Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been reported to improve insulin sensitivity. However, despite extensive investigation, the mechanisms responsible for this effect are not fully understood. Reduction of plasma angiotensin II and inhibition of kininase II have been suggested to contribute to improve insulin sensitivity. Insulin binding was measured at tracer insulin concentration in intact cells with or without captopril treatment. Specific binding, expressed as percent of total insulin added, was not different in control and captopril-treated cells. However, captopril treatment caused an increase in insulin-induced insulin receptor substrate-1 (IRS-1) phosphorylation accompanied by an increased association of IRS-1 with phosphoinositide-3 kinase (PI-3 kinase), despite no change on insulin receptor (IR) autophosphorylation. There was also an increased threonine kinase B (AKT) phosphorylation in captopril-treated cells followed by enhanced basal and insulin-stimulated glucose uptake. These results indicate that captopril treatment has a direct effect on early phosphorylation events induced by insulin in BC3H-1 myocytes.
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PMID:Evidence for a direct effect of captopril on early steps of insulin action in BC3H-1 myocytes. 1264 62

The degradation of the unblocked hexapeptide, trypsin modulating oostatic factor of the flesh fly Neobellieria (Sarcophaga) bullata (Neb-TMOF) was studied in vitro in the hemolymph of the lepidopteran Spodoptera frugiperda, the orthopteran Schistocerca gregaria and the dictyopteran Leucophaea maderae. The half-life in the different species varied from approximately 3min in L. maderae to approximately 25min in S. gregaria. Purification of the degradation products and ESI-Qq-oa-Tof mass spectrometry revealed the fragments Asn-Pro-Thr-Asn, Leu-His and Asn-Pro, which were the same in the hemolymph of all species. Except in Leucophaea, Neb-TMOF was cleaved in dipeptides starting from the C-terminus and the reaction could be, at least partially, inhibited by captopril. These observations suggest that a dipeptidase, which has very similar enzymatic properties as mammalian angiotensin converting enzyme (ACE) and which circulates in the hemolymph, apparently is involved in the breakdown of Neb-TMOF and might be a common but not a universal enzyme in insect hemolymph.The introduction of Neb-TMOF into the gut of S. gregaria with the help of a capillary tube (intubation) demonstrated that the intact peptide is able to cross the gut epithelium and to appear in the hemolymph compartment. Since [3H]-inulin, which is too large to cross cell membranes, was found to penetrate the gut walls at a measurable rate, the paracellular pathway might be also permeable to smaller peptides. There was indeed a clear correlation between the molecular weight of inulin, Neb-TMOF, and inositol and the rate of penetration of these compounds through the gut epithelium to the hemolymph. These are promising findings in view of a potential use of such peptides for insect control purposes.
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PMID:Proteolytic breakdown of the Neb-trypsin modulating oostatic factor (Neb-TMOF) in the hemolymph of different insects and its gut epithelial transport. 1277 Jan 74

The homozygous deletion allele of the angiotensin-converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the epsilon4 allele of the apolipoprotein E gene (apoE/epsilon4) are reported to be associated with ischemic heart disease. Cerebral infarction (CI) is another atherosclerotic disease, and the effects of these polymorphisms on CI have been confusing. The frequency of the DD genotype of the ACE gene, but not the TT genotype of the AGN gene and the epsilon4 allele of ApoE, was significantly higher in subjects with than those without CI in Japan. In this study, we investigated whether ACE/DD, AGN/TT, and apoE/epsilon4 genotypes are associated with CI and whether genetic risk is enhanced by the effect of one upon another. We ascertained these genotypes in patients with CI (n = 365), diagnosed by brain computed tomography. Control subjects for the infarction group were randomly selected from 319 subjects matched for age, gender, and history of hypertension with patients. The ACE/DD genotype was not associated with CI. Frequency of the AGN/TT genotype was higher in patients with CI than in controls (chi2 = 12.287, p < 0.05). The frequency of t allele was 0.88 in patients and 0.82 in controls (chi2 = 11.041, p < 0.05; odds ratio, 1.7). Furthermore, the AGN/TT genotype increased the relative risk for CI in subjects with the ACE/DD genotype (chi2 = 7.8, p < 0.05; odds ratio, 1.9). There was no significant association between apoE/epsilon4 and CI. These results suggest that AGN/TT predicts CI and ACE/DD enhances the risk for CI associated with AGN/TT in a Korean population.
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PMID:Polymorphism of angiotensin-converting enzyme, angiotensinogen, and apolipoprotein E genes in Korean patients with cerebral infarction. 1450 Sep 90

