Carboxylate polyanions accelerate inhibition of thrombin by heparin cofactor II.
The heparin cofactor II (HCII)/thrombin inhibition reaction is enhanced by various carboxylate polyanions. In the presence of polyaspartic acid, the HCII/thrombin reaction is accelerated more than 1000-fold with the second-order rate constant increasing from 3.2 x 10(4) M-1 min-1 (in the absence of polyAsp) to 3.6 x 10(7) M-1 min-1 as the polyAsp concentration is increased from 1 to 250 micrograms/ml. This accelerating effect was observed for HCII/thrombin, though to varying degrees, with other carboxylate polyanions. In contrast to HCII, the rate of antithrombin III inhibition of thrombin was decreased in the presence of polyAsp. The HCII/thrombin complex is rapidly formed in the presence of 10 micrograms/ml polyAsp when 125I-labeled-thrombin is incubated with plasma. It is possible that at physiological sites rich in carboxylate polyanions, thrombin may be preferentially inhibited by HCII.
Church
F C
FC
Department of Medicine, University of North Carolina at Chapel Hill 27514.
Treanor
R E
RE
Sherrill
G B
GB
Whinna
H C
HC
D000838:Anions; D000991:Antithrombins / Q000494:pharmacology*; D004357:Drug Synergism; D006023:Glycoproteins / Q000494:pharmacology*; D015844:Heparin Cofactor II; D007700:Kinetics; D010455:Peptides / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013917:Thrombin / Q000378:metabolism
D000838:Anions; D000991:Antithrombins; D006023:Glycoproteins; D010455:Peptides; D015844:Heparin Cofactor II; D013917:Thrombin