Blood clotting enzyme Essay

Serine proteolytic enzyme proteins ar important enzymes baffling in the carry out of transmission line coagulation. family coagulation is an importance defense machine that foils the host mammal organism from losing extravagance blood or from forming unwanted blood clot. The process of coagulation asshole be initiated by some(prenominal)(prenominal) intrinsic work outs and extraneous operators. A go down of event is fol humbleded which aerate these enzymes normally the enzymes are in industrious land a condition called zymogens.Zymogens by their practical(prenominal) condition of being inactive prevent unwanted blood clotting which whitethorn have a far ambit consequence such as thrombosis. breed clotting in a series of processes, in which the zymogens need to be unrestrained by reacting with its glycoprotein co-factors. Among the serine protease is the thrombin enzyme factor five (v) responsible for clearing clot in the blood. The enzyme is usually present ci rculating in plasma which is make up of a single monomer chain, it life span shadower range from 12 to 36 hours.In human the main regulator in blood coagulation is erythrocytes leukemia cubicles which activate adenylate cyclase, the process is reversible by the fundamental fundamental interaction of Aalpa-thrombin with glycoprotein com smear b alpha enhance the thrombocytes interaction which initiate the proteolytic process. Fibrin-bound thrombin is cleaved by thrombin at a very particular proposition situate at the extra kioskular N-terminal, PAR-1 regulates a add of closingothelial cellphone biology, vascular organic evolution but more so is a mediator of thrombin signaling.The human thrombin consist of 2 da Gamma chains namely the gamma A and gamma the final piece of coagulation of mammalian blood involves the division of the four arginine and genus Glycine bond. Binding studies shows both fibrin 1 and fibrin 2 with low family relationship to the E domain and high top affinity at the extreme end of 408 to 425 on the gamma chain The elan of action involves conversion of fibrinogen to fibrin by breaking the bonds in the fibrinogen at a precise position of arginine and genus Glycine where the fibrin peptides are released.The serine proteases require restructuring itself in order to fit the key and lock model. The glycine at the position five is extremely conserved because it is the one which occupy the active site which is moderate by the acryl conference during the substrate con make-up. Asparagines 189 help the enzyme to easily differentiate the substrate. The active site is entirely made of histidine 57, asparagines 102, serine 195 and serine 214.The reaction on many a times prefers position 1 to position 4 during remodeling, therefore the type of protein comportment to a large extend determine the gracious protease and also the kind of cleavage to take place. Thrombin activating is correct by pentapeptide of the COOH terminus of the factor (v) severe chains. Thrombin and thrombin receptors is another regulatory point where they both posses beefed-up protective barrier and at the same time cancerous cells were eliminated by apoptosis. A study carried out apply mitochondrial membranes which were depolarized use attenuated Catalase lead to controlled cell death.Statistical finding indicate that 30% of the population carried world wide indicated that mad peptide segment at position 4 of factor eight caused a reversal in V34L after binding the bodily structure and analyzing the interaction according to (Brenda 2010). The switching of receptor is PAR-1-dependent signaling specifically to thrombin issuanceing inhibition of affection cell go forth which activate thrombin the ligand occupancy position switches the protease receptor by signaling specifically to the thrombin.Human cell in culture indicated low join of thrombin and receptor PAR-1 agonist induced strong anti-inflammatory activities which was se condary effect of the low concentration of thrombin after activation by P13 kinase and PAR-1. Thrombin like other enzymes is very specific in the binding domain and the initiation loop which is determined by the residues intricate in ligand binding as result of interaction glycoprotein and protease receptor on the platelet membrane. This uniqueness makes it very efficacious in it task according to (Webert 2006).The enzyme bleed vital role in homeostasis, cell differentiation, thrombosis and activation of blood cell types, on exposure to phosphatidylserine on the outer surface the platelets were stimulated. A study done using heparin indicated an overlap of the active site, which was attributed to the interaction of thrombin and the gamma peptide chains to the external and the interaction to the active site in keep out proximity to the Na+ of the substrate. The role of the enzyme can be explained in terms of NA+ binding to thrombin on the basis of prothrombotic and procoagulant .The cascade is a continuous cycle of events that are activated by two factors ,factor (ix) and factor (viii) to form tenase complex which is discontinued by down regularisation that occur in the following mechanism which include serpin (serine protease inhibitors) which function to degrade thrombin and other activation factors, it can also be set by protein C where thromodulin bind to it and is deactivate in the presence of protein S, limiting the action of waver factor by the tissue factor pathway inhibitors by inhibiting riotous TF mediated activation of factor (ix) and factor (x), plasmin help to degrade fibrin and so preventing more fibrin being formed and lastly but not the least regulation through adenylate cyclase pathway by inhibiting platelet activation by decreasing cytosol level of calcium which ultimately result to diminish release of granules which are responsible for the activation of more platelets and coagulation cascade. In mop up the work play by thrombin enzyme is of overriding importance considering the complexity of the enzyme kinetics complicated in the human body.References Brenda Enzyme database retrieved on 13 August 2010 from http//www. brenda-enzymes. org/php/result_flat. php4? ecno=3. 4. 21. 5 Furie B, Furie BC (2005). Thrombus formation in vivo. J. Clin. Invest. cxv (12) retrieved on 12 August 2010 from http//www. jci. org/cgi/content/full/115/12/3355. Webert KE, Cook RJ, Sigouin CS, (2006). The risk of exhaust in thrombocytopenic patients with acute myeloid leukemia. haematologica .