Kinetics of the inhibition of plasmin in acidified human plasma.
Acid-treated human plasma is a competitive inhibitor of the hydrolysis of D-Val-Leu-Lys-Nan (S-2251) by plasmin. The rate of hydrolysis is decreased to 50% by 750 fold diluted acidified normal plasma and by 60 fold diluted acidified alpha 2-antiplasmin depleted plasma (alpha 2-antiplasmin concentration less than 2%). These findings suggest that alpha 2-antiplasmin is a contributary but not the main competitive inhibitor of acidified plasma. This interpretation is supported by the finding that alpha 2-antiplasmin depleted plasma reconstituted with purified alpha 2-antiplasmin inhibits the hydrolysis of S-2251 by plasmin at a 125 fold dilution following acidification and by the finding that in a purified system acid inactivated alpha 2-antiplasmin inhibits the hydrolysis of S-2251 by plasmin with a Ki of 25 nM. Thus, besides alpha 2-antiplasmin, other plasma proteins which are at least in part eliminated by the removal of alpha 2-antiplasmin from plasma by immunoadsorption appear to be competitive inhibitors for plasmin in acidified plasma. It is suggested that several competitive inhibitors for plasmin are present and/or generated in acidified plasma and that these inhibitors may at least in part be responsible for the variability in the results of measurements of plasminogen and/or plasmin in plasma following acidification.
D005341:Fibrinolysin / Q000037:antagonists & inhibitors*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009842:Oligopeptides; D000979:alpha-2-Antiplasmin / Q000378:metabolism*
D009842:Oligopeptides; D000979:alpha-2-Antiplasmin; C018788:valyl-leucyl-lysine 4-nitroanilide; D005341:Fibrinolysin