Sasang constitutional medicine is a major branch of Korean traditional Oriental medicine. The differences of disease susceptibility to be shown in Sasang constitution may be due to genetic factors. Therefore, the authors examined relationship between candidate genes of cerebral infarction (CI) and Sasang constitution. The homozygous deletion allele of the angiotensin converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the e4 allele of the apolipoprotein E gene (ApoE/e4) are reported to be associated with ischemic heart disease. CI is another atherosclerotic disease; and the effects of these polymorphisms on CI have been confusing. This study investigated whether ACE/DD, AGN/TT, and ApoE/e4 genotypes are associated with CI and whether genetic risk is enhanced by Sasang constitutional classification. The authors ascertained these genotypes in patients with CI (N=211), diagnosed by brain computed tomography. Control subjects for the infarction group were randomly selected from 319 subjects matched for age, sex, and history of hypertension with patients. The ACE/DD genotype was not associated with CI. However, there was significant association between ApoE polymorphism and CI (chi2=15.089, p<.05). Furthermore, frequency of AGN/TT genotype was higher in the patients with CI than in the controls (chi2=20.072, p<.05). The frequency of T allele was 0.91 in patients and 0.82 in controls (chi2=17.237, p<.05). However, Sasang constitutional classification did not increase the relative risk for CI in the subjects with ApoE/e4 or AGN/T allele. These results suggest that ApoE and AGN polymorphism predict CI, but Sasang constitutional classification does not enhance the risk for CI associated with ApoE/e4 or AGN/TT in a Korean population.
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PMID:Candidate genes of cerebral infarction and traditional classification in Koreans with cerebral infarction. 1601 71

In a previous study, we isolated the inhibitory peptide (P4 peptide, Gly-Phe-Hyp-Gly-Thr-Hyp-Gly-Leu-Hyp-Gly-Phe) for angiotensin I-converting enzyme (ACE) from chicken breast muscle extract possessing hypotensive activity for spontaneously hypertensive rats (SHRs). This study was performed to elucidate the peptide's action mechanisms of inhibiting ACE. Intravenous administration of synthetic P4 peptide resulted in significant drops in the blood pressures of SHRs. As Dixon plots indicate, the P4 peptide showed high affinity toward ACE (K(i) = 11.48 microM) and only 10% of the total amount of the P4 peptide was decomposed. The analyses of the relationship between the ACE inhibitory activity and structure of the P4 peptide clarified that Hyp-Gly-Leu-Hyp-Gly-Phe showed a stronger activity (IC50 = 10 microM) than the P4 peptide (IC50 = 46 microM). When Phe at the C-terminus of the P4 peptide was deleted, IC50 changed to 25000 microM, indicating that Phe at the C-terminus of the peptide is very important for ACE inhibitory activity.
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PMID:Action mechanism of an angiotensin I-converting enzyme inhibitory peptide derived from chicken breast muscle. 1644 6

Mung bean protein isolates were hydrolyzed for 2 h by Alcalase. The generated hydrolysate showed angiotensin I-converting enzyme (ACE) inhibitory activity with the IC(50) value of 0.64 mg protein/ml. Three kinds of novel ACE inhibitory peptides were isolated from the hydrolysate by Sephadex G-15 and reverse-phase high performance liquid chromatography (RP-HPLC). These peptides were identified by amino acid composition analysis and matrix assisted-laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF MS/MS), as Lys-Asp-Tyr-Arg-Leu, Val-Thr-Pro-Ala-Leu-Arg and Lys-Leu-Pro-Ala-Gly-Thr-Leu-Phe with the IC(50) values of 26.5 microM, 82.4 microM and 13.4 microM, respectively.
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PMID:Novel angiotensin I-converting enzyme inhibitory peptides isolated from Alcalase hydrolysate of mung bean protein. 1668 Jul 98

The izumi shrimp (Plesionika izumiae Omori, 1971) is an unused resource which can be caught off the southern coast of Tokushima Prefecture. We have previously found that an izumi shrimp hydrolysate significantly inhibited the age-associated spontaneous increase in blood pressure in stroke-prone spontaneously hypertensive rats. In this present study, two angiotensin I-converting enzyme inhibitory peptides were isolated from an izumi shrimp hydrolysate by using high-performance liquid chromatography, and their amino acid sequences were determined to be Val-Trp-Tyr-His-Thr and Val-Trp. A single oral administration of synthetic Val-Trp-Tyr-His-Thr or Val-Trp significantly decreased the blood pressure in stroke-prone spontaneously hypertensive rats. The antigenicity and allergenicity of the izumi shrimp hydrolysate against BALB/c mice were very low. These results demonstrate that the angiotensin I-converting enzyme inhibitory peptides isolated from the izumi shrimp hydrolysate had an anti-hypertensive effect on rats.
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PMID:Determination of antihypertensive peptides from an izumi shrimp hydrolysate. 1832 50

