scholarly journals Kinetic probes for inter-domain co-operation in human somatic angiotensin-converting enzyme

2005 ◽  
Vol 391 (3) ◽  
pp. 641-647 ◽  
Author(s):  
Olga E. Skirgello ◽  
Peter V. Binevski ◽  
Vladimir F. Pozdnev ◽  
Olga A. Kost
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Enzymatic Activity ◽  
Active Site ◽  
The Other ◽  
Converting Enzyme ◽  
Human Enzyme ◽  
Independent Functions ◽  
The Common ◽  
The Individual ◽  
Hydrolysis Of

s-ACE (the somatic form of angiotensin-converting enzyme) consists of two homologous domains (N- and C-domains), each bearing a catalytic site. Negative co-operativity between the two domains has been demonstrated for cow and pig ACEs. However, for the human enzyme there are conflicting reports in the literature: some suggest possible negative co-operativity between the domains, whereas others indicate independent functions of the domains within s-ACE. We demonstrate here that a 1:1 stoichiometry for the binding of the common ACE inhibitors, captopril and lisinopril, to human s-ACE is enough to abolish enzymatic activity towards FA {N-[3-(2-furyl)acryloyl]}-Phe-GlyGly, Cbz (benzyloxycarbonyl)-Phe-His-Leu or Hip (N-benzoylglycyl)-His-Leu. The kinetic parameters for the hydrolysis of seven tripeptide substrates by human s-ACE appeared to represent average values for parameters obtained for the individual N- and C-domains. Kinetic analysis of the simultaneous hydrolysis of two substrates, Hip-His-Leu (S1) and Cbz-Phe-His-Leu (S2), with a common product (His-Leu) by s-ACE at different values for the ratio of the initial concentrations of these substrates (i.e. σ=[S2]0/[S1]0) demonstrated competition of these substrates for binding to the s-ACE molecule, i.e. binding of a substrate at one active site makes the other site unavailable for either the same or a different substrate. Thus the two domains within human s-ACE exhibit strong negative co-operativity upon binding of common inhibitors and in the hydrolysis reactions of tripeptide substrates.

Angiotensin converting enzyme in brush-border membranes of avian small intestine

1988 ◽  
Vol 135 (1) ◽  
pp. 1-8
Author(s):  
B. R. Stevens ◽  
A. Fernandez ◽  
C. del Rio Martinez
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Brush Border ◽  
Physiological Role ◽  
Intestinal Epithelial ◽  
Converting Enzyme ◽  
Brush Border Membranes ◽  
Fluid Uptake ◽  
The Common ◽  
Kinetics Of ◽  
Hydrolysis Of

Angiotensin converting enzyme activity was identified in brush-border membranes purified from the small intestinal epithelium of the common grackle, Quiscalus quiscula. Angiotensin converting enzyme was enriched 20-fold in the membrane preparation, compared with intestinal epithelial cell scrapes, and was coenriched with the brush-border markers, alkaline phosphatase and aminopeptidase N. The kinetics of hydrolysis of N-[3-(2-furyl)acryloyl]-L-phenylalanylglycylglycine (FAPGG) gave a Vmax of 907 +/− 41 units g-1 and a Km of 55 +/− 6 mumol l-1. The avian intestinal angiotensin converting enzyme was inhibited by the antihypertensive drug, Ramipril, with a median inhibitory concentration (IC50) of 1 nmol l-1. In the light of previous studies on angiotensin converting enzyme in mammalian epithelia, these results may implicate a physiological role for angiotensin converting enzyme in regulating electrolyte and fluid uptake in bird small intestines.

scholarly journals Novel activity of angiotensin-converting enzyme. Hydrolysis of cholecystokinin and gastrin analogues with release of the amidated C-terminal dipeptide

1989 ◽  
Vol 262 (1) ◽  
pp. 125-130 ◽  
Author(s):  
P Dubreuil ◽  
P Fulcrand ◽  
M Rodriguez ◽  
H Fulcrand ◽  
J Laur ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Chloride Ion ◽  
Peptide Bond ◽  
Major Product ◽  
Enzyme Hydrolysis ◽  
Ion Concentration ◽  
Converting Enzyme ◽  
Rabbit Lung ◽  
Hydrolysis Of

