Review
Membrane-associated zinc peptidase families: comparing ACE and ACE2

https://doi.org/10.1016/j.bbapap.2004.10.010Get rights and content

Abstract

In contrast to the relatively ubiquitous angiotensin-converting enzyme (ACE), expression of the mammalian ACE homologue, ACE2, was initially described in the heart, kidney and testis. ACE2 is a type I integral membrane protein with its active site domain exposed to the extracellular surface of endothelial cells and the renal tubular epithelium. Here ACE2 is poised to metabolise circulating peptides which may include angiotensin II, a potent vasoconstrictor and the product of angiotensin I cleavage by ACE. To this end, ACE2 may counterbalance the effects of ACE within the renin–angiotensin system (RAS). Indeed, ACE2 has been implicated in the regulation of heart and renal function where it is proposed to control the levels of angiotensin II relative to its hypotensive metabolite, angiotensin-(1–7). The recent solution of the structure of ACE2, and ACE, has provided new insight into the substrate and inhibitor profiles of these two key regulators of the RAS. As the complexity of this crucial pathway is unravelled, there is a growing interest in the therapeutic potential of agents that modulate the activity of ACE2.

Abbreviations

ACE
angiotensin-converting enzyme
CP-A
carboxypeptidase-A
CoV
coronavirus
NEP
neutral endopeptidase/neprilysin
QTL
quantitative trait locus
RAS
renin–angiotensin system
SARS
severe acute respiratory syndrome
SNP
single nucleotide polymorphism
SHR
spontaneous hypertensive rat

Keywords

Metallopeptidase
Angiotensin
SARS
Coronavirus
Structure

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1

These authors contributed equally to the preparation of this manuscript.

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