Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, United States.
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, United States.
J Inorg Biochem. 2018 Sep;186:228-234. doi: 10.1016/j.jinorgbio.2018.05.014. Epub 2018 May 23.
In this review we address the relationship between cytochromes P450 (P450) and HO. This association can affect biology in three distinct ways. First, P450s produce HO as a byproduct either during catalysis or when no substrate is present. This reaction, known as uncoupling, releases reactive oxygen species that may have implications in disease. Second, HO is used as an oxygen-donating co-substrate in peroxygenase and peroxidase reactions catalyzed by P450s. This activity has proven to be important mainly in reactions involving prokaryotic P450s, and investigators have harnessed this reaction with the aim of adaptation for industrial use. Third, HO-dependent inhibition of human P450s has been studied in our laboratory, demonstrating heme destruction and also the inactivating oxidation of the heme-thiolate ligand to a sulfenic acid (-SOH). This reversible oxidative modification of P450s may have implications in the prevention of uncoupling and may give new insights into the oxidative regulation of these enzymes. Research has elucidated many of the chemical mechanisms involved in the relationship between P450 and HO, but the application to biology is difficult to evaluate. Further studies are needed reveal both the harmful and protective natures of reactive oxygen species in an organismal context.
在这篇综述中，我们探讨了细胞色素 P450（P450）和 HO 之间的关系。这种关联可以通过三种不同的方式影响生物学。首先，P450 在催化过程中或没有底物存在时，将 HO 作为副产物产生。这种反应称为解偶联，会释放出可能对疾病有影响的活性氧物质。其次，HO 被用作 P450 催化的过氧酶和过氧化物酶反应中的氧供体辅酶。这种活性在涉及原核 P450 的反应中已被证明是重要的，研究人员已经利用这种反应，旨在为工业用途进行适应。第三，我们实验室研究了 HO 依赖性的人 P450 抑制，证明了血红素的破坏以及血红素硫醇配体的失活氧化为亚磺酸(-SOH)。P450 的这种可逆氧化修饰可能对解偶联有影响，并可能为这些酶的氧化调节提供新的见解。研究已经阐明了 P450 和 HO 之间关系中涉及的许多化学机制，但将其应用于生物学方面还很难评估。需要进一步的研究来揭示活性氧物质在机体中的有害和保护性质。