ACE (angiotensin-converting enzyme; peptidyl dipeptidase A; EC 3.4.15.1), cleaves C-terminal dipeptides from active peptides containing a free C-terminus. We investigated the hydrolysis of cholecystokinin-8 [CCK-8; Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2] and of various gastrin analogues by purified rabbit lung ACE. Although these peptides are amidated at their C-terminal end, they were metabolized by ACE to several peptide fragments. These fragments were analysed by h.p.l.c., isolated and identified by comparison with synthetic fragments, and by amino acid analysis. The initial and major site of hydrolysis was the penultimate peptide bond, which generated a major product, the C-terminal amidated dipeptide Asp-Phe-NH2. As a secondary cleavage, ACE subsequently released di- or tri-peptides from the C-terminal end of the remaining N-terminal fragments. The cleavage of CCK-8 and gastrin analogues was inhibited by ACE inhibitors (Captopril and EDTA), but not by other enzyme inhibitors (phosphoramidon, thiorphan, bestatin etc.). Hydrolysis of [Leu15]gastrin-(14-17)-peptide [Boc (t-butoxycarbonyl)-Trp-Leu-Asp-Phe-NH2] in the presence of ACE was found to be dependent on the chloride-ion concentration. Km values for the hydrolysis of CCK-8, [Leu15]gastrin-(11-17)-peptide and Boc-[Leu15]gastrin-(14-17)-peptide at an NaCl concentration of 300 mM were respectively 115, 420 and 3280 microM, and the catalytic constants were about 33, 115 and 885 min-1. The kcat/Km for the reactions at 37 degrees C was approx. 0.28 microM-1.min-1, which is approx. 35 times less than that reported for the cleavage of angiotensin I. These results suggest that ACE might be involved in the metabolism in vivo of CCK and gastrin short fragments.

scholarly journals Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase

2002 ◽  
Vol 277 (17) ◽  
pp. 14838-14843 ◽  
Author(s):  
Chad Vickers ◽  
Paul Hales ◽  
Virendar Kaushik ◽  
Larry Dick ◽  
James Gavin ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Hydrolysis Of

Epidemics as Leisure Killers: The Transformation of Japan’s Entertainment Industry in the Second Half of the 19th Century

2021 ◽  
Vol 31 (1) ◽  
pp. 195-217
Keyword(s):  
19Th Century ◽  
Social Disorganization ◽  
The Other ◽  
Entertainment Industry ◽  
Economic Changes ◽  
The Past ◽  
The Common ◽  
The Individual ◽  
The 19Th Century

Among the various human attitudes toward a pandemic, along with fear, despair and anger, there is also an urge to praise the catastrophe or imbue it with some sort of hope. In 2020 such hopes were voiced in the stream of all the other COVID-19 reactions and interpretations in the form of predictions of imminent social, political or economic changes that may or must be brought on by the pandemic, or as calls to “rise above” the common human sentiment and see the pandemic as some sort of cruel-but-necessary bitter pill to cure human depravity or social disorganization. Is it really possible for a plague of any kind to be considered a relief? Or perhaps a just punishment? In order to assess the validity of such interpretations, this paper considers the artistic reactions to the pandemics of the past, specifically the images of the plague from Alexander Pushkin’s play Feast During the Plague, Antonin Artaud’s essay “The Theatre and the Plague” and Albert Camus’s novel The Plague. These works in different ways explore an attitude in which a plague can be praised in some respect. The plague can be a means of self-overcoming and purification for both an individual and for society. At the same time, Pushkin and Camus, each in his own way and by different means, show the illusory nature of that attitude. A mass catastrophe can reveal the resources already present in humankind, but it does not help either the individual or the society to progress.

DOCKING STUDY OF NOVEL N-SUBSTITUTED 2,5-BIS[(7-CHLOROQUINOLIN-4-YL)AMINO]PENTANOIC DERIVATIVES AS SELECTIVE HIGH-BINDER WITH ANGIOTENSIN CONVERTING ENZYME 2

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (08) ◽  
pp. 16-24
Author(s):  
Mohammed Oday Ezzat ◽  
Basma M. Abd Razik ◽  
Kutayba F. Dawood
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Active Site ◽  
Docking Study ◽  
World Health ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Pharmaceutical Properties ◽  
Novel Coronavirus

