Effect of heparin on the inhibition of the contact system enzymes.
1. One can accurately predict the contribution of each inhibitor to the total inactivation of an enzyme in plasma once its pseudo-first-order reaction rate constant and concentration are known. 2. Because the mechanism of augmentation of the inactivation rate of an enzyme by ATIII occurs via formation of an ATIII-heparin complex, the degree of potentiation can be predicted by knowing the binding capacity (sites per mole) of the heparin preparation and the concentration of heparin in the reaction (to calculate the concentration of the ATIII-heparin complex). 3. The augmentation by heparin of the inactivation rate of a particular enzyme by ATIII is dependent upon the presence of other enzymes with higher kassoc, since these would strongly compete for the ATIII-heparin complex. 4. In a plasma environment, using therapeutic levels of heparin, there is no augmentation of the inactivation rate of any of the contact enzymes.
Colman
R W
RW
Thrombosis Research Center, Temple University Health Science Center, Philadelphia, Pennsylvania 19140.
Scott
C F
CF
Pixley
R A
RA
de la Cadena
R A
RA
D000990:Antithrombin III / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D005172:Factor XI / Q000037:antagonists & inhibitors*; D005174:Factor XII / Q000037:antagonists & inhibitors; D015956:Factor XIIa; D015945:Factor XIa; D015951:Factor Xa; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D007610:Kallikreins / Q000037:antagonists & inhibitors; D007700:Kinetics; D015842:Serine Proteinase Inhibitors; D013917:Thrombin / Q000037:antagonists & inhibitors
D015842:Serine Proteinase Inhibitors; D000990:Antithrombin III; D005174:Factor XII; D006493:Heparin; D005172:Factor XI; D007610:Kallikreins; D015945:Factor XIa; D015956:Factor XIIa; D013917:Thrombin; D015951:Factor Xa