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:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Angiotensin I-converting enzyme (EC 3.4.15.1) has been purified to electrophoretic homogeneity from chicken lung by using a facile two-step protocol which included affinity chromatography on Sepharose-bound captopril. 2. Captopril was a potent inhibitor of chicken lung angiotensin I-converting enzyme with Ki values of 2.0 nmol/l and 1.6 nmol/l for detergent-extracted and trypsin-extracted angiotensin I-converting enzymes, respectively. 3. Molecular weight comparison of trypsin-extracted (M(r)270,000) and detergent-extracted (M(r)690,000) angiotensin I-converting enzyme indicated that membrane-binding sequence contributed to a large extent to the enzyme molecule. 4. Kinetic properties of both forms of the enzyme suggested that the membrane-bound sequence contributed to an increase of the enzyme-substrate affinity.
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PMID:Inhibition and affinity chromatography of chicken lung angiotensin I-converting enzyme with captopril. 132 42

Isoelectric species of renin are physically heterogeneous. Recent evidence suggests that they may differ functionally, with some species producing natriuresis and diuresis, whereas others have no effect. A physiological function of secreted prorenin has not been documented in any species. The present study was designed to confirm and describe for the first time the renal effects of certain isoelectric species of prorenin. Anesthetized Sprague-Dawley rats were injected (0.1 ml) with trypsin-activated or nonactivated prorenin obtained from human ovarian follicular fluid. The dose chosen was calculated as sufficient to produce 2,300 ng angiotensin I.h-1.100 g rat body wt-1 in the presence of excess sheep substrate. Blood pressure, creatinine clearance, urine flow rate, and urine sodium, potassium, and osmolar excretion were measured. Activated prorenin from isoelectric peaks at isoelectric points (pI) 5.1, 5.2, 5.4, and 5.6 produced marked increases in urine volume (sixfold) and sodium excretion (7- to 10-fold) compared with the group receiving the vehicle (1% albumin in 0.9% saline). Activated prorenin from peaks at pI 4.9 and 5.8 produced no significant increase over the vehicle-only experiments. Captopril pretreatment (1 mg/kg iv) completely blocked the effects of peaks at pI 5.4 and 5.6. Interestingly, injection of nonactivated prorenin from peaks at pI 5.4 and 5.6 produced effects similar to the injection of activated prorenin from these peaks. Similarly, this effect was blocked by pretreatment with captopril. In summary, only certain isoelectric peaks of human prorenin whether activated, to active renin, or nonactivated produced a marked natriuresis and diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differing renal effects of activated and nonactivated isoelectric peaks of human prorenin in rats. 175 May 22

Using a high performance liquid chromatography assay that detects the cleavage of the C-terminal leucine from angiotensin I, we have identified a carboxypeptidase activity in mast cells from human lung and in dispersed mast cell preparations from human skin. The enzyme activity was detected in a preparation of dispersed human mast cells from lung of greater than 99% purity and was released with histamine after stimulation with goat anti-human IgE. In nine preparations of dispersed human mast cells from lung of 10 to 99% purity, net percentage of release of carboxypeptidase correlated with the release of histamine, localizing carboxypeptidase to mast cell secretory granules. The enzyme activity was also detected in preparations of dispersed human mast cells from skin and in extracts of whole skin. The inhibitor profile and m.w. of carboxypeptidase activity from preparations of dispersed mast cells from skin was similar to that from dispersed mast cells from lung. Mast cell carboxypeptidase had a m.w. on gel filtration of 30,000 to 35,000. The enzyme in crude lysates of dispersed mast cell preparations had optimal activity between pH 8.5 and 9.5 and was inhibited by potato inhibitor, which distinguished it from carboxypeptidase in cultured human foreskin keratinocytes and adult fibroblasts, and from other proteolytic mast cell enzymes. The enzyme activity was also inhibited by EDTA, o-phenanthroline, and, to a small extent, by 8-OH quinoline, but not by Captopril, soybean trypsin inhibitor, or pepstatin. These findings demonstrate that human mast cell secretory granules contain carboxypeptidase in addition to tryptase and chymase. It appears that mast cells from skin may have a higher content of carboxypeptidase than do mast cells from lung.
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PMID:Detection and partial characterization of a human mast cell carboxypeptidase. 244 71