The prevalence of a novel coronavirus (2019-nCoV) in the last few months represents a serious threat as a world health emergency concern. Angiotensin-converting enzyme 2 (ACE2) is the host cellular receptor for the respiratory syndrome of coronavirus epidemic in 2019 (2019-nCoV). In this work, the active site of ACE2 is successfully located by Sitmap prediction tool and validated by different marketed drugs. To design and discover new medical countermeasure drugs, we evaluate a total of 184 molecules of 7-chloro-N-methylquinolin-4-amine derivatives for binding affinity inside the crystal structure of ACE2 located active site. A novel series of N-substituted 2,5-bis[(7-chloroquinolin-4-yl)amino]pentanoic acid derivatives is generated and evaluated for a prospect as a lead compound for (2019-nCoV) medication with a docking score range of (-10.60 to -8.99) kcal/mol for the highest twenty derivatives. Moreover, the ADME pharmaceutical properties were evaluated for further proposed experimental evaluation in vitro or in vivo

Effects of gas composition and pH on kinetics of lung angiotensin-converting enzyme

1987 ◽  
Vol 62 (3) ◽  
pp. 1216-1221 ◽  
Author(s):  
D. A. Rickaby ◽  
R. D. Bongard ◽  
M. J. Tristani ◽  
J. H. Linehan ◽  
C. A. Dawson
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Surface Area ◽  
Ph Dependence ◽  
Gas Composition ◽  
Converting Enzyme ◽  
Hydrolysis Process ◽  
Hypoxic Vasoconstriction ◽  
Ace Activity ◽  
Kinetics Of ◽  
Hydrolysis Of

Given the pH dependence of enzymes in general and the potential importance of a blood and alveolar gas composition dependency on the interpretation of changes in the hydrolysis of angiotensin-converting enzyme (ACE) substrates by pulmonary endothelial ACE, we examined the influence of Pco2 and Po2 on the hydrolysis of a synthetic ACE substrate (benzoyl-phenylalanyl-alanyl-proline, BPAP) on passage through isolated rabbit lungs. Perfusate pH values of about 7.1, 7.4, and 7.9 were obtained by ventilating the lungs with gas containing different CO2 concentrations and Po2 values of approximately 110 and approximately 10 Torr were obtained by varying the concentration of O2 in the ventilating gas mixture. In the range studied neither acidosis nor alkalosis produced any significant changes in BPAP hydrolysis or in the kinetic parameters, Vmax and Km, for the hydrolysis process. On the other hand, a reduction in BPAP hydrolysis was detected when the Po2 was reduced from 110 to 10 Torr. The Vmax for BPAP hydrolysis by the lung was inversely correlated with the magnitude of the hypoxic vasoconstriction that occurred, suggesting that the reduced BPAP hydrolysis with hypoxia was due to the loss of perfused surface area due to the vasoconstriction. The results suggest that correlations between Pco2 and/or pH and whole-lung ACE activity that might occur in diseased lungs do not imply causalty. The hemodynamic consequences of changing Po2 (i.e., hypoxic vasoconstriction) may alter whole-organ ACE activity in the sense of changing the perfused surface area (i.e., the amount of ACE in contact with flowing perfusate).

Hydrolysis of a synthetic angiotensin-converting enzyme substrate in dog lungs

1989 ◽  
Vol 257 (6) ◽  
pp. H2006-H2016
Author(s):  
J. H. Linehan ◽  
T. A. Bronikowski ◽  
D. A. Rickaby ◽  
C. A. Dawson
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Flow Rate ◽  
Dilution Method ◽  
Converting Enzyme ◽  
Pulmonary Endothelium ◽  
Multiple Indicator Dilution ◽  
Enzyme Substrate ◽  
Multiple Indicator ◽  
Pass Through ◽  
Hydrolysis Of

The present study was carried out to begin to evaluate the saturable kinetics of the hydrolysis of a synthetic substrate, benzoyl-phenylalanyl-alanyl-proline (BPAP), for angiotensin-converting enzyme (ACE), by the pulmonary endothelium of the dog using a multiple indicator dilution method. In the experiments, isolated dog lung lobes were perfused with a salt solution containing 5% bovine serum albumin. Boluses containing [3H]BPAP, and various amounts of unlabeled BPAP were injected into the lobar artery, and timed samples of venous effluent were collected. The samples were analyzed to determine the fractional hydrolysis of the injected BPAP. The BPAP hydrolysis on passage through the lungs exhibited the saturable behavior and the relative insensitivity to changing flow rate previously described. Since we have described previously that BPAP behaves as if it exists in two forms, one of which is virtually unhydrolyzable on a single pass through the lungs, a model was formulated to include the influence of the unhydrolyzable form, as well as the saturable hydrolysis of the hydrolyzable form, on the fractional hydrolysis of the injected BPAP. This model provides a new method for estimating the kinetic parameters of BPAP hydrolysis by pulmonary endothelial ACE, and it explains the observation that the fractional BPAP hydrolysis does not vary with flow rate and transit time to the extent predicted by previous models.

