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首页> 外文期刊>Cell metabolism >Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes.
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Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes.

机译：Dap1 / PGRMC1结合并调节细胞色素P450酶。

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摘要

Cytochrome P450 enzymes are heme-dependent monoxygenases that play a central role in human physiology. Despite the numerous physiological processes that P450 enzymes impact, the electron donors P450 oxidoreductase and cytochrome b5 are the only proteins known to interact with and modulate the activity of ER microsomal P450s. Here, we report that Dap1/PGRMC1 is required for ER P450 function in yeast and humans. We show that S. pombe Dap1 is a hemoprotein that binds and positively regulates Cyp51A1 and Cyp61A1, two P450s required for sterol biosynthesis. Similarly, loss of human PGRMC1 reduces activity of Cyp51A1, blocking cholesterol synthesis and increasing production of toxic sterol intermediates. PGRMC1 stably binds Cyp51A1 and human P450s from three additional families including Cyp3A4, which metabolizes pharmaceutical compounds. These findings demonstrate that PGRMC1 is required for P450 activity and suggest that interindividual variation in PGRMC1 function may impact multiple biochemical pathways and drug metabolism.
机译：细胞色素P450酶是血红素依赖性单加氧酶，在人类生理学中起着核心作用。尽管P450酶会影响许多生理过程，但电子供体P450氧化还原酶和细胞色素b5是已知与ER微粒体P450相互作用并调节其活性的唯一蛋白质。在这里，我们报道Dap1 / PGRMC1是酵母和人类中ER P450功能所必需的。我们显示粟酒裂殖酵母Dap1是一种血蛋白，可以结合并正向调节Cyp51A1和Cyp61A1，这是固醇生物合成所需的两个P450。同样，人PGRMC1的丢失会降低Cyp51A1的活性，从而阻断胆固醇的合成并增加有毒固醇中间体的产量。 PGRMC1稳定结合来自其他三个家族的Cyp51A1和人类P450，包括Cyp3A4，后者可代谢药物化合物。这些发现表明PGRMC1是P450活性所必需的，并且表明PGRMC1功能的个体差异可能会影响多个生化途径和药物代谢。

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