The mechanism of bradykinin-potentiating activity of [des-Proline3]-bradykinin, a kinin originally generated from human plasma protein by trypsin, was studied in terms of its inhibitory actions on angiotensin-converting enzyme and kininase II prepared from rat lung. The results were compared with those obtained with Captopril. [Des-Pro3]-bradykinin was found to have a potent inhibitory action against angiotensin-converting enzyme with a K1 of 4.5 X 10(-12) M, which is approximately 7 times more potent than Captopril. It was also inhibitory to kininase II with a Ki of 4 X 10(-11) M, which is approximately 2,300-fold more potent than Captopril. The pattern of inhibition was purely competitive with increased apparent Km but no change in apparent Vmax for both angiotensin-converting enzyme and kininase II. This is in contrast to Captopril, which showed a mixed competitive and non-competitive type of inhibition with increased apparent Km and decreased Vmax for both enzymes. Such a potent inhibitory activity of [des-Pro3]-bradykinin or Arg-Pro-Gly-Phe-Ser-Pro-Phe-Arg is noteworthy, and accordingly we propose the name "converstatin" for this peptide.
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PMID:Potent inhibition of angiotensin-converting enzyme by [des-Pro3]-bradykinin or "converstatin" in comparison with Captopril. 300 38

We have used a high performance liquid chromatography assay, which detects chymotryptic cleavage of the phe8-his9 bond of angiotensin I to yield angiotensin II, in order to examine human lung mast cells for the presence of chymotryptic activity. Mast cells, purified from human lung by enzymatic dispersion, countercurrent elutriation, and Percoll gradient centrifugation, were lysed or challenged with goat anti-human IgE. In multiple experiments angiotensin II-converting activity was detected in lysates of 10-99% pure mast cell preparations. Regression analysis of net percent release values of histamine and the angiotensin I-converting activity from dose-response experiments demonstrated a correlation between the two parameters, indicating that the chymotrypsin-like enzyme is a constituent of the mast cell secretory granule. The chymotryptic activity was completely inhibited by 10(-3) M phenylmethylsulfonylfluoride but not by 10(-3) M Captopril, and the pH optimum of activity was 7.5-9.5. Gel filtration of released material separated the activity from tryptase and demonstrated an approximate molecular weight of 30-35,000. The mast cell enzyme, like a human skin chymotrypsin-like proteinase, can be distinguished from leukocyte cathepsin G by lack of susceptibility to inhibition by bovine pancreatic trypsin inhibitor. Thus, an enzyme with limited chymotryptic specificity is present in human lung mast cells. The Michaelis constant of the enzyme for angiotensin I of 6.0 X 10(-5) M is similar to that of endothelial cell angiotensin-converting enzyme and is consistent with a reaction of physiologic importance.
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PMID:A human lung mast cell chymotrypsin-like enzyme. Identification and partial characterization. 351 Oct 89

Midgut extracts from Aedes aegypti females exhibited hydrolytic activities against synthetic substrates for carboxypeptidase A, carboxyopeptidase B and leucine-aminopeptidase. The three activities showed a broad pH optimum, with maximum activities at pH between 6.5 and 8.5. Enzymatic activities were further characterized by testing the effects of a variety of protease inhibitors. Captopril and 1-10-phenantroline inhibited the activities of carboxypeptidases A and B, while leuhistin, amastatin and bestatin inhibited aminopeptidase activity. Exopeptidase activities were induced by a blood meal and the highest activities were found during the peak of trypsin activity, about 20-24h after feeding. An amino acid meal failed to induce significant increases in any of the three exopeptidase activities. The amounts of exopeptidase activities induced were proportional to the protein concentration of the meal. The addition of soy-trypsin inhibitor to the protein meal blocked the post-feeding induction of exopeptidases. The features of the induction of synthesis of the three exopeptidase activities resembled the induction of synthesis of late trypsin during the second phase of digestion.
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PMID:Midgut exopeptidase activities in Aedes aegypti are induced by blood feeding. 1277 Jan 20

The role of angiotensin converting enzyme (ACE, peptidyl dipeptidase A) in metamorphic- and reproductive-related events in the Egyptian cotton leafworm, Spodoptera littoralis (Lepidoptera, Noctuidae) was studied by using the selective ACE inhibitor captopril. Although oral administration of captopril had no effect on larval growth, topical administration to new pupae resulted in a large decrease of successful adult formation. Oviposition and overall appearance of adults emerging from treated larvae did not differ significantly from those emerging from non-treated larvae. In contrast, topical or oral administration of captopril to newly emerged adults caused a reduction in oviposition. By evaluating the effect of captopril on ecdysteroid titers and trypsin activity, we revealed an additional physiological role for ACE. Captopril exerted an inhibitory effect on ecdysteroid levels in female but not in male adults. Larvae fed a diet containing captopril exhibited increased trypsin activity. A similar captopril-induced increase in trypsin activity was observed in female adults. In male adults, however, captopril elicited reduced levels of trypsin activity. Our results suggest that captopril downregulates oviposition by two independent pathways, one through ecdysteroid biosynthesis regulation, and the other through regulation of trypsin activity. Apparently, fecundity is influenced by a complex interaction of ACE, trypsin activity, and ecdysteroid levels.
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PMID:The angiotensin converting enzyme inhibitor captopril reduces oviposition and ecdysteroid levels in Lepidoptera. 1548 60

