Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Further evidence is presented that the acrosomal proteinase acrosin exists as a zymogen precursor in freshly ejaculated boar spermatozoa. Autoactivation of proacrosin to acrosin takes place optimally at slightly alkaline pH and in the presence of calcium ions. Activation is considerably accelerated by catalytic amounts of trypsin or highly purified acrosin. A significant acceleration of the activation is also achieved by porcine pancreatic and urinary kallikrein, whereas chymotrypsin, plasmin, thrombin or urokinase showed no effect. Activation can be inhibited by p-amino-benzamidine and p-nitrophenyl p'-guanidino-benzoate. Electrophoretic analysis at different stages of activation revealed that during this process various molecular forms of acrosin are produced, apparently by limited proteolysis.
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PMID:Multiple forms of boar acrosin and their relationship to proenzyme activation. 0 66

A kallikrein inhibitor was found in tubules of the rat kidney and purified by chromatography on Sephadex G-100. The molecular weight of the inhibitor, estimated by gel filtration and dodecylsulfate electrophoresis, is about 4700. It inhibits the following kallikreins: porcine submanidbular and pancreatic kallikrein, rat kidney and urine kallikrein, and human urine and plasma kallikrein. An inhibition of bovine trypsin was not observed.
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PMID:A kallikrein-specific inhibitor in rat kidney tubules. 0 50

The kallikrein inhibitor contents of human and animal plasma were determined with glandular kallikreins [EC 3.4.21.8]. One ml of plasma could inactivate 20-700 kallikrein units (KU). Rat plasma was the most potent and inactivated 230-700 KU. However, no enzyme capable of inactivating kallikrein could be found in this plasma. Two fractions which inhibited hog pancreatic kallikrein, a fraction corresponding to alpha2-macroglobulin and a fraction which was eluted prior to albumin, were separated from rat plasma by Sephadex G-200 gel filtration. The former inhibitor could inhibit hog pancreatic kallikrein action on Nalpha-benzoyl-L-arginine ethyl ester (BAEE) as well as in the dog vasodilator assay. The other inhibitor was partially purified from rat plasma. One mg of the preparation inhibited 67 KU and the hydrolysis of 5.8 micronmoles/min of BAEE by hog pancreatic kallikrein [EC 3.4.21.8]. The inhibitor also inhibited other glandular and plasma kallikreins, trypsin [EC 3.4.21.4], alpha-chymotrypsin [EC 3.4.21.1], etc. The optimal pH of the inhibitor was 7.5-8. The inhibitor was unstable below pH 5, and was destroyed by heating at temperature above 60 degrees. The isoelectric point of the inhibitor was determined by Ampholine focusing to be 4.4, and its molecular weight was estimated to be 73,000 by Sephadex G-100 and G-150 filtrations. Several experimental results suggested that this inhibitor differed from alpha1-antitrypsin.
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PMID:Kallikrein inhibitors in rat plasma. 1 35

Pancreatic and urinary kallikreins failed to form the typical serine proteinase complex with alpha2M (alpha2-macroglobulin). Studies were performed to compare this with the binding of trypsin to alpha2M at various molar binding ratios, with the use of Sephadex G-200 gel filtration to separate free and alpha2M-bound enzyme fractions. The subunit conversion was totally absent with pancreatic kallikrein from lhich traces of a binding proteinase had been removed. The lack of binding is believed to be the result of the restricted specificity of the kallikreins.
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PMID:Absence of binding of pancreatic and urinary kallikreins to alpha 2-macroglobulin. 6 Oct 28