Although LC-MS methods are increasingly used for the absolute quantification of proteins, the lack of appropriate internal standard (IS) hinders the development of rapid and standardized analytical methods for both in vitro and in vivo studies. Here, we have developed a novel method for the absolute quantification of a therapeutic protein, which is monoclonal antibody (mAb). The method combines liquid chromatography tandem mass spectrometry (LC-MS/MS) and protein cleavage isotope dilution mass spectrometry with the isotope-labeled mAb as IS. The latter was identical to the analyzed mAb with the exception that each threonine contains four (13)C atoms and one (15)N atom. Serum samples were spiked with IS prior to the overnight trypsin digestion and subsequent sample cleanup. Sample extracts were analyzed on a C18 ACE column (150 mm x 4.6 mm) using an LC gradient time of 11 min. Endogenous mAb concentrations were determined by calculating the peak height ratio of its signature peptide to the corresponding isotope-labeled peptide. The linear dynamic range was established between 5.00 and 1000 microg/mL mAb with accuracy and precision within +/-15% at all concentrations and below +/-20% at the LLOQ (lower limit of quantification). The overall method recovery in terms of mAb was 14%. The losses due to sample preparation (digestion and purification) were 72% from which about 32% was due to the first step of the method, the sample digestion. This huge loss during sample preparation strongly emphasizes the necessity to employ an IS right from the beginning. Our method was successfully applied to the mAb quantification in marmoset serum study samples, and the precision obtained on duplicate samples was, in most cases, below 20%. The comparison with enzyme-linked immunosorbent assay (ELISA) showed higher exposure in terms of AUC and Cmax with the LC-MS/MS method. Possible reasons for this discrepancy are discussed in this study. The results of this study indicate that our LC-MS/MS method is a simple, rapid, and precise approach for the therapeutic mAb quantification to support preclinical and clinical studies.
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PMID:Towards absolute quantification of therapeutic monoclonal antibody in serum by LC-MS/MS using isotope-labeled antibody standard and protein cleavage isotope dilution mass spectrometry. 1846 83

Acetes chinensis is an underutilized shrimp species thriving in Bo Hai Gulf of China. Its hydrolysate digested with protease SM98011 has been previously shown to have high angiotensin I-converting enzyme (ACE) inhibitory activity (He et al., J Pept Sci 12:726-733, 2006). In this article, A. chinensis were fermented by Lactobacillus fermentum SM 605 and the fermented sauce presented high ACE inhibitory activity. The minimum IC(50) value (3.37 +/- 0.04 mg/mL) was achieved by response surface methodology with optimized process parameters such as fermentation time of 24.19 h, incubation temperature at 38.10 degrees C, and pH 6.12. Three ACE inhibitory peptides are purified by ultrafiltration, gel filtration, and reverse-phase high performance liquid chromatography. Identified by mass spectrometry, their amino acid sequences are Asp-Pro, Gly-Thr-Gly, and Ser-Thr, with IC(50) values of 2.15 +/- 0.02, 5.54 +/- 0.09, and 4.03 +/- 0.10 microM, respectively. Also, they are all novel ACE inhibitory peptides. Compared with protease digestion, fermentation is a simpler and cheaper method to produce ACE inhibitory peptides from shrimp A. chinensis.
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PMID:Production of novel angiotensin I-converting enzyme inhibitory peptides by fermentation of marine shrimp Acetes chinensis with Lactobacillus fermentum SM 605. 1852 93

Egg proteins are an excellent source of bioactive peptides. The purpose of this work was to study the effect of cooking methods on the production of angiotensin converting enzyme (ACE) inhibitory peptides. Boiled or fried eggs (in the forms of whites, yolks, and whole eggs) were digested by gastrointestinal tract proteases at simulated gut conditions. Fried egg digests showed more potent activity than those of boiled egg digests; the fried whole egg digest had an IC(50) value of 0.009 mg protein/mL. This hydrolysate was further purified by cation exchange chromatography and gel filtration chromatography. Seven peptides, Val-Asp-Phe (IC(50): 6.59 microM), Leu-Pro-Phe (10.59 microM), Met-Pro-Phe (17.98 microM), Tyr-Thr-Ala-Gly-Val (23.38 microM), Glu-Arg-Tyr-Pro-Ile (8.76 microM), Ile-Pro-Phe (8.78 microM), and Thr-Thr-Ile (24.94 microM), were identified by liquid chromatography-mass spectrometry (LC-MS/MS), and their IC(50) values were predicted by using our previously reported structure and activity models. The presence of several tripeptides from in vitro simulated gastrointestinal egg digest indicates that these peptides may be absorbed into the body and exert an in vivo antihypertensive activity, although in vivo study is needed to confirm this assumption. Our results showed that in vitro digestion of cooked eggs could generate a number of potent ACE inhibitory peptides which may have implications for cardiovascular disease prevention, including hypertension.
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PMID:Angiotensin I converting enzyme inhibitory peptides from simulated in vitro gastrointestinal digestion of cooked eggs. 1915 60


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