Vitamin D Metabolism Revised: Fall of Dogmas.
Vitamin D Metabolism Revised: Fall of Dogmas.
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DOI：
10.1002/jbmr.3884
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发表时间：
2019-11
影响因子：
6.2
通讯作者：
Bikle, Dan
中科院分区：
文献类型：
--
作者：
Bouillon, Roger;Bikle, Dan
维生素D是世界上最常用的医药产品之一。饮食摄入量不规律，因为很少有食物含有维生素D，而且通常远低于人类的需要，因此它在皮肤中的合成是维生素D的最重要来源。维生素D的全球供应通常被认为是一系列被动的事件，不受酶或激素的控制。在发现维生素D近100年后，我们了解到维生素D具有复杂的新陈代谢和类固醇激素作用。维生素D是完全不活跃的，需要复杂的代谢，首先在肝脏(主要但不是完全由CYP2R1)转化为25-羟基维生素D(25OHD)，然后由CYP27B1第二次羟化生成1，25-二羟基维生素D(1，25(OH)2D)。通常认为，细胞色素P450 2受体1是结构性表达的。因此，25OHD的产生被认为主要是底物依赖的，因此血清25OHD反映了维生素D的全球供应。肾脏中的CYP27B1是循环中1，25D的唯一来源，并受到不同离子和激素的严格调控，因此它的行为像一个经典的反馈调节激素系统。细胞色素P27B1在许多肾脏外组织中也广泛表达，因此1，25(OH)2D也表现为旁分泌/自分泌方式。在这些组织中，它的活动受到不同于肾脏的各种机制的调节。虽然维生素D的已知代谢物大约有50种，但临床上使用血清25OHD的测量来确定维生素D的状态，而血清1，25(OH)2D用于评估维生素D内分泌系统的生物活性。血清中维生素D的所有代谢物都与一种特定的结合蛋白--维生素D结合蛋白(DBP)有相对较高的亲和力。这种蛋白质具有高度的多态，在血清中以高浓度循环，因此所有维生素D代谢物的游离浓度都很低。1，25(OH)2D与维生素D受体(VDR)结合，存在于大多数细胞中。这种激素系统作为大多数类固醇和甲状腺激素发挥作用，调节大量参与钙和磷运输的基因，但也调节非常大量的基因(高达斑马鱼等一些生物所有基因的10%)，而不参与离子运输或骨骼代谢(Bouillon及其同事回顾(1))。
Vitamin D is one of the most frequently used medicinal prod-ucts around the world. The dietary intake is irregular because few food items contain vitamin D and is usually well below human requirements, so that its synthesis in the skin is the most important source of vitamin D. The global supply of vitamin D is usually considered as a passive series of events, not controlled by enzymes or hormones. In the nearly 100 years after its discovery, we learned that vitamin D has a complex metabolism and steroidlike hormonal action. Vitamin D is totally inactive and requires a complex metabolism, first in the liver (mostly but not exclusively by CYP2R1) into 25-hydroxyvitamin D (25OHD), followed by a second hydroxylation by CYP27B1 into 1, 25-dihydroxyvitamin D (1, 25 (OH) 2D). CYP2R1 is usually considered to be constitutively expressed. Therefore, the production of 25OHD is considered to be mostly substrate dependent so that serum 25OHD reflects the global supply of vitamin D. CYP27B1 in the kidney is the unique source of circulating 1, 25D and is tightly regulated by different ions and hormones so that it behaves as a classical feedback regulated hormonal system. CYP27B1 is also widely expressed in many extra renal tissues so that 1, 25 (OH) 2D also behaves in a paracrine/autocrine fashion. In these tissues its activity is regulated by a variety of mechanisms different from what happens in the kidney. Although there are probably around 50 known metabolites of vitamin D, measurement of serum 25OHD is clinically used to define the vitamin D status, whereas serum 1, 25 (OH) 2D is used to assess the biological activity of the vitamin D endocrine system. All metabolites of vitamin D in serum are bound with relatively high affinity to a specific binding protein, vitamin D binding protein (DBP). This protein is highly polymorphic and circulates in serum in high concentrations so that the free concentrations of all vitamin D metabolites are very low. 1, 25 (OH) 2D binds to the vitamin D receptor (VDR), present in most cells. This hormonal system functions as most steroid and thyroid hormones and regulates a very large number of genes involved in calcium and phosphate transport but also regulates a very large number of genes (up to 10% of all genes of the some organisms such as the zebrafish) not involved in ion transport or bone metabolism (reviewed in Bouillon and colleagues (1)).
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影响因子：
20.3
作者：
Bouillon R;Marcocci C;Carmeliet G;Bikle D;White JH;Dawson-Hughes B;Lips P;Munns CF;Lazaretti-Castro M;Giustina A;Bilezikian J
通讯作者：
Bilezikian J
影响因子：
3.5
作者：
Ahn J;Yu K;Stolzenberg-Solomon R;Simon KC;McCullough ML;Gallicchio L;Jacobs EJ;Ascherio A;Helzlsouer K;Jacobs KB;Li Q;Weinstein SJ;Purdue M;Virtamo J;Horst R;Wheeler W;Chanock S;Hunter DJ;Hayes RB;Kraft P;Albanes D
通讯作者：
Albanes D
影响因子：
158.5
作者：
BARBOUR, GL;COBURN, JW;HORST, RL
通讯作者：
HORST, RL
影响因子：
4.1
作者：
Cools, M.;Goemaere, S.;Bouillon, R.
通讯作者：
Bouillon, R.
DOI：
10.1038/bonekey.2013.214
发表时间：
2014-01-08
期刊：
BoneKEy reports
影响因子：
--
作者：
Bouillon, Roger;Suda, Tatsuo
通讯作者：
Suda, Tatsuo