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)

Enzymatic properties of a protease involved in hatching of mouse embryos were examined. A trypsin-like protease, which most efficiently hydrolyzed t-butoxycarbonyl-Leu-Ser-Thr-Arg-4-methylcoumaryl-7-amide, was demonstrated in culture medium of mouse hatching embryos. The enzyme was strongly inhibited by diisopropyl fluorophosphate, phenylmethanesulfonyl fluoride, leupeptin, antipain, N alpha-tosyl-L-lysyl-chloromethane, soybean trypsin inhibitor, and Trasylol, but not or weakly inhibited by p-chloromercuribenzoic acid, EDTA, E-64, pepstatin, chymostatin, and bestatin, suggesting a trypsin-like serine proteinase. The protease activity in the medium gradually elevated during the course of hatching, whereas the embryo-associated activity showed no significant change. Furthermore, pyroglutamyl-Leu-argininal, the strongest inhibitor for the enzyme among peptidyl argininals, all of which are potent trypsin inhibitors, showed the strongest inhibition toward hatching. Thus, a trypsin-like protease secreted from hatching embryos into the culture medium may participate in mouse hatching, probably as a hatching enzyme.
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PMID:Trypsin-like hatching protease from mouse embryos: evidence for the presence in culture medium and its enzymatic properties. 218 40

Sera from patients of biliary, alcoholic, and idiopathic acute pancreatitis with severity scored from 1 to 5 based on the Ranson criteria were tested for proinsulin/insulin degrading activity. Proinsulin degrading activity by normal controls was 8 +/- 4% as compared with 22-78 +/- 17% with a mean of 45% by the patient sera. An order of magnitude increase of proinsulin degrading activity was accompanied by an order of magnitude increase of immunoreactive pancreatic cationic trypsin(ogen) and (pro)elastase-2 as determined by radioimmunoassay with day 1 sera. Proinsulin degrading activity also showed a negative correlation with the clinical time course and dropped to normal by 6 days after admission. The decrease of proinsulin degrading activity was concomitant with a decrease of serum immunoreactive pancreatic serine proteases. High-performance liquid chromatography analysis of the proteolysis products showed the appearance of insulin and smaller peptides with no proinsulin conversion intermediates. Ninety to ninety-eight percent of proinsulin degrading activity was inhibited by anti-alpha 2-macroglobulin (alpha 2-M) antiserum, or (Ac)Eglin-C(J141), and 52% by an elastase and chymotrypsin-specific inhibitor, MeOSuc-Ala-Ala-Pro-boroVal-pinacol. E64c, TLCK, alpha 1-protease inhibitor (alpha 1-PI), or Trasylol inhibited proinsulin degrading activity by 10-17%, and anti-cathepsin B antiserum by 9%. The observed proinsulin degrading activity did not correlate with the Ranson's scores, age, sex, etiology, total serum immunoreactive insulin, calcium, albumin or alpha 2-M but had a negative correlation with serum alpha 1-PI (r = -0.55) and a positive correlation with serum esterase activity (r = .62).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proteolytic degradation of human recombinant proinsulin/insulin by sera from acute pancreatitis patients and complete inhibition by Eglin-C. 240 52

The effects of human urinary trypsin inhibitor (UTI) were studied in experimental shock models. Administration of 50,000 U/kg, i.v., of UTI protected against mortality from shock induced by burn, endotoxin or trauma. Aprotinin at a dose of 50,000 U/kg improved only endotoxin shock and showed a moderate but not significant effect on burn and traumatic shock. Administration of 50,000 U/kg, i.v., of UTI protected against the aggravation in systemic hemodynamics in canine hemorrhagic shock. Furthermore, in rat traumatic shock, 50,000 U/kg, i.v., administration of UTI significantly reversed the increased serum beta-glucuronidase and trypsin activities and the decreased hepatic ATP level, and it moderately suppressed the increased serum uric acid level. Aprotinin failed to affect all these biochemical changes induced by drum trauma. These results suggest that the protective effect of UTI against experimental shock is possibly exerted through lowering the elevated enzyme activities in the serum during shock.
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PMID:Protective effects of urinary trypsin inhibitor in experimental shock. 241 41

