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Comparison of the molecular mass dependency of heparin stimulation of heparin cofactor II:thrombin interaction to antithrombin III:thrombin interaction
Authors:M F Scully  V Ellis  V V Kakkar
Affiliation:1. Department of Geology, Patna University, Ashok Rajpath, Patna 800005, India;2. Department of Engineering, Reykjavik University, Menntavegur 1, 102, 101 Reykjavík, Iceland;3. GRO-GTP, Geothermal Training Programme, Urdarhvarf 8 (B), 203 Kopavogur, Iceland;4. Centre of Excellence for Geothermal Energy, Pandit Deendayal Energy University, Gandhinagar 382007, Gujarat, India;5. Department of Chemical Engineering, School of Technology, Pandit Deendayal Energy University, India;6. Silver Oak College of Engineering and Technology, S.G. Road, Gujarat, India;2. Department of Poultry Production, Faculty of Agriculture, Assiut University, Assiut, 71526, Egypt;3. Animal Production Department, Faculty of Agriculture, Benha University, Moshtohor, 13736, Egypt;4. Guangdong Academy of Agricultural Sciences, Guangzhou, Guangdong, China;1. Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, Guangxi, China;2. International Field Epidemiology Training Program, Bureau of Epidemiology, Ministry of Public Health, Nonthaburi, Bangkok, Thailand;3. Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, HatYai, Songkla, Thailand
Abstract:The influence of increasing concentrations of heparin of different molecular mass (Mr) has been compared in potentiation of the rate of heparin cofactor II:thrombin interaction and of antithrombin III:thrombin interaction. Unfractionated and fractionated heparin showed a concentration dependent ascending and descending limb of stimulation of the rate for both inhibitors. Unfractionated heparin and fractions of 16.5 KDa or less showed a peak acceleration of the rate of interaction of thrombin with both inhibitors at 0.3 X 10(-6) M heparin although the observed maximum rate at this peak decreased with fall in Mr. For both inhibitors two high Mr fractions showed peak stimulation at a lower heparin concentration (0.3 X 10(-7) M) and approximately two-fold greater increase in rate than that observed with unfractionated heparin. Potentiation of heparin cofactor II inhibitory activity differed from that of antithrombin III in that it was reversed by lower ionic strength and was not reversed by a heparin pentasaccharide with high affinity for antithrombin III. It is proposed that differences in the profiles of stimulation by high Mr fractions to those of lower Mr are related to higher binding affinities for the inhibitor permitting maximal binding of heparin before the descending part of the slope due to saturation of thrombin (according to the template hypothesis).
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