精氨酸酶催化L-精氨酸水解成L-鸟氨酸和尿素。现有的两种亚型 Arg1 和 Arg2 显示出不同的细胞定位和代谢功能。精氨酸酶活性对于尿素循环中的氮解毒、多胺的合成以及控制 L-精氨酸的生物利用度和一氧化氮的产生至关重要。尽管对精氨酸酶的生物化学和功能的理解取得了重大进展，但仍然存在一些悬而未决的问题。最近的研究表明，Arg1 和 Arg2 的调节和功能具有细胞类型特异性、物种特异性，并且在小鼠和人类中存在巨大差异。主要差异在于Arg1和Arg2在免疫细胞和红细胞中的分布和功能。与之前的想法相反，Arg1 活性似乎仅与血管壁稳态条件下的血管 NO 信号传导部分相关，但其表达在疾病条件下会增加，并且可能是精氨酸酶抑制剂治疗的目标。 Arg2 似乎主要是一种分解代谢酶，参与 L-鸟氨酸、多胺和脯氨酸的合成，但可能在血压控制中发挥推定作用，至少在小鼠中是这样。精氨酸酶介导的精氨酸消耗的免疫抑制作用是癌症治疗的一个有希望的目标。这篇综述批判性地修改和讨论了精氨酸酶的生物化学、药理学和体内功能，重点关注从细胞特异性 Arg1 和 Arg2 敲除小鼠的分析以及使用精氨酸酶抑制剂或聚乙二醇化重组精氨酸酶的人体研究中获得的见解。意义声明 该综述强调需要进一步研究，以加深我们对不同细胞类型中 Arg1 和 Arg 2 调节的理解，同时考虑到它们的定位、物种特异性以及多种生化和生理作用。这可能会导致更好的药理学策略，以针对肝脏、心血管、血液、免疫/感染疾病和癌症中的精氨酸酶活性。© 2024 作者。这是根据知识共享署名非商业许可条款的开放获取文章，允许在任何媒体中使用、分发和复制，前提是正确引用原始作品并且不将其用于商业目的。

Arginase catalyzes the hydrolysis of L-arginine into L-ornithine and urea. The two existing isoforms Arg1 and Arg2 show different cellular localizations and metabolic functions. Arginase activity is crucial for nitrogen detoxification in the urea cycle, synthesis of polyamines, and control of l-arginine bioavailability and nitric oxide production. Despite significant progress in the understanding of the biochemistry and function of arginases, several open questions remain. Recent studies have revealed that the regulation and function of Arg1 and Arg2 are cell-type-specific, species-specific, and profoundly different in mice and humans. The main differences were found in the distribution and function of Arg1 and Arg2 in immune and erythroid cells. Contrary to what was previously thought, Arg1 activity appears to be only partially related to vascular NO signaling under homeostatic conditions in the vascular wall, but its expression is increased under disease conditions and may be targeted by treatment with arginase inhibitors. Arg2 appears to be mainly a catabolic enzyme involved in the synthesis of L-ornithine, polyamine, and proline but may play a putative role in blood pressure control, at least in mice. The immunosuppressive role of arginase-mediated arginine depletion is a promising target for cancer treatment. This review critically revises and discusses the biochemistry, pharmacology, and in vivo function of arginase, focusing on the insights gained from the analysis of cell-specific Arg1 and Arg2 knockout mice and human studies using arginase inhibitors or pegylated recombinant arginase. Significance Statement The review emphasizes the need for further research to deepen our understanding of the regulation of Arg1 and Arg 2 in different cell types under consideration of their localization, species-specificity, and multiple biochemical and physiological roles. This could lead to better pharmacological strategies to target arginase activity in liver, cardiovascular, hematological, immune/infection diseases and cancer.© 2024 The Authors. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.