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:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastric juice from 15 normals, 20 patients with gastric ulcer and 14 patients with erosive haemorrhagic gastroduodenitis was investigated in respect of its activity on unheated and heated fibrin plates and its content of FDP and plasminogen or plasmin with immunochemical methods. Gastric juice from normals showed no activity on unheated and heated fibrin plates, and no FDP or plasminogen could be demonstrated. In the patients with gastric ulcer the gastric juice showed little or no fibrinolytic activity on fibrin plates except in 2, who had regurgitation of duodenal juice and neutral pH of the juice. These patients had equally high activity on heated as on unheated plates and no plasmin could be demonstrated. It was shown that this activity was not due to fibrinolysis, but to non-specific proteolytic activity (probably trypsin). The patients with erosive haemorrhage gastroduodenitis exhibited quite a different picture. The gastric juice from these patients showed extremely high activity on fibrin plates, the activity was higher on unheated than on heated plates. The activity was inhibited in vitro by addition of EACA and in vivo after administration of AMCA. The occurence of plasmic could be demonstrated directly immunologically in the gastric juice. By comparsion of plasmin and trypsin in various assays it could further be improved that the gastric juice in these cases contained plasminogen activator and plasmin. The patients with erosive haemorrhagic gastroduodenitis showed no increase in fibrinolysis in the blood, but low values for plasminogen and alpha2-M, and the serum contained FDP. These findings in the blood and gastric juice were interpreted as signs of local fibrinolysis in the stomach and duodenum. There is reason to assume that this gastric fibrinolysis contributes substantially to the bleeding tendency. The effect of administration of AMCA on fibrinolytic activity and the haemorrhage lends support to the assumption of such a mechanism.
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PMID:Gastric fibrinolysis. 0 Aug 7

The major plasmin inhibitors namely alpha2-plasmin inhibitor and alpha2-macroglobulin were compared for their effects on lysis of fibrin clot. Plasmin fibrinolytic activity was immediately inhibited by alpha2-plasmin inhibitor, whereas alpha2-macroglobulin inhibited plasmin progressively. Urokinase(plasminogen activator)-induced clot lysis was inhibited efficiently by alpha2-plasmin inhibitor present in the clot. Inhibition of urokinase-induced clot lysis by alpha2-macroglobulin was weak and the molar concentration necessary for alpha2-macroglobulin to achieve the same degree of inhibition as that achieved with alpha2-plasmin inhibitor was about 10 times higher than that of alpha2-plasmin inhibitor. Binding of Lys-plasminogen to fibrin was inhibited by alpha2-plasmin inhibitor but not by alpha2-macroglobulin. Molar concentrations of alpha2-plasmin inhibitor which were effective in inhibiting the binding were 30 times less than that of 6-aminohexanoicacid. alpha2-Plasmin inhibitor was found to interact with Lys-plasminogen to form a weakly-bound complex which is dissociable in the presence of 6-aminohexanoic acid, suggesting that inhibition of binding of Lys-plasminogen to fibrin by alpha2-plasmin inhibitor may be due to interaction of alpha2-plasmin inhibitor with a specific site of the plasminogen molecule and that the site may be 6-aminohexanoic acid-binding site. It is suggested that alpha2-plasmin inhibitor is more reactive and efficient inhibitor of fibrinolysis than alpha 2-macroglobulin.
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PMID:Effects of alpha2-plasmin inhibitor on fibrin clot lysis. Its comparison with alpha2-macroglobulin. 7 50

Pretreatment of native plasminogen with plasmin or activators resulted in a pronounced increase in the binding of plasminogen to fibrin. The pretreated plasminogen was considered to be identical to the proteolytically degraded proenzyme with NH2-terminal lysine, valine or methionine, which is formed as an intermediate stage during activation of plasminogen. Bound plasminogen could be extracted by 6-aminohexanoic acid indicating a reversible binding between plasminogen and fibrin. Adsorption of pretreated plasminogen decreased when increasing concentrations of 6-aminohexanoic acid or trans-4-aminomethylcyclohexane-1-carboxylic acid (t-AMCHA) were present during fibrin formation. The concentration of amino acid producing a decrease in the binding of pretreated plasminogen to 0.5 of the amount bound in the absence of amino acid was 8.0-10(-5) M with 6-aminohexanoic acid and 1.7.10-5 M with t-AMCHA. The decrease in binding is most likely related to an effect of the amino acids on plasminogen, since agarose gel electrophoresis of pretreated plasminogen in the presence of 6-aminohexanoic acid or t-AMCHA showed a cathodic shift in mobility at the same range of concentrations of amino acid, which produced the decrease in binding of plasminogen to fibrin. Evidence is provided that the decrease in binding of proteolytically degraded plasminogen may result in an inhibition of fibrinolysis caused by activators.
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PMID:Differences in the binding to fibrin of native plasminogen and plasminogen modified by proteolytic degradation. Influence of omega-aminocarboxylic acids. 12 94

