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)

When single-chain pro-UK is activated by plasmin or kallikrein, the Lys158-Ile159 bond is cleaved, leaving a C-terminal lysine on the A-chain (Lys-UK). Two-chain, high molecular weight urokinase (UK) purified from urine, however, has been shown to contain a phenylalanine residue as the C-terminal of the A-chain (Phe-UK). Since C-terminal lysine residues have a strong binding affinity for plasminogen that may promote its activation, we undertook kinetic studies comparing plasminogen activation by Lys- and Phe-UK. A two-stage method was employed in order to minimize factors known to interfere with plasminogen activation and plasmin determination. The Lys-UK was prepared by plasmin activation of pro-UK purified from human fetal kidney cell culture medium. The Phe-UK was prepared by carboxypeptidase B (CpB) treatment of Lys-UK. Removal of the C-terminal lysine of Lys-UK by CpB produced small but significant increases in the Michaelis constants for the activation of both Glu- and Lys-plasminogen. The apparent Michaelis constants for Glu-plasminogen activation by Lys- and Phe-UK were 3.7 microM +/- .36 microM and 5.9 microM +/- .70 microM, respectively and the Michaelis constants for Lys-plasminogen activation by Lys- and Phe-UK were 5.4 microM +/- .72 microM and 15.2 microM +/- 1.4 microM, respectively. The catalytic efficiency (kcat/Km) of Lys-UK was approximately 2-fold greater than that of Phe-UK for the activation of either Glu- or Lys-plasminogen. When the fibrinolytic activities of Lys- and Phe-UK were compared in a plasma milieu no significant differences were detected. In conclusion, the findings indicate that the C terminal lysine on the A-chain of UK significantly promotes the catalysis of plasminogen in a purified system. However, the higher catalytic efficiency of Lys-UK was not found to induce significant acceleration of clot lysis at pharmacological concentrations in plasma.
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PMID:The effect of the carboxy-terminal lysine of urokinase on the catalysis of plasminogen activation. 177 40

By activating plasminogen into plasmin, which in turn dissolves fibrin, fibrinolytic agents can dissolve pathologic thrombi. Streptokinase, a fibrinolytic agent derived from group C beta-hemolytic streptococci, is antigenic and can elicit allergic reactions. Urikinase, a fibrinolytic agent obtained by purification from human urine or from human fetal kidney cell culture, is not antigenic, and for this reason can be used repeatedly, if needed, whereas streptokinase cannot be used for retreatment within six months of a course of therapy. Either agent can be introduced into the circulation systemically (intravenously) or locally (via catheter). The indications for systemic therapy include deep-vein thrombosis, pulmonary embolism, and arterial thrombosis and embolism. The indications for local therapy include acute myocardial infarction, arterial thrombosis and embolism, and the clearing of occluded arteriovenous cannulae and access shunts. Contraindications include an actively bleeding lesion, a vascular intracranial disorder, or uncontrolled hypertension; relative contraindications include pregnancy; a recent wound, fracture, surgery, or deep closed biopsy; or a general contraindication to anticoagulation, such as coagulopathy, uremia, or severe liver disease. During thrombolytic therapy, invasive procedures, intramuscular injections, and the use of other anticoagulant or antiplatelet agents should be avoided. Measurement of fibrinogen levels, the titer of fibrin/fibrinogen degradation product, or thrombin time can be used to monitor therapy.
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PMID:Fibrinolysis and its current usage. 634 82