Monitoring of plasma proteinases, proteinase inhibitors and other selective plasma proteins was evaluated in patients undergoing Y-graft aortofemoral bypass operation. Fast-reacting acute-phase proteins (C-reactive protein, antichymotrypsin, alpha 1-acid glycoprotein) and slow-reacting proteins (haptoglobin, alpha 1-antitrypsin) increased significantly 48-120 h after operation. By contrast, no significant increase was found between plasma ceruloplasmin levels before clamping and after declamping. Activity and concentration of alpha 2-macroglobulin decreased postoperatively and remained significantly lowered throughout the observation period. Plasma levels of granulocyte elastase were elevated significantly 1 h after declamping, whereas trypsin-binding capacity decreased immediately after the release of the clamp. Aprotinin pretreatment caused higher trypsin-binding capacity of the plasma, significantly lower 'unspecific' proteolytic (azocasein-hydrolyzing) activity and significantly lower non-TCA precipitable low molecular weight plasma protein concentration. Our results confirm the data of several authors that monitoring of plasma proteinases, proteinase inhibitors and other selective plasma proteins may be helpful in evaluating surgical patients postoperatively.
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PMID:Plasma proteinases, proteinase inhibitors and other selective plasma proteins following aortofemoral bypass operation. 242 35

Treatment of aprotinin with Raney nickel in the presence or absence of denaturants yielded [Ala2 14,38]aprotinin. Aprotinin and [Ala2 14,38]aprotinin were separated by ion exchange chromatography at pH 8 using CM-Sepharose, fast flow. [Ala2 14,38]aprotinin is a proteinase inhibitor, but it possesses lower affinities than aprotinin, for the enzymes trypsin, alpha-chymotrypsin, pancreatic kallikrein and plasmin as reflected by higher Ki values [Ala2 14,38]aprotinin is slowly degraded by trypsin. The optical activity of [Ala2 14,38]aprotinin in different solvents is quite similar to that of aprotinin, or that of its hydrolysis products, [seco-15/16]aprotinin or [di-seco-15/16,39/40]-aprotinin. This is taken as good evidence for analogous molecular conformations of all these substances.
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PMID:[Ala214,38]aprotinin: preparation by partial desulphurization of aprotinin by means of Raney nickel and comparison with other aprotinin derivatives. 243 18

Inhibitory effects of nafamostat mesilate (nafamostat) on various enzymes were investigated, and they were compared with those of gabexate mesilate (gabexate), leupeptin, aprotinin and urinastatin in vitro. Nafamostat inhibited trypsin, plasmin, thrombin, pancreatic kallikrein, Clr and Cls more potently than gabexate and leupeptin. Gabexate and leupeptin did not inhibit pancreatic kallikrein and thrombin, respectively. Aprotinin inhibited trypsin, plasmin, pancreatic kallikrein and chymotrypsin. Urinastatin inhibited trypsin and chymotrypsin. Nafamostat inhibited the complement-mediated hemolysis in diluted serum more potently than gabexate and leupeptin, but aprotinin and urinastatin did not. Nafamostat, furthermore, inhibited the complement-mediated hemolysis in undiluted serum, but gabexate did not. Unlike aprotinin and urinastatin, nafamostat and gabexate inhibited alpha 2-macroglobulin bound trypsin as well as free trypsin to the same extent. The inhibitory effect of gabexate toward trypsin was reduced more markedly than that of nafamostat after incubation with plasma at 37 degrees C. These results show that nafamostat is more useful than other inhibitors such as gabexate, leupeptin, aprotinin and urinastatin.
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PMID:[Comparative studies of nafamostat mesilate and various serine protease inhibitors in vitro]. 243 41

We have analyzed the effects of aprotinin and Na2CaEDTA on phospholipase A2 activity and on the outcome of experimental pancreatitis in pigs. Hemorrhagic pancreatitis was induced in 29 piglets by infusing Na-taurocholate and trypsin into the pancreatic duct with simultaneous intravenous injection of secretin. Twelve animals serving as controls had no specific treatment. Nine animals were treated with aprotinin and eight pigs with Na2CaEDTA. Ten of the control animals died within 24 h of the induction of pancreatitis, and two of them lived for a week. In the aprotinin group three piglets died within 24 h and two died during the next day; four animals lived for a week. In the Na2CaEDTA group five animals died within 24 h and one the next day; two animals lived for a week. In all the animals serum phospholipase A2 activity increased significantly (p less than 0.01), there being no differences between the groups. In those animals that lived for a week the phospholipase A2 activities decreased on the 2nd day. This decrease was seen in both treated groups. Aprotinin prolonged the survival time of the animals. This prolongation was statistically significant (p less than 0.05, chi-square test, logrank test). Na2CaEDTA did not improve the prognosis of the animals. Neither of the drugs given influenced the serum phospholipase A2 activities during the first hours of the disease.
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PMID:Aprotinin and Na2CaEDTA in experimental hemorrhagic pancreatitis in pigs. 243 80

