Course and prerequisites of Lys-plasminogen formation during fibrinolysis

Journal Article · Tue Apr 05 04:00:00 EDT 1988 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00407a029· OSTI ID:5176159

Suenson, E; Thorsen, S

Plasmin-catalyzed modification of the native plasma zymogen Glu/sub 1/-plasminogen to its more reactive LYS/sub 7//sup 8/ form has been shown to be enhanced in the presence of fibrin. The aim of the present work has been to characterize the influence of fibrinopeptide release, fibrin polymerization, and plasmin cleavage of fibrin on the rate of Lys/sub 78/-plasminogen formation. /sup 125/I-Labeled Glu/sub 1/- to Lys/sub 78/-plasminogen conversion was catalyzed by preformed Lys/sub 78/-plasmin, or by plasmin generated during plasminogen activation with tissue plasminogen activator or urokinase. The two forms of plasminogen were quantitated following separation by polyacrylamide gel electrophoresis in acetic acid/urea. Plasmin generated by plasminogen activator was monitored by a fixed-time amidolytic assay. The rate of Lys/sub 78/-plasminogen formation was correlated, in separate experiments, to the simultaneous, plasmin-catalyzed cleavage of /sup 125/I-labeled fibrinogen or fibrin to fragments X, Y, and D. The radiolabeled components were quantitated after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results show that the formation of both bathroxobin-catalyzed des-A-fibrin and thrombin-catalyzed des-AB-fibrin leads to marked stimulation of Lys/sub 78/-plasminogen formation, whereas inhibition of fibrin polymerization, with Gly-Pro-Arg-Pro, abolishes the stimulatory effect. The rate of Lys/sub 78/-plasminogen formation varies markedly in the course of fibrinolysis. It is concluded that efficient conversion of Glu/sub 1/ to Lys/sub 78/-plasminogen requires formation of des-A or des-AB fragment X polymer, in the absence of significant quantities of fragments Y and D. Under these conditions, Lys/sub 78/-plasminogen formation is a potent stimulatory mechanism in fibrinolysis.

• Research Organization: Univ. of Copenhagen (Denmark)
• OSTI ID: 5176159
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:7; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
AMINO ACIDS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOCHEMISTRY
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CHEMISTRY
COAGULANTS
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ELECTROPHORESIS
FIBRIN
FIBRINOLYSIS
FIBRINOLYTIC AGENTS
GLUTAMIC ACID
HALIDES
HALOGEN COMPOUNDS
HEMATOLOGIC AGENTS
HEMOSTATICS
INORGANIC PHOSPHORS
INTERMEDIATE MASS NUCLEI
IODIDES
IODINE 125
IODINE COMPOUNDS
IODINE ISOTOPES
ISOTOPES
KINETICS
LABELLING
LYSINE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHOSPHORS
PLASMINOGEN
PROTEINS
PROTEOLYSIS
RADIOISOTOPES
REACTION KINETICS
SCLEROPROTEINS
SODIUM COMPOUNDS
SODIUM IODIDES