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. 2019 Nov 6;9:16098. doi: 10.1038/s41598-019-52658-9

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Potential endogenous substrates of the enzymatic activities analyzed in the present work. Glutamyl aminopeptidase (GluAP, EC 3.4.11.7)) metabolizes Ang II to produce Ang III and also hydrolyzes cholecystokinin (CCK)¹⁶. Alanyl aminopeptidase (AlaAP, EC 3.4.11.2) metabolizes Ang III to form Ang IV¹³ and also acts as enkephalinase¹² regulating enkephalin (ENK) function. Cystinyl aminopeptidase (CysAP, EC 3.4.11.3) which has been reported to be the Ang IV receptor (AT₄)¹⁵ or the insulin-regulated aminopeptidase (IRAP), involved in cell glucose uptake¹⁵, also acts as oxytocinase and vasopressinase¹⁴ regulating oxytocin (OX) and vasopressin (antidiuretic hormone, ADH). Partial steps of the enzymatic cascade of the renin-angiotensin system (RAS) are represented in the diagram.