.威廉？拉拉特纳杰伊·冈村放大图片创作者：乔治波普亚克.毕肖普和安东尼·W.诺曼 * 摘要：大鼠的肾匀浆产生了一种新的代谢产物25-羟基维生素D3，它已被分离出来的纯形式后，五个柱层析步骤。经紫外、红外吸收分光光度法、质谱、核磁共振氢谱鉴定为23，25-二羟基-24-氧代维生素D_3。C-23位的立体化学尚不清楚。25-羟基-24-氧代维生素D3，也已从该系统中分离出纯品，被发现是体外新代谢物的前体。用两种不同的方法诱导新代谢产物的产生：（a）用灌流液中含有的1，25-二羟维生素D_3灌注肾脏和（B）在完整动物体内注射1，25-二羟维生素D_3。在维生素D缺乏鸡的肠道钙转运和骨钙动员试验中，剂量水平为5.3 nmol的23，25-二羟基-24-氧代维生素D3没有生物活性。提出了一种代谢途径来描述结果;它导致25-羟基维生素D3-* 24（J？），25-· 25-羟基-24-氧代维生素D3-23，25-二羟基-24-氧代-维生素D3。已知开环甾类维生素D3在发挥其生物效应之前经历代谢转化（Norman，1979）。维生素的主要循环形式25-OH-D3“经肾脏进一步加工产生1，25（OH）2D 3或24（7？），25（OH）2D3。1，25（OH）2D 3对肠的类固醇激素样作用（Tsai等人，1972;波义耳等人，1972）、骨架（Wong等人，1972 a，B）和多种其它靶组织（Walters等，#19981;已建立。相比之下，24（7？），25（OH）2D 3与可归因于维生素D3的生物反应谱的关系仍然是一个有争议的问题（Norman等人，1982 a，B）。基于25-OH-D3的24，24-二氟化类似物的实验，一些工作者得出结论，24-羟基化在维生素D的已知作用中不起作用（米勒等人，1981; Ameenuddin等人，1982年）。另一方面，据报道，24（R），25（OH）2D 3是小鸡正常骨形成所需的（Ornoy等人，1978; Malluche等人，
Eberhard Mayer, G. Satyanarayana Reddy,* Roshantha A. S. Chandraratna, William H. Okamura, Jay R. Kruse, George Popjak, June E. Bishop, and Anthony W. Norman* abstract: Kidney homogenates of rats produced a new metabolite of 25-hydroxyvitamin D3 which has been isolated in pure form after five column chromatographic steps. It was identified as 23, 25-dihydroxy-24-oxovitamin D3 by means of ultraviolet and infrared absorption spectrophotometry, mass spectrometry, and proton nuclear magnetic resonance spec-trometry. The stereochemistry at the C-23 position is as yet unknown. 25-Hydroxy-24-oxovitamin D3, which also has been isolated in pure form from this system, was found to be the precursor of the new metabolite in vitro. The production of the new metabolite was induced by two different methods:(a) perfusion of the kidneys with 1, 25-dihydroxyvitamin D3 con-tained in the perfusate and (b) injection of 1, 25-dihydroxy-vitamin D3 in the intact animal. 23, 25-Dihydroxy-24-oxovitamin D3 was not biologically active in an assay for intestinal calcium transport and bone calcium mobilization in the vitamin D deficient chick at a dose level of 5.3 nmol. A metabolic pathway is proposed to describe the results; it leads from 25-hydroxyvitamin D3-* 24 (J?), 25-dihydroxyvitamin D3-*• 25-hydroxy-24-oxovitamin D3—23, 25-dihydroxy-24-oxo-vitamin D3. e secosteroid vitamin D3 is known to undergo metabolic conversion before exerting its biological effects (Norman, 1979). The major circulating form of the vitamin, 25-OH-D3,'is further processed by the kidney to yield l, 25 (OH) 2D3 or 24 (7?), 25 (OH) 2D3. The steroid hormone-like actions of l, 25 (OH) 2D3 on the intestine (Tsai et al., 1972; Boyle et al., 1972), skeleton (Wong et al., 1972a, b), and a variety of other target tissues (Walters et al., 1981) are well established. In contrast, the contribution of 24 (7?), 25 (OH) 2D3 to the spectrum of biological responses attributable to vitamin D3 is still a controversial issue (Norman et al., 1982a, b). On the basis of experiments with a 24, 24-difluorinated analogue of 25-OH-D3, some workers have concluded that 24-hydroxylation does not play a role in the known actions of vitamin D (Miller et al., 1981; Ameenuddin et al., 1982). On the other hand, it was reported that 24 (R), 25 (OH) 2D3 is required for normal bone formation in the chick (Ornoy et al., 1978; Malluche et al.,