Department of Biological Informatics and Experimental Therapeutics, Akita University Graduate School of Medicine, Akita 010-8543, Japan.
Circ J. 2013;77(2):301-8. doi: 10.1253/circj.cj-12-1544. Epub 2013 Jan 18.
Angiotensin-converting enzyme 2 (ACE2) is a negative regulator of the renin-angiotensin system, and functions as the key SARS coronavirus receptor and stabilizer of neutral amino acid transporters. ACE2 catalyzes the conversion of angiotensin II to angiotensin 1-7, thereby counterbalancing ACE activity. Accumulating evidence indicates that the enzymatic activity of ACE2 has a protective role in cardiovascular diseases. Loss of ACE2 can be detrimental, as it leads to functional deterioration of the heart and progression of cardiac, renal, and vascular pathologies. Recombinant soluble human ACE2 protein has been demonstrated to exhibit beneficial effects in various animal models, including cardiovascular diseases. ACE2 is a multifunctional enzyme and thus potentially acts on other vasoactive peptides, such as Apelin, a vital regulator of blood pressure and myocardium contractility. In addition, ACE2 is structurally a chimeric protein that has emerged from the duplication of 2 genes: homology with ACE at the carboxypeptidase domain and homology with Collectrin in the transmembrane C-terminal domain. ACE2 has been implicated in the pathology of Hartnup's disease, a disorder of amino acid homeostasis, and, via its function in amino acid transport, it has been recently revealed that ACE2 controls intestinal inflammation and diarrhea, thus regulating the gut microbiome. This review summarizes and discusses the structure and multiple functions of ACE2 and the relevance of this key enzyme in disease pathogenesis.
血管紧张素转换酶 2（ACE2）是肾素-血管紧张素系统的负调节剂，作为关键的 SARS 冠状病毒受体和中性氨基酸转运体稳定剂发挥作用。ACE2 催化血管紧张素 II 转化为血管紧张素 1-7，从而抵消 ACE 的活性。越来越多的证据表明，ACE2 的酶活性在心血管疾病中具有保护作用。ACE2 的缺失可能是有害的，因为它会导致心脏功能恶化，并促进心脏、肾脏和血管病变的进展。重组可溶性人 ACE2 蛋白已被证明在包括心血管疾病在内的各种动物模型中具有有益作用。ACE2 是一种多功能酶，因此可能作用于其他血管活性肽，如 Apelin，它是血压和心肌收缩力的重要调节剂。此外，ACE2 是一种嵌合蛋白，它是由 2 个基因的复制而产生的：羧肽酶结构域与 ACE 的同源性和跨膜 C 端结构域与 Collectrin 的同源性。ACE2 与 Hartnup 病的病理学有关，Hartnup 病是一种氨基酸稳态紊乱，通过其在氨基酸转运中的功能，最近发现 ACE2 控制肠道炎症和腹泻，从而调节肠道微生物组。这篇综述总结和讨论了 ACE2 的结构和多种功能，以及这种关键酶在疾病发病机制中的相关性。