The acid-labile inter-alpha-trypsin inhibitor is cleaved enzymatically in vivo, liberating a smaller acid-stable inhibitor. The molar ratio of native inhibitor to this smaller inhibitor in plasma is significantly changed in some severe cases of inflammation and kidney injury. To clarify this observation on a molecular basis, the action of four different types of proteinases (trypsin, plasmin, kallikrein and granulocyte elastase) on the inter-alpha-trypsin inhibitor was studied. The initial rate of cleavage of the inter-alpha-trypsin inhibitor by a 1.3-fold molar excess of proteinase over inhibitor was found to be 4375 nM x min-1 with granulocyte elastase, 860 nM x min-1 with trypsin, 67 nM x min-1 with plasmin, and 0.3 nM X min-1 with kallikrein. Obviously, of the enzymes studied so far, the granulocyte elastase known to be released during severe inflammatory processes is by far the most potent proteinase in the transformation of the inter-alpha-trypsin inhibitor. The inter-alpha-trypsin inhibitor and its cleavage products inhibit bovine trypsin very strongly (Ki = 10(-9)--10(-11) M), porcine plasmin much less strongly, human plasmin very weakly and pancreatic kallikrein practically not at all.
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PMID:Human inter-alpha-trypsin inhibitor. Limited proteolysis by trypsin, plasmin, kallikrein and granulocytic elastase and inhibitory properties of the cleavage products. 9 50

A prekallikrein has been demonstrated in human pancreatic juice and the active enzyme has been purified from this material. The purification procedure included filtration on Sephadex G-100, chromatography on DEAE-cellulose and affinity chromatography on trypsin-inhibitor Sepharose. The purified kallikrein appeared to be homogeneous by polyacrylamide gel electrophoresis at pH 8.3 and by immunoelectrophoresis. Human pancreatic kallikrein is immunologically different from human plasma kallikrein and from pancreatic kallikreins of other species (hog, cat, rat and dog). Human pancreatic kallikrein has common antigenic determinants with human urinary and submandibular kallikreins but probably not with parotid kallikrein.
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PMID:Characterization and purification of a kallikrein from human pancreatic juice and immunological comparison with other kallikreins. 10 89

The reactive-site sequence of a proteinase inhibitor can be written as . . . -P3-P2-P1-P'1-P'2-P'3- . . . , where-P1-P'1-denotes the reactive site. Three semisynthetic homologues have been synthesized of the bovine trypsin-kallikrein inhibitor (Kunitz) with either arginine, phenylalanine or tryptophan in place of the reactive-site residue P1, lysine-15. These homologues correspond to gene products after mutation of the lysine 15 DNA codon to an arginine, phenylalanine or tryptophan DNA codon. Starting from native (virgin) inhibitor, reactive-site hydrolyzed, still active (modified) inhibitor was prepared by chemical and enzymic reactions. Modified inhibitor was then converted into inactive des-Lys15-inhibitor by reaction with carboxypeptidase B. Inactive des-Lys15-inhibitor was reactivated by enzymic replacement of the P1 residue according to Leary and Laskowski, Jr. The introduction of arginine was catalyzed by an inverse reaction with carboxypeptidase B, while phenylalanine or tryptophan were replaced by carboxypeptidase A. The reactivated semisynthetic inhibitors were trapped by complex formation with either trypsin or chymotrypsin. The enzyme - inhibitor complexes were subjected to kinetic-control dissociation, and the semisynthetic virgin inhibitors were isolated. The inhibitory properties of the semisynthetic inhibitors have been investigated against bovine trypsin and chymotrypsin and against porcine pancreatic kallikrein and plasmin. The homologues with either lysine or arginine in the P1 position are equally good inhibitors of trypsin, plasmin and kallikrein. The Arg-15-homologue is a slightly more effective kallikrein inhibitor than the Lys15-inhibitor. The semisynthetic phenylalanine and tryptophan homologues, however, are weak inhibitors of trypsin and still weaker inhibitors of kallikrein, but are excellent inhibitors of chymotrypsin. Their association constant with chymotrypsin is at least ten times higher than that of native Lys-15-inhibitor. A dramatic specificity change is observed with the phenylalanine and tryptophan homologues, which in contrast to the native inhibitor do not at all inhibit porcine plasmin. Thus, the nature of the P1 residue strongly influences the primary inhibitory specificity of the bovine inhibitor (Kunitz).
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PMID:Replacement of lysine by arginine, phenylalanine and tryptophan in the reactive site of the bovine trypsin-kallikrein inhibitor (Kunitz) and change of the inhibitory properties. 12 27