A method is described by which the heavy chain of human plasmin, obtained by partial reduction of urokinase-activated plasminogen with 2-mercaptoethanol, is adsorbed on lysine coupled to polyacrylamide. The heavy chain is recovered from the adsorbent by elution with 6-aminohexanoic acid (yield 60-65%). Sulfhydryl titrations of the heavy chain showed that the partial reduction involved primarily the cleavage of the sole interchain disulfide bridge of plasmin. Dodecylsulfate-polyacrylamide electrophoresis gave essentially a single band corresponding to a component of about 60000 molecular weight. The NH2-terminal amino acid was predominantly threonine. 6-Aminohexanoic acid at different concentrations caused significant variations of the sedimentation and diffusion constants of the heavy chain indicating inhibitor-induced conformational alterations of the protein. The present results suggest that in plasmin only the heavy chain is capable of interacting with 6-aminohexanoic acid, and it appears that it is primarily this chain which plays an important role in the inhibition of the enzyme by 6-aminohexanoic acid.
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PMID:A new method of isolation and some properties of the heavy chain of human plasmin. 12 54

Previous studies of the natural history of embolized clots in dogs have demonstrated rapid lysis, presumably because the canine fibrinolytic system is very active. The fibrinolytic activity in swine, however, is similar to humans, and for this reason the pig was chosen for our study. The gluteal branches of the external iliac artery in nine domestic swine were embolized with either unmodified or modified (heat-formed, Amicar) autologous clot. In addition, three pigs were embolized with unmodified autologous clot to branches of the gastrosplenic artery. The lysis of clot emboli in both groups was followed by serial angiography at 48 hours and 14 days. Clot lysis as assessed by euglobulin lysis and plasmin generation was not activated by the experimental technique. Necropsy was performed on the animals in the second group. Partial or total obstruction of all arteries was present 48 hours after embolization and only 50% of arteries were recanalized at 14 days. At necropsy, organized partially occluding clot was demonstrated in the splenic artery of all 3 embolized swine. It is concluded that: 1)swine provide an excellent animal model for studying the natural history of arterial embolization; 2)Amicar or heat-formed clot shows no advantage over simple autologous clot in retarding intra-arterial clot lysis, and 3)simple autologous clot is an effective material for temporary intra-arterial occlusion.
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PMID:Natural history of autologous blood clot embolization in swine. 13 2

Fibrinogen was depleted in dogs injected with a single dose of bothropase even if pretreatment followed by a continuous infusion of antifibrinolytic drugs was performed during defibrination. The activation of the fibrinolytic system as a secondary effect of the defibrination syndrome induced by bothropase injection was blocked completely by aprotinin (Trasylol) but not by EACA. Plasmin activity in spite of the inhibition of plasminogen activator suggests that, either an excess of activator is released in circulation or a plasmin-antiplasmin complex is dissociated by the circulating fibrin, according to the hypothesis of Ambrus and Markus [1], and Back et al. [4] for the mechanism of fibrinolysis in vivo. An experimental model is suggested for the study of the fibrinolytic mechanism in vivo, by the association of defibrinating agents, antivenom and antifibrinolytic drugs.
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PMID:Experimental defibrination and bothropase: a study on the fibrinolytic mechanism in vivo. 14 12

The reaction between antiplasmin (A) and a low-molecular-weight form of plasmin (P) proceeds in at least two steps: a fast reversible second-order reaction followed by a slower irreversible first-order transition, and may be represented by: P +A k1 in equilibrium k-1 PA k2 leads to PA'. The low-Mr plasmin, which is obtained by limited elastase digestion, is composed of an intact B chain and a small A chain lacking the lysine-binding sites. The k1 of the reaction is (6.5 +/- 0.5) x 10(5) M-1 s-1 which is 30--60 times smaller than that for normal plasmin and antiplasmin. The dissociation constant of the first step is 1.9 x 10(-9) M which is 10 times higher than for normal plasmin and antiplasmin. The rate constant of the second step is (4.2 +/- 0.2) x 10(-3) s-1 for both normal and low-Mr plasmin. Low Mr plasmin which has substrate bound to its active site does not react or reacts only very slowly with antiplasmin. The reaction rate, however, is only slightly influenced by 6-aminohexanoic acid in concentrations up to 1 mM which decrease the reaction rate of normal plasmin approximately 50-fold. The findings further indicate that the lysine-binding site(s) of plasmin are of great importance for the rate of its reaction with antiplasmin.
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PMID:On the kinetics of the reaction between human antiplasmin and a low-molecular-weight form of plasmin. 14 57

