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.