Serine Proteinases from the Blood Coagulation Cascade

2020 ◽  
pp. 395-422
Author(s):  
Herman Schreuder ◽  
Hans Matter
Keyword(s):  
Blood Coagulation ◽  
Coagulation Cascade ◽  
Serine Proteinases

Differential Drug Target Selection in Blood Coagulation: What can we get from Computational Systems Biology Models?

2020 ◽  
Vol 26 (18) ◽  
pp. 2109-2115 ◽  
Author(s):  
Mikhail A. Panteleev ◽  
Anna A. Andreeva ◽  
Alexey I. Lobanov
Keyword(s):  
Blood Coagulation ◽  
Biological Network ◽  
Target Selection ◽  
Anticoagulation Therapy ◽  
Differential Regulation ◽  
Coagulation Cascade ◽  
Computational Systems Biology ◽  
Analysis Strategies ◽  
Optimal Target ◽  
Computational Systems

Discovery and selection of the potential targets are some of the important issues in pharmacology. Even when all the reactions and the proteins in a biological network are known, how does one choose the optimal target? Here, we review and discuss the application of the computational methods to address this problem using the blood coagulation cascade as an example. The problem of correct antithrombotic targeting is critical for this system because, although several anticoagulants are currently available, all of them are associated with bleeding risks. The advantages and the drawbacks of different sensitivity analysis strategies are considered, focusing on the approaches that emphasize: 1) the functional modularity and the multi-tasking nature of this biological network; and 2) the need to normalize hemostasis during the anticoagulation therapy rather than completely suppress it. To illustrate this effect, we show the possibility of the differential regulation of lag time and endogenous thrombin potential in the thrombin generation. These methods allow to identify the elements in the blood coagulation cascade that may serve as the targets for the differential regulation of this system.

scholarly journals Bioactive Lipids Metabolites in Amanita Virosa

2012 ◽  
Vol 7 (11) ◽  
pp. 1934578X1200701 ◽  
Author(s):  
Francesca Cateni ◽  
Marina Zacchigna ◽  
Bojan Doljak ◽  
Marko Anderluh ◽  
Giuseppe Procida ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Blood Coagulation ◽  
Inhibitory Activity ◽  
Complex Mixture ◽  
Serine Proteinase ◽  
Coagulation Cascade ◽  
Bioactive Lipids ◽  
Thrombin Inhibition ◽  
Suitable Target

Thrombin is the key serine proteinase of the coagulation cascade and, therefore, a suitable target for inhibition of blood coagulation. An extract of Amanita virosa considerably inhibited thrombin (48%), but showed no inhibitory activity on trypsin. On the basis of inhibition selectivity between thrombin and trypsin and potency of thrombin inhibition, A. virosa constitutes a good starting material for the isolation of further compounds that are active against thrombin. Bioassay oriented fractionation of the extract of A. virosa led to the isolation of a complex mixture of triglycerides (TGs), monoacylglycerols (MAGs), free fatty acids (FAs) and ergosterol. The structures of the isolated lipids metabolites were determined on the basis of chemical and spectroscopic evidences.

scholarly journals Inhibitory Potency ofErythrina variegataProteinase Inhibitors toward Serine Proteinases in the Blood Coagulation and Fibrinolytic Systems

1996 ◽  
Vol 60 (8) ◽  
pp. 1383-1385 ◽  
Author(s):  
Tomohiro Nakagaki ◽  
Yuko Shibuya ◽  
Yoshiaki Kouzuma ◽  
Nobuyuki Yamasaki ◽  
Makoto Kimura
Keyword(s):  
Blood Coagulation ◽  
Serine Proteinases ◽  
Inhibitory Potency
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