PHYSIOLOGY SEMINAR
Topic : Enzyme Cascade Theory (ECT)
Prepared By : Uzair Kuraishi
Roll number : 31
Guided By : Dr.Gaurav Sir
Department of Physiology
ENZYME
CASCADE
THEORY
Introduction:
• The classic theory of coagulation was described by Paul Morawitz in 1905.
• This theory described each clotting factor as an inactive proenzyme which will
further converted to active enzyme to enforce clot formation.
• This theory is series of biochemical reactions.
• A fibrin clot is the end product of this enzyme cascade theory.
• There are 3 stages of Blood Clotting
1. Formation of prothrombin activator
2. Conversion of prothrombin into thrombin
3. Conversion of fibrinogen into fibrin
• Stage 1 : Formation of prothrombin activator
• Blood clotting commences with the formation of a substance called prothrombin
activator, which converts prothrombin into thrombin.
• Its formation is initiated by substances produced either within the blood or
outside the blood.
• Formation of prothrombin activator occurs through two pathways:
i. Intrinsic pathway
ii. Extrinsic pathway
Intrinsic Pathway for prothrombin activator:
• In this pathway, the formation of prothrombin activator is initiated by platelets, which
are within the blood itself.
Sequence of events in intrinsic pathway
i. During the injury, the blood vessel is ruptured.Endothelium is damaged and
collagen beneath the endothelium is exposed.
ii. When factor XII comes in contact with collagen, it is converted into activated factor
XII in the presence of kallikrein and high molecular weight (HMW) kinogen.
iii. The activated factor XII converts factor XI into activated factor XI in the presence
of HMW kinogen.
iv. The activated factor XI activates factor IX in the presence of factor IV.
v. Activated factor IX activates factor X in the presence of factor VIII and calcium.
vi. When platelet comes in contact with collagen of damaged blood vessel, it gets
activated and releases phospholipids.
vii. Now the activated factor X reacts with platelet phospholipid and factor V to form
prothrombin acti-vator. This needs the presence of calcium ions.
viii. Factor V is also activated by positive feedback effect of thrombin.
Extrinsic Pathway for the Formation of Prothrombin Activator:
• In this pathway, the formation of prothrombin activator is initiated by the tissue thromboplastin,
which is formed from the injured tissues.
Sequence of events in extrinsic pathway
i. Tissues that are damaged during injury release tissue thromboplastin (factor III).
Thromboplastin contains proteins, phospholipid and glycoprotein, which act as proteolytic
enzymes.
ii. Glycoprotein and phospholipid components of thromboplastin convert factor X into activated
factor X, in the presence of factor VII.
iii. Activated factor X reacts with factor V and phospholipid component of tissue thromboplastin to
form prothrombin activator. This reaction requires the presence of calcium ions.
• Stage 2 : Conversion of Prothrombin into Thrombin
• Blood clotting is all about thrombin formation. Once thrombin is formed, it
definitely leads to clot formation.
Sequence of Events in Stage 2
i. Prothrombin activator that is formed in intrinsic and extrinsic pathways
converts prothrombin into thrombin in the presence of calcium (factor IV).
ii. Once formed thrombin initiates the formation of more thrombin molecules. The
initially formed thrombin activates Factor V. Factor V in turn accelerates
formation of both extrinsic and intrinsic prothrombin activator, which converts
prothrombin into thrombin. This effect of thrombin is called positive feedback
effect.
• Stage 3 : Conversion of Fibrinogen into Fibrin
• The final stage of blood clotting involves the conversion of fibrinogen into fibrin
by thrombin.
Sequence of Events in Stage 3
i. Thrombin converts inactive fibrinogen into activated fibrinogen due to loss of 2
pairs of polypeptides from each fibrinogen molecule. The activated fibrinogen
is called fibrin monomer.
ii. Fibrin monomer polymerizes with other monomer molecules and form loosely
arranged strands of fibrin.
iii. Later these loose strands are modified into dense and tight fibrin threads by
fibrin-stabilizing factor (factor XIII) in the presence of calcium ions. All the tight
fibrin threads are aggregated to form a meshwork of stable clot.
