Kinetic study on the initial stage of the fibrinogen-fibrin conversion by thrombin. (IV). Effects of heparin and its analogues.
From kinetic analysis on the initial stage of the fibrinogen-fibrin conversion catalyzed by thrombin, inhibition constants, Kip, of heparin and heparin analogues were obtained by the turbidimetrical method. The inhibitory effect per unit amount in weight of heparin and heparin analogues increased generally with decreasing concentration, and their modes of inhibition changed. In the fibrinogen and thrombin system, heparin and its analogues were observed to act as noncompetitive inhibitors at high concentrations, where the inhibition constant of heparin was 3.91 X 10(-6) M. At low concentrations below 10(-5) M, both heparin and dextran sulphate acted as hyperbolic competitive inhibitors of thrombin, and Kip of heparin was 1.07 X 10(-8) M, which was measured at heparin concentrations below ca. 10(-8) M. It was presumed that heparin has electrostatic interaction with the active site of thrombin or the binding site located near the active site of thrombin.
D000818:Animals; D002417:Cattle; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006493:Heparin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007700:Kinetics; D008433:Mathematics; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000378:metabolism*
D005337:Fibrin; D005340:Fibrinogen; D006493:Heparin; D013917:Thrombin