Studies of angiotensin I converting enzyme: effects of kinins, bacitracin, γ-aminobutyric and ε-aminocaproic acids, and related compounds on substrate binding and catalysis in vitro

1986 ◽  
Vol 64 (1) ◽  
pp. 50-54 ◽  
Author(s):  
Charles E. Odya ◽  
Ford P. Wilgis
Keyword(s):  
Inhibitory Concentration ◽  
Aminocaproic Acid ◽  
Aminobutyric Acid ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Angiotensin I Converting Enzyme ◽  
The Mean ◽  
Hydrolysis Of ◽  
Related Compounds

Bradykinin and 22 of its analogs were evaluated for their abilities to inhibit the hydrolysis of [3H]hippurylglycylglycine by purified porcine kidney angiotensin I converting enzyme. The mean inhibitory concentration (IC50) for bradykinin was 1.2 ± 0.2 × 10−6 M. Except for Ile-Ser-bradykinin and [Sar4]-bradykinin, none of the kinin analogs were more potent in this regard than bradykinin. Bacitracin, γ-aminobutyric acid, ε-aminocaproic acid, and structurally related compounds were also tested. The IC50 value for bacitracin was 1.9 ± 0.4 × 10−4 M, γ-aminobutyric acid, 83.4 ± 7.2 mM, and for ε-aminocaproic acid, 7.0 ± 1.4 mM. Compounds were also evaluated for their abilities to prevent 125I-labelled [Tyr1]-kallidin binding to angiotensin I converting enzyme inhibited by EDTA. The IC50 values for bradykinin, bacitracin, γ-aminobutyric acid, and ε-aminocaproic acid were 1.6 ± 0.3 × 10−8 M, 2.6 ± 0.9 × 10−6 M, >291 mM, and 13.2 ± 3.9 mM, respectively.

scholarly journals A novel peptide-processing activity of insect peptidyl-dipeptidase A (angiotensin I-converting enzyme): the hydrolysis of lysyl-arginine and arginyl-arginine from the C-terminus of an insect prohormone peptide

1998 ◽  
Vol 330 (1) ◽  
pp. 61-65 ◽  
Author(s):  
R. Elwyn ISAAC ◽  
Liliane SCHOOFS ◽  
A. Tracy WILLIAMS ◽  
Dirk VEELAERT ◽  
Mohammed SAJID ◽  
...  
Keyword(s):  
Neurosecretory Cells ◽  
Single Domain ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Recognition Sequence ◽  
Angiotensin I Converting Enzyme ◽  
C Terminus ◽  
Processing Activity ◽  
Hydrolysis Of

Insect peptidyl-dipeptidase A [angiotensin I-converting enzyme (ACE)] is a soluble single-domain peptidyl-dipeptidase that has many properties in common with the C-domain of mammalian somatic ACE and with the single-domain mammalian germinal ACE. Mammalian somatic ACE is important in blood homoeostasis, but the role of ACE in insects is not known. Immunocytochemistry has been used to localize ACE in the neuroendocrine system of the locust, Locusta migratoria. Staining was observed in five groups of neurosecretory cells in the brain and suboesophageal ganglion, in the nervi corpori cardiaci, the storage part of the corpora cardiaca and in the nervi corpori allati. In three groups of neurosecretory cells, ACE co-localized with locustamyotropins, suggesting a possible role for the enzyme in the metabolism of these neuropeptides. We demonstrate in vitro a novel activity of ACE that removes pairs of basic amino acid residues from a locustamyotropin peptide extended at the C-terminus with either Gly-Lys-Arg or Gly-Arg-Arg, corresponding to a consensus recognition sequence for endoproteolysis of prohormone proteins by prohormone convertases. The low Km and high kcat values (Km 7.3 and 5.0 μM, kcat 226 and 207 s-1 for the hydrolysis of Phe-Ser-Pro-Arg-Leu-Gly-Lys-Arg and Phe-Ser-Pro-Arg-Leu-Gly-Arg-Arg, respectively) obtained for the hydrolysis of these two peptides by insect ACE means that these peptides, along with mammalian bradykinin, are the most favoured in vitro ACE substrates so far identified. The discovery of this in vitro prohormone-processing activity of insect ACE provides a possible explanation for the intracellular co-localization of the enzyme with locustamyotropin peptides, and provides evidence for a new role for ACE in the biosynthesis of peptide hormones and transmitters.

