Serine protease proteins are important enzymes involved in the process of blood coagulation. blood coagulation is an importance defense mechanism that prevents the host mammal organism from losing excess blood or from forming unwanted blood clot. The process of coagulation can be initiated by both intrinsic factors and extrinsic factors. A cascade of event is followed which activate these enzymes; normally the enzymes are inactive state a condition called zymogens.
Zymogens by their virtual condition of being inactive prevent unwanted blood clotting which may have a far reaching consequence such as thrombosis. Blood clotting in a series of processes, in which the zymogens’ need to be activated 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 circulating in plasma which is made up of a single monomer chain, it life span can range from 12 to 36 hours.
In human the main regulator in blood coagulation is erythrocytes leukemia cells which activate adenylate cyclase, the process is reversible by the interaction of Aalpa-thrombin with glycoprotein while b alpha enhance the platelets interaction which initiate the proteolytic process. Fibrin-bound thrombin is cleaved by thrombin at a very specific site at the extracellular N-terminal, PAR-1 regulates a number of endothelial cell biology, vascular development but more so is a mediator of thrombin signaling.
Abstract In living organisms, certain reactions must take place rapidly to assist life. This occurs because of enzymes, because all reactions would take place too slowly to sustain life (Jacklet, 237). Enzymes are large protein molecules that catalyze specific chemical reactions without being used up in the process. Each enzyme has a region on its surface, called the active site, which recognizes ...
The human thrombin consist of two gamma chains namely the gamma A and gamma’ the final stage of coagulation of mammalian blood involves the cleavage of the four arginine and glycine bond. Binding studies shows both fibrin 1 and fibrin 2 with low affinity to the E domain and high binding affinity at the extreme end of 408 to 425 on the gamma chain The mode of action involves conversion of fibrinogen to fibrin by breaking the bonds in the fibrinogen at a precise position of arginine and 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 highly conserved because it is the one which occupy the active site which is determine by the acryl group during the substrate conformation. Asparagines 189 help the enzyme to easily recognize 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 presence to a large extend determine the kind protease and also the kind of cleavage to take place. Thrombin activation is regulated by pentapeptide of the COOH terminus of the factor (v) heavy chains. Thrombin and thrombin receptors is another regulatory point where they both posses strong protective barrier and at the same time cancerous cells were eliminated by apoptosis. A study carried out using mitochondrial membranes which were depolarized using attenuated Catalase lead to controlled cell death.
Statistical finding indicate that 30% of the population carried world wide indicated that activated peptide segment at position 4 of factor eight caused a substitution in V34L after binding the structure and analyzing the interaction according to (Brenda 2010).
The switching of receptor is PAR-1-dependent signaling specifically to thrombin resulting inhibition of adhesion cell surface which activate thrombin the ligand occupancy position switches the protease receptor by signaling specifically to the thrombin.
Transcription factors are DNA-binding proteins that regulate several cellular functions including control of the cell cycle, development, cell signaling and transcription. In this study, the AP/ ERF transcription factor (TF) Rap2.4like from Arabidopsis thaliana was characterized in terms of its DNA-binding specificity. PCR constructs of approximately 768-bp in length were designed for integration ...
Human cell in culture indicated low amount of thrombin and receptor PAR-1 agonist induced strong anti-inflammatory activities which was secondary 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 insertion loop which is determined by the residues involved in ligand binding as result of interaction glycoprotein and protease receptor on the platelet membrane. This uniqueness makes it very efficient in it task according to (Webert 2006).
The enzyme play 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 close 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 regulation 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 regulated by protein C where thromodulin bind to it and is inactivate in the presence of protein S, limiting the action of tissue factor by the tissue factor pathway inhibitors by inhibiting excessive TF mediated activation of factor (ix) and factor (x), plasmin help to degrade fibrin hence 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 decreased release of granules which are responsible for the activation of more platelets and coagulation cascade. In conclusion the work play by thrombin enzyme is of paramount importance considering the complexity of the enzyme kinetics involved in the human body.
An enzyme is a protein that speeds up or slows down a specific chemical reaction in an organism. A good rule of thumb is to remember that enzyme names end in “-ase”. This will help in identifying enzymes in further readings. Generally enzymes are catalysts. Hydrogen peroxide is a toxic chemical that is produced in many organisms during metabolism. Organisms must get rid of this toxin to survive. ...
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. 115 (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 bleeding in thrombocytopenic patients with acute myeloid leukemia. haematologica .