ENZYME CASCADES BLOOD CLOTTING - University of 血凝酶级联大学.ppt

ENZYME CASCADES: BLOOD CLOTTING Medical Biochemistry, Lecture 27 Lecture 27, Outline The extrinsic and intrinsic clotting pathways Specific reactions in the coagulation pathway: a. thrombin-fibrinogen-fibrin; b. Factor XIIIa; c. Hemophilia; d. anti-protease system; e. auto-regulation of thrombin; f. fibrinolysis Blood Clotting Because of the importance of blood in regulating pH and the transport of oxygen, nutrients, carbon dioxide, and wastes, maintaining the integrity of the process is crucial to life. When ruptures in the system do occur, the process of blood clotting is initiated as an emergency measure to halt the loss of blood. Biochemically, blood clotting is an example of signal amplification caused by the simultaneous activation and inhibition of many enzymes. A basic overview of the process and how the enzymes are regulated will be the focus of this lecture. PLEASE REMEMBER Do not worry about memorizing the whole pathway and all of the factors involved - you will be tested on specific examples, not the entire pathway - the focus will be on using this pathway to illustrate all of the interactions between proteins, enzymes and regulatory mechanisms described in the preceding lectures. Blood Vessel Damage When injury to a blood vessel occurs, three major events happen to rapidly stop the loss of blood: 1) clumping of blood platelets at the site of injury to create a physical plug. 2) vasoconstriction occurs to reduce blood flow through the area. 3) aggregation of fibrin into an insoluble clot that covers the rupture and stops loss of blood. The clot is dissolved after actual repair of the blood vessel. Platelet Aggregation The initial phase of platelet aggregation is a complex formed between the platelets and underlying collagen fibrils exposed in the ruptured vessel. An additional circulating protein, von Willebrand factor (vWF), mediates binding of platelets to collagen and each other resulting in activation of the platelets and release of various