Evidence map›Paper›PMID 15283675›Full record

ArticleThe Biochemical journal2004

Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism.

Gillian I Rice, Daniel A Thomas, Peter J Grant, Anthony J Turner, Nigel M Hooper

Open access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The Biochemical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 321 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
321citing papers in PubMed, 2 pooled it
8.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

321 citing papers in PubMed, 2 syntheses or guidelines pooled it, 623 citations in OpenAlex.

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261 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Gillian I RiceProteolysis Research Group, School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, UK.
Daniel A Thomas
Peter J Grant
Anthony J Turner
Nigel M Hooper
University of Leeds · GBLeeds General Infirmary · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In the RAS (renin-angiotensin system), Ang I (angiotensin I) is cleaved by ACE (angiotensin-converting enzyme) to form Ang II (angiotensin II), which has effects on blood pressure, fluid and electrolyte homoeostasis. We have examined the kinetics of angiotensin peptide cleavage by full-length human ACE, the separate N- and C-domains of ACE, the homologue of ACE, ACE2, and NEP (neprilysin). The activity of the enzyme preparations was determined by active-site titrations using competitive tight-binding inhibitors and fluorogenic substrates. Ang I was effectively cleaved by NEP to Ang (1-7) (kcat/K(m) of 6.2x10(5) M(-1) x s(-1)), but was a poor substrate for ACE2 (kcat/K(m) of 3.3x10(4) M(-1) x s(-1)). Ang (1-9) was a better substrate for NEP than ACE (kcat/K(m) of 3.7x10(5) M(-1) x s(-1) compared with kcat/K(m) of 6.8x10(4) M(-1) x s(-1)). Ang II was cleaved efficiently by ACE2 to Ang (1-7) (kcat/K(m) of 2.2x10(6) M(-1) x s(-1)) and was cleaved by NEP (kcat/K(m) of 2.2x10(5) M(-1) x s(-1)) to several degradation products. In contrast with a previous report, Ang (1-7), like Ang I and Ang (1-9), was cleaved with a similar efficiency by both the N- and C-domains of ACE (kcat/K(m) of 3.6x10(5) M(-1) x s(-1) compared with kcat/K(m) of 3.3x10(5) M(-1) x s(-1)). The two active sites of ACE exhibited negative co-operativity when either Ang I or Ang (1-7) was the substrate. In addition, a range of ACE inhibitors failed to inhibit ACE2. These kinetic data highlight that the flux of peptides through the RAS is complex, with the levels of ACE, ACE2 and NEP dictating whether vasoconstriction or vasodilation will predominate.

Indexed as

Angiotensin-Converting Enzyme 2Angiotensin-Converting Enzyme InhibitorsAngiotensin IAngiotensin IIAngiotensinsAnimalsBinding SitesCarboxypeptidasesCHO CellsCricetinaeCricetulusHumansHydrolysisKineticsNeprilysinPeptide FragmentsACE2 protein, humanAngiotensin-Converting Enzyme 2Angiotensin-Converting Enzyme InhibitorsAngiotensin Iangiotensin I (1-7)Angiotensin IIAngiotensinsCarboxypeptidasesNeprilysinPeptide FragmentsPeptidyl-Dipeptidase A

Identifiers

PMID15283675
PMCPMC1134042
OpenAlexW2129053556

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.