Thrombin

By: Bailey Goodyear, Mike Kiefer, Yami Hernandez

Location of thrombin production

• Prothrombin is produced in the: liver• Prothrombin is then converted into thrombin.• Thrombin is an enzyme not a hormone.

Function

• Thrombin converts fibrinogen into fibrin.• Fibrin is the mesh-like material that aids in

blood clotting by forming a mesh that traps red blood cells.

• Thrombin activation also leads to activation of clotting factors, like Factor IV and platelets, and immune response cells, like lymphocytes and monocytes.

Pathway

Thrombin from the bloodstream binds to PARs (Protease Activated Receptors) which function as G-Protein Coupled Receptors, passing the signal on using G-Proteins that begin a Phosphorylation Cascade. The Phosphorylation Cascade leads to a protein called P13K. P13K activates two other proteins that finally synthesize the activation of four transcription factors.

Pathway Results

The transcription factors transcribe genes for:• Cell growth/division • Platelet aggregation and blood coagultion • Angiogenesis, the formation of new blood

vessels from existing vessels• Cell adhesion

Cellular Response

• Fibrinogen is converted into fibrin which forms web-like structures that trap RBCs and platelets, allowing clots to form. The clots help the injury to heal and prevent foreign pathogens or materials from entering the wound.

Feedback

• Positive Feedback • Thrombin activation results primarily in fibrin

production, but also begins a cascade of activations of clotting factors like Factor V or Factor VIII. The cascade forms a feedback loop in which some of the proteins that are activated then activate thrombin production.

Pathway Alteration

• Thrombophilia is abnormality that can result in blood clots within blood vessels, also known as thrombosis. Thrombosis can block arteries, causing hypoxia, deprivation of oxygen to cells, and the build up of lactic acid.

• It is caused by the Prothrombin G20210A mutation, a point mutation, replacing guanine with adenine, in a noncoding region of the prothrombin gene.