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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Identification of the human cytochrome P450, P450RAI-2, which is predominantly expressed in the adult cerebellum and is responsible for all-trans-retinoic acid metabolism
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Identification of the human cytochrome P450, P450RAI-2, which is predominantly expressed in the adult cerebellum and is responsible for all-trans-retinoic acid metabolism

机译：鉴定出主要在成人小脑中表达并负责全反式维甲酸代谢的人细胞色素P450，P450RAI-2

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摘要

Retinoids, particularly all-trans-retinoic acid (RA), are potent reg- ulators of cell differentiation, cell proliferation, and apoptosis. The role of all-trans-RA during development and in the maintenance of adult tissues has been well established. The control of all-trans-RA levels in cells and tissues is regulated by the balance between its biosynthesis and its catabolism to inactive metabolites. The cyto- chrome P450 enzyme P450RAl (herein renamed P450RAl-1) is par- tially responsible for this inactivation of all-trans-RA. In this report, we describe the identification, molecular cloning, and character- ization of a second related enzyme. P450RAl-2, which is also involved in the specific inactivation of all-trans-RA. Transiently transfected P450RAl-2 can convert all-trans-RA to more polar me- tabolites including 4-oxo-, 4-OH-, and 18-OH-all-trans-RA. Compe- tition experiments with other retinoids Suggest that all-trans-RA is the preferred substrate. The high level of expression of P450RAl-2, particularly in the cerebellum and pons of human adult brain. suggests a unique role for this enzyme in the protection of specific tissues from exposure to retinoids.
机译：类维生素A，特别是全反式维甲酸（RA），是细胞分化，细胞增殖和凋亡的有效调节剂。众所周知，全反式RA在发育过程中和在维持成人组织中的作用。细胞和组织中全反式RA的控制是通过其生物合成与分解成无活性代谢物之间的平衡来进行的。细胞色素P450酶P450RA1（在此更名为P450RAl-1）部分负责全反式RA的这种失活。在本报告中，我们描述了第二种相关酶的鉴定，分子克隆和表征。 P450RAl-2，其也参与全反式RA的特定灭活。瞬时转染的P450RAl-2可以将全反式RA转化为极性更大的代谢产物，包括4-氧代，4-OH和18-OH-全反式RA。与其他类维生素A的竞争实验表明，全反式RA是首选的底物。 P450RAl-2的高水平表达，特别是在成人大脑的小脑和脑桥中。提示该酶在保护特定组织免于暴露于类维生素A中的独特作用。

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