The effect of 6-aminohexanoic acid and fucoidan on the activation of glutamic plasminogen by streptokinase

• Published in: Blood coagulation & fibrinolysis Vol. 13; no. 4; p. 355
• Main Authors: Harris, G, Doctor, V M
• Format: Journal Article
• Language: English
• Published: England 01.06.2002
• Subjects: Aminocaproic Acid - pharmacology; Anticoagulants - pharmacology; Dose-Response Relationship, Drug; Humans; Kinetics; Plasminogen - chemistry; Plasminogen - drug effects; Plasminogen - metabolism; Polysaccharides - pharmacology; Protein Binding; Protein Conformation - drug effects; Sodium Chloride - pharmacology; Streptokinase - drug effects; Streptokinase - metabolism
• ISSN: 0957-5235
• DOI: 10.1097/00001721-200206000-00012

Studies were conducted on the effect of 6-aminohexanoic acid (6-AH) or fucoidan on the activation of glutamic plasminogen (glu-plg) by streptokinase using 0.05 mol/l Tris buffer containing a physiological concentration of NaCl. In contrast to the earlier reports where no NaCl was added to the buffer solution, addition of 6-AH enhanced the initial rate while the inhibition by fucoidan was not affected. Double reciprocal plots of the activation of glu-plg by streptokinase in the presence of 6-AH showed an increase in Vmax, but no change in Km. However, the addition of fucoidan showed a decrease in Vmax, but no change in Km. To determine whether the stimulatory effect of 6-AH was specifically directed towards glu-plg or streptokinase, the ratios of the initial rate of plasmin generation in the presence of 6-AH over the controls were plotted against the inverse of the volume fraction of glu-plg or streptokinase after serial dilutions. The results indicated that the dilutions of glu-plg, but not of streptokinase, influenced the ratios, suggesting an interaction of 6-AH with glu-plg. Similar experiments were conducted to determine the mechanism of inhibition of streptokinase by fucoidan. The results indicated that fucoidan was interacting with streptokinase, but not with glu-plg. Circular dichroism studies of glu-plg in the near-ultraviolet spectra (250-308 nm) showed that addition of 6-AH enhanced the spectra in the region around certain chromophores, which reflected conformational changes. On the contrary, the far-ultraviolet spectra were almost identical.