The effects of L-lysine, 6-aminohexanoic acid, and trans-4-aminomethylcy-clohexane-1-carboxylic acid on the catalytic activity of plasmin (EC 3.4.21.7) have been investigated. The kinetics of the plasmin-catlysed hydrolysis of alpha-N-benzoyl-L-arginine ethyl ester in the presence of these compounds have been studied at a number of different concentrations of the three modifiers. They each exert two effects on the reaction, an activation and an inhibition, the concentration dependencies of which are markedly different. They must therefore arise from two different interactions between plasmin and the modifier. The inhibition is competitive, so that it most probably results from direct interaction at the catalytic site. The activation is kinetically non-competitive. The experimental observations seem to be explained best by assuming that L-lysine and certain analogous compounds function as both allosteric modifiers and competitive inhibitors of plasmin.
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PMID:Allosteric effects of some antifibrinolytic amino acids on the catalytic activity of human plasmin. 15 Aug 62

The primary inhibitor of plasmin in human plasma was purified by a four-step procedure involving fractional (NH(4))(2)SO(4) precipitation, ion-exchange chromatography on a column of DEAE-Sepharose CL-6B and affinity chromatography on both a plasminogen-CH-Sepharose 4B column and a column of 6-aminohexanoic acid covalently coupled through the carboxylate function to AH-Sepharose 4B. No impurities in the final preparation could be detected when tested by immunoelectrophoresis against a range of specific antisera or against rabbit anti-human serum. On polyacrylamide-gel electrophoresis the inhibitor preparation showed a single band. The dissociation constant for the inhibitor-plasminogen complex was determined to be approx. 3mum at pH7.8. The reactions of the inhibitor with human plasmin and with bovine trypsin were studied. Comparison of the results obtained confirms the hypothesis previously presented, namely that the reaction of the inhibitor with plasmin involves at least two steps, the initial rapid formation of an enzyme-inhibitor complex followed by a slow irreversible transition to another complex. The results also indicate that the reaction of the inhibitor with trypsin involves just a single, irreversible step, so that this reaction seems to be less complicated than that of the inhibitor with plasmin. The ways in which 6-aminohexanoic acid influences the reactions were studied. The same value for the dissociation constant (approx. 26mum) for 6-aminohexanoic acid is obtained for both its effect on the reaction of the inhibitor with trypsin and for competitive inhibition of trypsin. The inhibitory effect of 6-aminohexanoic acid thus seems to be due to its blocking of the active site of trypsin. In contrast with this, the inhibitory effects of l-lysine and 6-aminohexanoic acid on the inhibitor-plasmin reaction occur at concentrations much too low to affect the active site of plasmin. The possible dependence of the reaction of the inhibitor with plasmin on a second site(s) on plasmin is discussed.
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PMID:Purification and reaction mechanisms of the primary inhibitor of plasmin from human plasma. 15 22

Plasminogen and plasminogen derivatives which contain lysine-binding sites were found to decrease the reaction rate between plasmin and alpha2-antiplasmin by competing with plasmin for the complementary site(s) in alpha2-antiplasmin. The dissocwation constant Kd for the interaction between intact plasminogen (Glu-plasminogen) and alpha2-antiplasmin is 4.0 microM but those for Lys-plasminogen or TLCK-plasmin are about 10-fold lower indicating a stronger interaction. The lysine-binding site(s) which is situated in triple-loops 1--3 in the plasmin A-chain is mainly responsible for the interaction with alpha2-antiplasmin. The interaction between Glu-plasminogen and alpha2-antiplasmin furthermore enhances the activation of Glu-plasminogen by urokinase to a comparable extent as 6-aminohexanoic acid, suggesting that similar conformational changes occur in the proenzyme after complex formation. Fibrinogen, fibrinogen digested with plasmin, purified fragment E and purified fragment D interfere with the reaction between plasmin and alpha2-antiplasmin by competing with alpha2-antiplasmin for the lysine-binding site(s) in the plasmin A-chain. The Kd obtained for these interactions varied between 0.2 microM and 1.4 microM; fragment E being the most effective. Thus the fibrinogen molecule contains several complementary sites to the lysine-binding sites located both in its NH2-terminal and COOH-terminal regions; these sites are to a large extent.
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PMID:On the specific interaction between the lysine-binding sites in plasmin and complementary sites in alpha2-antiplasmin and in fibrinogen. 15 66


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