Two acid stable proteinase inhibitors are present in bull seminal plasma and washed ejaculated bull spermatozoa. Inhibitor I with a molecular weight of about 8700 (estimated by gel filtration) is a very strong inhibitor of bull sperm acrosin but also inhibits bovine trypsin and chymotrypsin and porcine plasmin; inhibition of porcine pancreatic and urinary kallikrein was not observed. In this respect inhibitor I resembles the well known cow colostrum trypsin inhibitor. Inhibitor II with a molecular weight near 6800 (estimated by gel filtration) inhibits bovine trypsin and chymotrypsin, porcine plasmin and pancreatic and urinary kallikrein as well as bull acrosin. The inhibition specificity of inhibitor II is thus very similar to that of the basic inhibitor from bovine organs (Kunitz-type). In view of the inhibition strength and other characteristics, however, the acid stable bull seminal inhibitors are not identical with the inhibitor from cow colostrum or bovine lung (organs).
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PMID:Characterization of the proteinase inhibitors from bull seminal plasma and spermatozoa. 13 81

The excretion of kallikrein in urine varies, but the pathophysiologic implications are not clear. To help clarify the role of the urinary kallikrein-kinin system, we have begun to define components of the system as they occur in urine. To minimize artifacts which may arise through extensive purification procedures, we studied urinary protein concentrates prepared by ultrafiltration. The concentrates were separated by chromatography on Sephacryl. Urine contains abundant kininase activity, but in strongly inhibited forms. Kininase II is separable into at least two forms. Another major kininase can hydrolyze benzoyl-Pro-Phe-Arg and is inhibited by arginine but not by BPP9a or SQ 14,225. Its molecular weight is approximately 63,000. A third kininase, not inhibited by BPP9a, is excluded from Sephacryl. Human urine appears to contain only one kallikrein-like enzyme (MW 45,000). In addition, urine contains a protein (MW approximately 80,000) which reacts with trypsin to release bradykinin and which inhibits the hydrolysis of Pro-Phe-Arg-[3H]anilide by urinary kallikrein. Thus, in addition to kallikrein and kinins, urine contains kininogen and at least three kininase enzymes. Urinary ultrafiltrate contains an inhibitory substance (approximately MW 400).
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PMID:Components of the kallikrein-kinin system in urine. 22 42

A human colon kininogenase (kallikrein) was isolated by gel filtration on Sephacryl S-200 and affinity chromatography on Trasylolbound Sepharose, yielding a material with a specific activity of 1.3 U/mg (substrate: AcPheArgOEt). The molecular weight of the enzyme as estimated by gel filtration is approximately 70 000. After reduction with mercaptoethanol two bands were obtained in dodecyl sulfate eletrophoresis with molecular weights of 27 000 and 70 000. The bimolecular velocity constant for the inhibition by diisopropyl fluorophosphate was determined as 4 l x mol-1 x min-1. The preparation was characterized by immunological and enzymatic methods. Using the radioimmumoassay for human urinary kallikrein cross-reactivity and parallel binding curves were obtained. Kinin liberation from human high Mr-kininogen was totally inhibited by antibodies directed against human urinary kallikrein. Trasylol and diisopropyl fluorophosphate, but not by antibodies directed against human trypsin and plasma kallikrein. The effect on dog blood pressure was comparable to that obtained with human urinary kallikrein. The amino acid composition of human large intestine kallikrein is very similar to that of human urinary kallikrein.
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PMID:Similarity between a kininogenase (kallikrein) from human large intestine and human urinary kallikrein. 26 Sep 27


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