By using the selective ACE inhibitor captopril, we studied the effect of the angiotensin converting enzyme (ACE) on larval growth, metamorphosis, and reproduction in a lepidopteran species, the cotton leafworm, Spodoptera littoralis. Captopril was detrimental to adult formation and oviposition, and in female moths it elicited decreasing ecdysteroid levels, but increasing trypsin activities. Our results suggest that captopril downregulates oviposition by two independent pathways. Apparently, oviposition is influenced by a complex interaction of ACE, trypsin activity, and ecdysteroid levels.
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PMID:ACE inhibitor captopril reduces ecdysteroids and oviposition in moths. 1589 Nov

The roles of kinin and protease-activated receptors (PAR) in endothelium-dependent relaxations to the serine protease, trypsin, were examined in rings of bovine left anterior descending coronary artery (LAD). Trypsin (0.01-30 U/ml) caused biphasic, endothelium-dependent relaxations-a high potency (0.01-0.3 U/ml), low efficacy relaxation [maximum relaxation (R (max)), 9.0 +/- 5.1%] followed by a lower potency (1-30 U/ml) but high efficacy (R (max), 90.4 +/- 5.5%) relaxation, which was abolished by aprotinin. Captopril (10 microM) caused an approximately 10-fold leftward shift of the second phase response such that the first phase was masked. The second phase relaxation to trypsin was inhibited in a concentration-dependent, non-surmountable manner by the B2 antagonist, HOE-140. At 3 nM HOE-140, the second phase response to trypsin was abolished unmasking the first phase. Kallikrein (0.0003-0.3 U/ml) caused monophasic, endothelium-dependent relaxations (R (max), 33.7 +/- 14.6%), which were potentiated by captopril (R (max), 94.2 +/- 1.0%) and abolished by HOE-140. In the presence of captopril, the second phase relaxation to trypsin was only minimally inhibited by either N(G)-nitro-L: -arginine (100 microM) or 67 mM [K(+)](o) alone but markedly reduced when these two treatments were combined (R (max), 26.1 +/- 11.6% versus 98.6 +/- 2.9% in controls). The PAR1-activating peptide, SFLLRN (0.1-30 microM), but not the PAR2-activating peptide, SLIGRL, caused concentration-dependent relaxations (pEC(50), 5.9 +/- 0.0%; R (max), 43.3 +/- 8.3%). In conclusion, trypsin causes endothelium-dependent relaxations in the bovine LAD predominantly via release of endogenous BK, which in turn activates endothelial B2 receptors. Only a minor role for PAR1-like receptors was evident in this tissue.
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PMID:B2 kinin receptor activation is the predominant mechanism by which trypsin mediates endothelium-dependent relaxation in bovine coronary arteries. 1845 78

Amaranth seed proteins have a better balance of essential amino acids than cereals and legumes. In addition, the tryptic hydrolysis of amaranth proteins generates, among other peptides, angiotensin converting enzyme (ACE) inhibitory (ACEi) peptides. ACE converts angiotensin I (Ang I) into Ang II, but is also responsible for the degradation of bradykinin (BK). In contrast to Ang II, BK stimulates vasodilation modulated through endothelial nitric oxide (NO) production. The aim of the present study was to characterize the ACEi activity of amaranth trypsin-digested glutelins (TDGs) and their ability to induce endothelial NO production. An IC(50) value of 200microgml(-1) was measured for TDG inhibition of ACE. TDGs stimulated endothelial NO production in coronary endothelial cells (CEC) by 52% compared to control. The effects of TDGs were comparable to those of BK and Captopril, both used as positive controls of NO production. Consistent with these effects, TDGs induced, in a dose-dependent manner, endothelial NO-dependent vasodilation in isolated rat aortic rings. These results suggest that TDGs induce endothelial NO production and consequent vasodilation through their ACEi activity. Amaranth TDGs have a high potential as a nutraceutical food in prevention of cardiovascular diseases. Further molecular, cellular and physiological studies are currently under way and the results may contribute to a better understanding and control of cardiovascular disorders.
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PMID:Tryptic amaranth glutelin digests induce endothelial nitric oxide production through inhibition of ACE: antihypertensive role of amaranth peptides. 2043 55


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