Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1175175 (SARS)
 19,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Discovery of ACE2 (angiotensin-converting enzyme 2) revealed that the renin-angiotensin system has 2 counterbalancing arms. ACE2 is a major player in the protective arm, highly expressed in lungs and gut with the ability to mitigate cardiopulmonary diseases such as inflammatory lung disease. ACE2 also exhibits activities involving gut microbiome, nutrition, and as a chaperone stabilizing the neutral amino acid transporter, B0AT1, in gut. But the current interest in ACE2 arises because it is the cell surface receptor for the novel coronavirus, severe acute respiratory syndrome coronavirus-2, to infect host cells, similar to severe acute respiratory syndrome coronavirus-2. This suggests that ACE2 be considered harmful, however, because of its important other roles, it is paradoxically a potential therapeutic target for cardiopulmonary diseases, including coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2. This review describes the discovery of ACE2, its physiological functions, and its place in the renin-angiotensin system. It illustrates new analyses of the structure of ACE2 that provides better understanding of its actions particularly in lung and gut, shedding of ACE2 by ADAM17 (a disintegrin and metallopeptidase domain 17 protein), and role of TMPRSS2 (transmembrane serine proteases 2) in severe acute respiratory syndrome coronavirus-2 entry into host cells. Cardiopulmonary diseases are associated with decreased ACE2 activity and the mitigation by increasing ACE2 activity along with its therapeutic relevance are addressed. Finally, the potential use of ACE2 as a treatment target in COVID-19, despite its role to allow viral entry into host cells, is suggested.
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PMID:ACE2 (Angiotensin-Converting Enzyme 2) in Cardiopulmonary Diseases: Ramifications for the Control of SARS-CoV-2. 3278 58

Angiotensin-converting enzyme 2 (ACE2) has been highlighted for its role as a receptor for SARS-CoV-2, responsible for the current COVID-19 pandemic. This review summarizes current knowledge about ACE2 as a multifunctional protein, focusing on its relevance in inflammatory bowel disease (IBD). As an enzyme, ACE2 may be protective in IBD because it favors the counter-regulatory arm of the renin-angiotensin system or deleterious because it metabolizes other anti-inflammatory/repairing elements. Meanwhile, as a receptor for SARS-CoV-2, the impact of ACE2 expression/activity on infection is still under debate because no direct evidence has been reported and, again, both protective and deleterious pathways are possible. Research has shown that ACE2 regulates the expression of the neutral amino acid transporter B0AT1, controlling tryptophan-associated intestinal inflammation and nutritional status. Finally, intact membrane-bound or shed soluble ACE2 can also trigger integrin signaling, modulating the response to anti-integrin biologic drugs used to treat IBD (such as vedolizumab) and fibrosis, a long-term complication of IBD. As such, future studies on ACE2 expression/activity in IBD can improve monitoring of the disease and explore an alternative pharmacological target.
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PMID:Unraveling the Role of ACE2, the Binding Receptor for SARS-CoV-2, in Inflammatory Bowel Disease. 3306 47

ACE2 is a type I membrane protein with extracellular carboxypeptidase activity displaying a broad tissue distribution with highest expression levels at the brush border membrane (BBM) of small intestine enterocytes and a lower expression in stomach and colon. In small intestinal mucosa, ACE2 mRNA expression appears to increase with age and to display higher levels in patients taking ACE-inhibitors (ACE-I). There, ACE2 protein heterodimerizes with the neutral amino acid transporter Broad neutral Amino acid Transporter 1 (B0AT1) (SLC6A19) or the imino acid transporter Sodium-dependent Imino Transporter 1 (SIT1) (SLC6A20), associations that are required for the surface expression of these transport proteins. These heterodimers can form quaternary structures able to function as binding sites for SARS-CoV-2 spike glycoproteins. The heterodimerization of the carboxypeptidase ACE2 with B0AT1 is suggested to favor the direct supply of substrate amino acids to the transporter, but whether this association impacts the ability of ACE2 to mediate viral infection is not known. B0AT1 mutations cause Hartnup disorder, a condition characterized by neutral aminoaciduria and, in some cases, pellagra-like symptoms, such as photosensitive rash, diarrhea, and cerebellar ataxia. Correspondingly, the lack of ACE2 and the concurrent absence of B0AT1 expression in small intestine causes a decrease in l-tryptophan absorption, niacin deficiency, decreased intestinal antimicrobial peptide production, and increased susceptibility to inflammatory bowel disease (IBD) in mice. Thus, the abundant expression of ACE2 in small intestine and its association with amino acid transporters appears to play a crucial role for the digestion of peptides and the absorption of amino acids and, thereby, for the maintenance of structural and functional gut integrity.
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PMID:ACE2 and gut amino acid transport. 3314 Aug 27