DeLuca H F
Adv Exp Med Biol. 1986;196:361-75. doi: 10.1007/978-1-4684-5101-6_24.
Vitamin D functions by stimulating intestinal calcium and phosphorus absorption, by stimulating bone calcium mobilization, and by increasing renal reabsorption of calcium in the distal tubule. These functions on bone and possibly kidney, but not intestine, require the parathyroid hormone. As a result of these functions, serum calcium and phosphorus concentrations are elevated to supersaturating levels required for the mineralization of bone to prevent rickets, osteomalacia, and hypocalcemic tetany. Recent experiments demonstrate that maintaining serum calcium and phosphorus levels in vitamin D-deficient rats in the normal range results in normal bone growth and mineralization. However, increased calcification results because bone resorption by osteoclasts is a vitamin D-dependent process. Thus, bone resorption, modeling and remodeling must be considered vitamin D-dependent processes. Vitamin D must be metabolized to 25-hydroxyvitamin D3 by the liver and subsequently by the kidney to 1,25-dihydroxyvitamin D3 before function. 1,25-Dihydroxyvitamin D3 is metabolized to a C-23 carboxylic acid (calcitroic acid) but the pathway is unknown. Although 25-hydroxyvitamin D3 is metabolized to 24R,25-dihydroxyvitamin D3, 25,26-dihydroxyvitamin D3 and 25-hydroxyvitamin D3-26,23-lactone, these pathways play no role in the function of vitamin D as shown by appropriate fluoro analogs of 25-hydroxyvitamin D3. 1,25-Dihydroxyvitamin D3 binds to a specific receptor in the intestinal nuclei to elicit a stimulation of calcium transport. 1,25-Dihydroxyvitamin D3 plus the receptor causes transcription of specific genes that code for calcium and phosphorus transport proteins. Only one protein, the calcium binding protein, has been identified as being vitamin D dependent. Two others have been described, but no clear description of the molecular mechanism of action of 1,25-dihydroxyvitamin D3 is yet available.
维生素D的作用机制包括刺激肠道对钙和磷的吸收、促进骨钙动员以及增加远端肾小管对钙的重吸收。这些对骨骼甚至可能对肾脏（而非肠道）的作用需要甲状旁腺激素的参与。由于这些作用，血清钙和磷浓度会升高至骨骼矿化所需的过饱和水平，从而预防佝偻病、骨软化症和低钙血症性手足搐搦。最近的实验表明，将维生素D缺乏大鼠的血清钙和磷水平维持在正常范围内可实现正常的骨骼生长和矿化。然而，钙化增加是因为破骨细胞的骨吸收是一个依赖维生素D的过程。因此，骨吸收、塑形和重塑都必须被视为依赖维生素D的过程。维生素D在发挥功能之前必须先在肝脏中代谢为25-羟基维生素D3，随后在肾脏中代谢为1,25-二羟基维生素D3。1,25-二羟基维生素D3会代谢为一种C-23羧酸（骨化三醇酸），但其代谢途径尚不清楚。尽管25-羟基维生素D3会代谢为24R,25-二羟基维生素D3、25,26-二羟基维生素D3和25-羟基维生素D3-26,23-内酯，但如25-羟基维生素D3的合适氟类似物所示，这些途径在维生素D的功能中不起作用。1,25-二羟基维生素D3与肠细胞核中的特定受体结合，以刺激钙的转运。1,25-二羟基维生素D3与受体结合会导致编码钙和磷转运蛋白的特定基因转录。目前仅有一种蛋白质，即钙结合蛋白，被确定为依赖维生素D。另外还有两种蛋白质也被提及，但目前尚无关于1,25-二羟基维生素D3作用分子机制的清晰描述。
