Affordable Access

deepdyve-link
Publisher Website

Metabolism of angiotensin peptides by angiotensin converting enzyme 2 (ACE2) and analysis of the effect of excess zinc on ACE2 enzymatic activity.

Authors
  • Polak, Yasmin1
  • Speth, Robert C2
  • 1 College of Pharmacy, University of Utrecht, Universiteitsweg 99, 3584 CG, Utrecht, the Netherlands; College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, 33328, United States. Electronic address: [email protected] , (Netherlands)
  • 2 College of Pharmacy, University of Utrecht, Universiteitsweg 99, 3584 CG, Utrecht, the Netherlands; College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, 33328, United States. Electronic address: [email protected] , (Netherlands)
Type
Published Article
Journal
Peptides
Publication Date
Mar 01, 2021
Volume
137
Pages
170477–170477
Identifiers
DOI: 10.1016/j.peptides.2020.170477
PMID: 33400951
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

After decades of notoriety for its adverse cardiovascular, proinflammatory and profibrotic actions, the renin-angiotensin system (RAS) began to be cast in a more favorable light with the discovery of angiotensin-converting enzyme-2 (ACE2) in 2000. This monocarboxypeptidase, best known for its ability to metabolize angiotensin (Ang) II to Ang 1-7, counteracts the adverse effects of Ang II mediated by the AT1 Ang II receptor. Ang peptides are classically considered to be metabolized by aminopeptidases, by which the nomenclature Ang III (des-Asp1Ang II, 2-8 heptapeptide) and Ang IV (des-Asp1des-Arg2Ang II, 3-8 hexapeptide) are derived. This report compares the ability of recombinant human ACE2 (rhACE2) to metabolize Ang III, Ang IV and Ang V, (4-8 pentapeptide) relative to Ang II to form corresponding des-omega-Phe metabolites. rhACE2 has highest affinity (lowest Km) for Ang III, followed by Ang II ∼ Ang V, followed by Ang IV. However, rhACE2 has the highest Kcat for metabolising Ang IV followed by Ang V, Ang III and Ang II. The enzymatic efficiency (Kcat/Km) is highest for Ang V and Ang III followed by Ang IV and is lowest for Ang II. As a gluzincin metallopeptidase, ACE2 requires a zinc molecule at its active site for catalysis. This report also documents inhibition of ACE2 activity by concentrations of zinc exceeding 10 μM. These observations extend the functional significance of ACE2 to include the metabolic inactivation of Ang III, Ang IV and Ang V, reemphasizing the importance of monitoring zinc intake to maintain metabolic homeostasis. Copyright © 2021 Elsevier Inc. All rights reserved.

Report this publication

Statistics

Seen <100 times