Kato S, Yanagisawa J, Murayama A, Kitanaka S, Takeyama K
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Curr Opin Nephrol Hypertens. 1998 Jul;7(4):377-83. doi: 10.1097/00041552-199807000-00005.
Vitamin D plays a role in a wide variety of biological events such as calcium homeostasis, bone formation and cellular differentiation. An active form of vitamin D acting as a ligand specific vitamin D receptor (VDR), 1 alpha,25(OH)2D3, is biosynthesized from cholesterol, and during this biosynthesis a renal 25-hydroxylation at the final stage by 25-hydroxyvitamin D3 1 alpha-hydroxylase is critical. Recent studies isolated the cDNA encoding 1 alpha-hydroxylase from several species, and revealed that this enzyme belongs to a member of the cytochrome p450 enzyme superfamily, with highest homologies to the p450 hydroxylases for vitamin D derivatives. One of three kinds of hereditary rickets (vitamin D-dependent rickets type I) displays an autosomal recessive trait and clinical features consistent with a defect of 1 alpha-hydroxylase activity, and the genetic analysis of the type I patients identified missense mutations of the 1 alpha(OH)ase gene that results in a loss of this enzymatic activity.
维生素D在多种生物学过程中发挥作用，如钙稳态、骨形成和细胞分化。维生素D的一种活性形式，即作为配体特异性维生素D受体（VDR）的1α,25(OH)₂D₃，是由胆固醇生物合成的，在这个生物合成过程中，肾25 - 羟化酶在最后阶段对25 - 羟基维生素D₃进行1α - 羟化是至关重要的。最近的研究从几个物种中分离出了编码1α - 羟化酶的cDNA，并揭示该酶属于细胞色素p450酶超家族的一员，与维生素D衍生物的p450羟化酶具有最高的同源性。三种遗传性佝偻病之一（I型维生素D依赖性佝偻病）表现为常染色体隐性性状，其临床特征与1α - 羟化酶活性缺陷一致，对I型患者的基因分析确定了1α(OH)ase基因的错义突变，导致该酶活性丧失。