scholarly journals Inhibitory Activities of Polyphenolic Extracts of Bangladeshi Vegetables against α-Amylase, α-Glucosidase, Pancreatic Lipase, Renin, and Angiotensin-Converting Enzyme

Foods ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 844
Author(s):  
Razia Sultana ◽  
Adeola M. Alashi ◽  
Khaleda Islam ◽  
Md Saifullah ◽  
C. Emdad Haque ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Pancreatic Lipase ◽  
Lipase Activity ◽  
Inhibitory Activity ◽  
The Other ◽  
Converting Enzyme ◽  
Inhibitory Activities ◽  
Ash Gourd ◽  
Better Than

The aim of the study was to determine the in vitro enzyme inhibition activities of aqueous polyphenolic extracts of nine popular Bangladeshi vegetables, namely ash gourd, bitter gourd, brinjal, Indian spinach, kangkong, okra, ridge gourd, snake gourd, and stem amaranth. Polyphenolic glycosides were the major compounds present in the extracts. Inhibition of α-amylase (up to 100% at 1 mg/mL) was stronger than α-glucosidase inhibition (up to 70.78% at 10 mg/mL). The Indian spinach extract was the strongest inhibitor of pancreatic lipase activity (IC50 = 276.77 µg/mL), which was significantly better than that of orlistat (381.16 µg/mL), a drug. Ash gourd (76.51%), brinjal (72.48%), and snake gourd (66.82%) extracts were the most effective inhibitors of angiotensin-converting enzyme (ACE), an enzyme whose excessive activities have been associated with hypertension. Brinjal also had a significantly higher renin-inhibitory activity than the other vegetable extracts. We conclude that the vegetable extracts may have the ability to reduce enzyme activities that have been associated with hyperglycemia, hyperlipidemia, and hypertension.

scholarly journals Hydrolysis of rat melanin-concentrating hormone by endopeptidase 24.11 (neutral endopeptidase)

1992 ◽  
Vol 286 (1) ◽  
pp. 217-221 ◽  
Author(s):  
F Checler ◽  
P Dauch ◽  
H Barelli ◽  
J L Nahon ◽  
J P Vincent
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Cyclic Peptide ◽  
Degradation Products ◽  
Neutral Endopeptidase ◽  
Converting Enzyme ◽  
Carboxypeptidase A ◽  
Disulphide Bridge ◽  
Melanocyte Stimulating Hormone ◽  
Melanin Concentrating Hormone ◽  
Hydrolysis Of

Melanin-concentrating hormone (MCH) is a cyclic peptide which behaves as an antagonist of the pituitary melanotropic hormone alpha-melanocyte-stimulating hormone in fishes. Cloning of the rat MCH cDNA precursor recently revealed the presence of an additional putative peptide named NEI. The present work examined the susceptibility of these novel peptides to hydrolysis by various purified exo- and endo-peptidases including endopeptidases 24.11 (NEP), 24.15, 24.16, angiotensin-converting enzyme, leucine aminopeptidase and carboxypeptidase A. NEP attacked MCH at three sites of the molecule with an apparent affinity of about 12 microM and a kcat. of 4 min-1. The first site of cleavage was at Cys-7-Met-8, i.e. within the peptide loop formed by the internal disulphide bridge. NEP could therefore be considered as an MCH-inactivating peptidase since the degradation products generated are probably devoid of biological activity. In contrast, NEI neither inhibited the degradation of the NEP chromogenic substrate glutaryl-Phe-Ala-Phe-p-aminobenzoate nor was susceptible to proteolysis by NEP. Unlike NEP, angiotensin-converting enzyme, endopeptidase 24.15 and endopeptidase 24.16 appeared totally unable to cleave MCH, whereas the peptide was readily degraded by aminopeptidase M and carboxypeptidase A.

Sign in / Sign up

Export Citation Format

Share Document