Effects of γ-Aminobutyric Acid on the Erectogenic Properties of Sildenafil

2017 ◽  
Vol 9 (03) ◽  
Author(s):  
Adefegha S. A. ◽  
Oyeleye S. I. ◽  
Oboh G.
Keyword(s):  
Side Effects ◽  
Inhibitory Effect ◽  
Aminobutyric Acid ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Inhibiting Effect ◽  
Therapeutic Drugs ◽  
Angiotensin I Converting Enzyme ◽  
In Vitro Effects

Erectile dysfunction (ED) is a disorder of increasing socio-economic burden. Therapeutic drugs such as sildenafil have been in use for the treatment of ED, but with their associated side effects. γ-aminobutyric acid (GABA) is a neurotransmitter with possible vasodilatory properties. In this study, the effect of GABA on the erectogenic properties of sildenafil was investigated. Aqueous solution of GABA and sildenafil (1 mM) was separately prepared as well as the mixtures of both (75% GABA + 25% sildenafil; 50% GABA + 50% sildenafil; 25% GABA + 75% sildenafil). Thereafter, the in vitro effects of all the studied samples on the activities of arginase, angiotensin-I converting enzyme (ACE) and acetylcholinesterase (AChE) were investigated. The results revealed that all the samples inhibited arginase, ACE and AChE activities. Considering the various combinations, 25% GABA + 75% sildenafil had the highest arginase inhibitory effect, 50% GABA + 50% sildenafil showed the highest ACE inhibiting effect, while 25% GABA + 75% sildenafil exhibited the highest AChE inhibitory effect. Therefore, the observed enzyme inhibiting effect of sildenafil, GABA and their various combinations on rat penile arginase, ACE and AChE activities could be part of the mechanism by which they elicit their erectogenic properties. The various combinations could thus serve as therapeutic intervention for the management of ED with a possible reduction in the side effects associated with the use of sildenafil; nevertheless, the combination of 75% GABA with 25% sildenafil exhibited the highest erectogenic potential.

scholarly journals Multivesicular Liposomes for the Sustained Release of Angiotensin I-Converting Enzyme (ACE) Inhibitory Peptides from Peanuts: Design, Characterization, and In Vitro Evaluation

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1746 ◽  
Author(s):  
Ning Li ◽  
Aimin Shi ◽  
Qiang Wang ◽  
Guoquan Zhang
Keyword(s):  
Drug Delivery ◽  
Zeta Potential ◽  
Sustained Release ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Ace Inhibitory Activity ◽  
Angiotensin I Converting Enzyme ◽  
Release Drug ◽  
Ace Inhibitory

The multivesicular liposome (MVL) provides a potential delivery approach to avoid the destruction of the structure of drugs by digestive enzymes of the oral cavity and gastrointestinal system. It also serves as a sustained-release drug delivery system. In this study, we aimed to incorporate a water-soluble substance into MVLs to enhance sustained release, prevent the destruction of drugs, and to expound the function of different components and their mechanism. MVLs were prepared using the spherical packing model. The morphology, structure, size distribution, and zeta potential of MVLs were examined using an optical microscope (OM), confocal microscopy (CLSM), transmission electron cryomicroscope (cryo-EM) micrograph, a Master Sizer 2000, and a zeta sizer, respectively. The digestion experiment was conducted using a bionic mouse digestive system model in vitro. An in vitro release and releasing mechanism were investigated using a dialysis method. The average particle size, polydispersity index, zeta potential, and encapsulation efficiency are 47.6 nm, 1.880, −70.5 ± 2.88 mV, and 82.00 ± 0.25%, respectively. The studies on the controlled release in vitro shows that MVLs have excellent controlled release and outstanding thermal stability. The angiotensin I-converting enzyme (ACE) inhibitory activity of ACE-inhibitory peptide (AP)-MVLs decreased only 2.84% after oral administration, and ACE inhibitory activity decreased by 5.03% after passing through the stomach. Therefore, it could serve as a promising sustained-release drug delivery system.

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