Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When human plasminogen (Glu-Pga) is activated by urokinase in the presence of pancreatic trypsin inhibitor, the plasmin produced (Glu-Pma) exclusively contains a heavy chain (Glu-Ha) derived intact from the original NH2 terminus of Glu-Pga. Similar activations, utilizing a low molecular weight synthetic plasmin acylating agent, p-nitrophenyl-p-(pyridiniummethyl) benzoate, still result in a plasmin molecule with approximately 50% of the plasmin heavy chain containing the intact NH2 terminus of the original Glu-Pga. Activations performed at high levels of urokinase in the absence of any inhibitors initially produce Glu-Pma. However, the final stable plasmin, Lys-Pmb, which is obtained contains a heavy chain (Lys-Hb) which arises by plasminolysis of a small peptide from the NH2 terminus of Glu-Ha. Alternatively, Lys-Pmb can be formed in a separate series of reactions initially involving plasminolysis of Glu-Pga to yield Lys-Pgb. The peptide removed in this step is identical to the peptide removed in the Glu-Ha to Lys-Hb reaction. Next, urokinase catalyzes the conversion of Lys-Pgb to Lys-Pmb without further loss of peptide material. This latter pathway involving Lys-Pgb is probably the major pathway for human Lys-Pmb generation. These studies support a mechanism of activation of human plasminogen which involves at least two bond cleavages in Glu-Pga. However, these same studies strongly indicate that the Nh2-terminal peptide need not be released from Glu-Pga prior to plasmin formation. Further, we feel that plasmin and not urokinase catalyzes cleavage of the NH2-terminal peptide bond from Glu-Pga and the Glu-Ha heavy chain of Glu-Pma.
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PMID:Mechanism of the urokinase-catalyzed activation of human plasminogen. 13 42

Folinic acid-modulated 5-FU regimens are standard elements in several chemotherapy combinations like FOLFIRI, FOLFOX or AIO-regimen in the palliative treatment of patients with gastrointestinal cancer. When the simultaneous mixed infusion of 5-FU and calcium-folinic acid (Leucovorin) was authorized by the BfArM in 2002, we introduced this application regimen in the treatment of our cancer patients. 19 patients (AIO-regimen [5], FOLFIRI [12] and FOLFOX [2]) received a simultaneously mixed infusion of calcium-folinic acid and 5-FU over 24 hours with a total of 110 applications. 5-FU doses varied between 2000 and 2600 mg/m2, calcium-folinic acid was given with 500 mg/m2, infusion rate was 10 ml/hour using a 24 h pump. Central venous catheters employed included single Barth-Port in 18 cases, 1 patient had a Viggon-Port. In 3 out of the 19 patients catheter occlusion was noticed after 8-10 weekly applications of the mixed infusion. Heparine and subsequently urokinase were not successful in reversing the obstruction. All three catheters had to be explanted. Catheter tips in all cases showed a yellow cristalline precipitation. The crystallographic analysis exhibited calcium carbonate (CaCO3) in its polymorphic form (calcite). Thus, we confirmed calcite formation causing catheter occlusion as a frequent complication during a continuous 24 h-infusion of mixed high dose 5-FU and calcium-folinic acid. This reaction could not be avoided by increasing infusion volume and the application flow rate. As a result of our findings, recommending using calcium-folinic acid mixed with 5-FU has been withdrawn in the meantime.
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PMID:[Occlusion of central venous port catheters after simultaneous 24 h infusions of 5-FU and calcium-folinic acid in patients with gastrointestinal cancer]. 1524 42