Activity of peritoneal plasminogen activator and its regulation by dextran and other macromolecules that clinically suppress postoperative adhesions was studied. Plasminogen activator activity was assayed by a two-stage globinolytic assay that monitors formation of plasmin, as well as by cleavage of a chromogenic peptide substrate (S-2444) in the presence of aprotinin (Trasylol). Plasminogen activator activity was located on the outer surface of human peritoneum. Incubation of peritoneal tissue with buffer in vitro (conditioning) prompted release of plasminogen activator into the conditioning medium. The released plasminogen activator formed a single band on sodium dodecyl sulfate-gel electrophoresis at an apparent molecular weight of 174,000 and was markedly suppressed by antiserum raised against human melanoma tissue-type plasminogen activator. Nonspecific proteolytic activity did not accumulate in the medium during conditioning. The presence of dextran 80 during conditioning of peritoneum reversibly suppressed tissue-bound plasminogen activator activity and reduced plasminogen activator activity in the spent medium. A similar inhibition of peritoneal plasminogen activator was induced by dextran 500, methyl cellulose, and polyvinylpyrrolidone. Dextran, when added to the medium after conditioning, had no direct inhibitory effect on plasminogen activator activity. Dextran did not induce peritoneal production of inhibitor(s) of trypsin, chymotrypsin, or urokinase. On the basis of these findings, two possible mechanisms for the effect of viscous polymers in the reduction of adhesion formation are proposed. These mechanisms consider the importance of peritoneal tissue-type plasminogen activator for removal of fibrin clots and suggest that polymer coating either prevents the shedding of plasminogen activator into the abdominal cavity or reduces the access of fibrin clots to the serosal surfaces.
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PMID:Effect of viscous macromolecules on peritoneal plasminogen activator activity: a potential mechanism for their ability to reduce postoperative adhesion formation. 245 68

Aprotinin, a polypeptide inhibitor of trypsin-like enzymes, has been labelled with rhodamine. Rhodamine-aprotinin inhibits trypsin in free solution in an identical manner to aprotinin. Rhodamine-aprotinin binds to trypsin-like enzymes on cells in formaldehyde fixed wax embedded sections. This technique has been used to locate cells possessing trypsin-like enzymes by means of fluorescent microscopy. In the present study we have used this technique to locate tumour cells.
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PMID:Inhibition of trypsin-like enzymes on cells with rhodamine-aprotinin. 247 Aug 78

Aprotinin derivatives with decarboxylated lysine, arginine or valine at position 15, the P1 position of modified aprotinin, were produced semisynthetically. Modified aprotinin with oxidatively deaminated Arg1 and Ala16 was also synthesized. Specific reduction of this derivative yielded a modified aprotinin with lactic acid at position 16, the P'1 position. Only the aprotinin derivatives with decarboxylated Lys15 or Arg15 showed moderate inhibitory activity against trypsin and kallikrein, despite the absence of the carboxyl group. The KD values measured were in the range of 10(-7) M. The aprotinin derivative with decarboxylated valine showed no inhibitory activity; neither against trypsin, kallikrein and chymotrypsin, nor against the human leukocyte elastase. From these data it was concluded that the ion-pair interaction of the Lys15, or the Arg15 inhibitor side-chain with the aspartate in the trypsin specificity pocket is important for the inhibitory activity. Furthermore, the KD values indicated that the interaction of the reactive-site's carbonyl group with the enzyme's oxyanion hole also contributes to the inhibitory activity. These two interactions are important, but not essential for inhibitory activity. In contrast to these findings, the existence of an alpha-amino group at the P'1 position seems to be essential for inhibitory activity. The synthesized aprotinin derivatives lacking an alpha-amino group at this position were without any inhibitory activity against serine proteinases.
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PMID:Semisynthetic aprotinin derivatives with specific alterations at the reactive-site peptide bond can be used to study structure-function relationships. 247 74


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