Korsmo Hunter W, Ekperikpe Ubong S, Daehn Ilse S
Department of Medicine, Division of Nephrology, The Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1243, New York, NY 10029, USA.
Antioxidants (Basel). 2024 Jun 12;13(6):712. doi: 10.3390/antiox13060712.
Xanthine Oxidoreductase (XOR) is a ubiquitous, essential enzyme responsible for the terminal steps of purine catabolism, ultimately producing uric acid that is eliminated by the kidneys. XOR is also a physiological source of superoxide ion, hydrogen peroxide, and nitric oxide, which can function as second messengers in the activation of various physiological pathways, as well as contribute to the development and the progression of chronic conditions including kidney diseases, which are increasing in prevalence worldwide. XOR activity can promote oxidative distress, endothelial dysfunction, and inflammation through the biological effects of reactive oxygen species; nitric oxide and uric acid are the major products of XOR activity. However, the complex relationship of these reactions in disease settings has long been debated, and the environmental influences and genetics remain largely unknown. In this review, we give an overview of the biochemistry, biology, environmental, and current clinical impact of XOR in the kidney. Finally, we highlight recent genetic studies linking and risk for kidney disease, igniting enthusiasm for future biomarker development and novel therapeutic approaches targeting XOR.
黄嘌呤氧化还原酶（XOR）是一种普遍存在的必需酶，负责嘌呤分解代谢的终末步骤，最终产生尿酸，尿酸由肾脏排出体外。XOR也是超氧阴离子、过氧化氢和一氧化氮的生理来源，这些物质可作为第二信使激活各种生理途径，还会促使包括肾脏疾病在内的慢性疾病的发生和发展，而肾脏疾病在全球的患病率正在上升。XOR活性可通过活性氧的生物学效应促进氧化应激、内皮功能障碍和炎症反应；一氧化氮和尿酸是XOR活性的主要产物。然而，这些反应在疾病背景下的复杂关系长期以来一直存在争议，其环境影响和遗传学因素在很大程度上仍不清楚。在这篇综述中，我们概述了XOR在肾脏中的生物化学、生物学、环境因素以及当前的临床影响。最后，我们重点介绍了将XOR与肾脏疾病风险联系起来的近期遗传学研究，这激发了人们对未来生物标志物开发以及针对XOR的新型治疗方法的热情。
