The effect of 6-aminohexanoic acid and fucoidan on the activation of glutamic plasminogen by streptokinase.
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.
Harris
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Chemistry Department of Prairie View A University, Texas 77446, USA.
Doctor
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VM
D015119:Aminocaproic Acid / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D010958:Plasminogen / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology; D013300:Streptokinase / Q000187:drug effects / Q000378:metabolism*
D000925:Anticoagulants; D011134:Polysaccharides; D012965:Sodium Chloride; D010958:Plasminogen; C007789:fucoidan; D013300:Streptokinase; D015119:Aminocaproic Acid