Enzyme Regulation II Flashcards
In blood clotting, what is the first response?
First response- Cellular response
Blood Platelets: they start to plug the hole.
In blood clotting, what is the molecular response?
It is a much larger response.
The blood clot is formed here.
What does damage to the epithelial tissue cause?
Damage to epithelial tissue exposes collage. This exposure tells the body that clotting must begin
How do platelets start to make plugs in the cellular response?
Platelets bind collagen-binding surface receptors and these blood cells begin to try and form a plug.
How do the platelet integrin’s (proteins in platelets) affect the site of the wound in the cellular process?
Platelet integrin’s (proteins in platelets) get activated and bind tightly to extracellular matrix (found outside of cells) to anchor to site of wound.
What does the Von Willebrand factor glycoprotein do during the cellular response?
Von Willebrand factor (a blood glycoprotein) forms additional links between platelets’ glycoproteins (on the surface of the cell) and the fibrils of the collagen.
What does the amplification process in the cellular process do?
Amplification begins with release of platelet factor 4 (inhibits heparin (anti-clotting factor)) and tissues release thromboxsane A2 (increases platelet stickiness).
What is released at the end of the cellular response?
Calcium is released from intracellular stores (Gq cascade)
Calcium will play a role in the molecular response.
What is the intrinsic pathway and extrinsic pathway in the Molecular Response? What to they result in?
- Contact activation (intrinsic) pathway
- Tissue factor (extrinsic) pathway
They converges to stimulate the conversion of prothrombin to thrombin, the conversion of fibrinogen to fibrin and the activation of factor 13A to make blood clots.
What pathway is more important in the molecular response
The extrinsic pathway is also known as the tissue factor pathway is more Important.
What occurs in the Initiation Phase of the Molecular response?
What complex formation is stimulated?
Tissue damage stimulates formation of TF-F7A complex
What occurs in the Initiation Phase of the Molecular response?
What does the TF-F7A complex help activate?
TF-FVIIa, FIXa, Platelet Membrane Phospholipid (PL) and calcium (from the cellular response) inefficiently convert FX to FXa
What does FXa and other factors inefficiently convert?
FXa, FV, PL, and calcium inefficiently convert prothrombin (zymogen) to a tiny amount of thrombin.
How what thrombin do to activate the formation of itself?
It activates other factors that promote the activation of itself in the amplification phase.
What is the amplification phase require?
The amplification phase of the molecular response requires factors form both the intrinsic and extrinsic response.
What does the amplification phase start with?
It starts with F8, that is normally bound in a complex with the von Willebrand factor and is inactive until it is released by action of thrombin.
In the amplification phase what does F11a favor?
FXIa favors factors of more FIXa
In the amplification phase what does F9a and F8a favor?
FIXa plus FVIIIa stimulate production of a considerable amount of FXa (3-4 orders of magnitude).
In the amplification phase what does F5a and F10a joined with calcium promote?
FVa joins FXa and calcium to make a much larger amount of thrombin (3-4 orders of magnitude).
When we have a lot of thrombin what occurs?
Converts fibrinogen to fibrin and fibrin assembles itself into long polymers.
How does a clot Harden?
Transglutaminase (FXIIIa) catalyzes the bond between the carboxamide part of glutamine which to the amino of a lysine- Covalent bond.
Creates crosslinked fibrin.
Loss of NH3
What does Prothrombin do?
Converts fibrinogen to fibrin
It is a Serine Protease
Must bind calcium to be at site of wound
Carboxylation of glutamate side chains requires vitamin K. (adding another COO- to create a pocket for Ca++ to bind)
What is Hemophelia disease?
Deficiency of FVIII leads to Hemophilia A, they can’t properly clot their blood so they can bleed to death.
Deficiency of FIX produces Hemophilia B, they can’t properly clot their blood so they can bleed to death.
What is Von Willebrand’s disease?
Binds to FVIII in the molecular response, playing a protective role for it. Makes F8 inactive.
In the absence of von Willebrand factor, FVIII is destroyed.
