Enzyme Regulation II

Question 1

In blood clotting, what is the first response?

Answer 1

First response- Cellular response

Blood Platelets: they start to plug the hole.

Question 2

In blood clotting, what is the molecular response?

Answer 2

It is a much larger response.

The blood clot is formed here.

Question 3

What does damage to the epithelial tissue cause?

Answer 3

Damage to epithelial tissue exposes collage. This exposure tells the body that clotting must begin

Question 4

How do platelets start to make plugs in the cellular response?

Answer 4

Platelets bind collagen-binding surface receptors and these blood cells begin to try and form a plug.

Question 5

How do the platelet integrin’s (proteins in platelets) affect the site of the wound in the cellular process?

Answer 5

Platelet integrin’s (proteins in platelets) get activated and bind tightly to extracellular matrix (found outside of cells) to anchor to site of wound.

Question 6

What does the Von Willebrand factor glycoprotein do during the cellular response?

Answer 6

Von Willebrand factor (a blood glycoprotein) forms additional links between platelets’ glycoproteins (on the surface of the cell) and the fibrils of the collagen.

Question 7

What does the amplification process in the cellular process do?

Answer 7

Amplification begins with release of platelet factor 4 (inhibits heparin (anti-clotting factor)) and tissues release thromboxsane A2 (increases platelet stickiness).

Question 8

What is released at the end of the cellular response?

Answer 8

Calcium is released from intracellular stores (Gq cascade)

Calcium will play a role in the molecular response.

Question 9

What is the intrinsic pathway and extrinsic pathway in the Molecular Response? What to they result in?

Answer 9

1. Contact activation (intrinsic) pathway
2. 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.

Question 10

What pathway is more important in the molecular response

Answer 10

The extrinsic pathway is also known as the tissue factor pathway is more Important.

Question 11

What occurs in the Initiation Phase of the Molecular response?

What complex formation is stimulated?

Answer 11

Tissue damage stimulates formation of TF-F7A complex

Question 12

What occurs in the Initiation Phase of the Molecular response?

What does the TF-F7A complex help activate?

Answer 12

TF-FVIIa, FIXa, Platelet Membrane Phospholipid (PL) and calcium (from the cellular response) inefficiently convert FX to FXa

Question 13

What does FXa and other factors inefficiently convert?

Answer 13

FXa, FV, PL, and calcium inefficiently convert prothrombin (zymogen) to a tiny amount of thrombin.

Question 14

How what thrombin do to activate the formation of itself?

Answer 14

It activates other factors that promote the activation of itself in the amplification phase.

Question 15

What is the amplification phase require?

Answer 15

The amplification phase of the molecular response requires factors form both the intrinsic and extrinsic response.

Question 16

What does the amplification phase start with?

Answer 16

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.

Question 17

In the amplification phase what does F11a favor?

Answer 17

FXIa favors factors of more FIXa

Question 18

In the amplification phase what does F9a and F8a favor?

Answer 18

FIXa plus FVIIIa stimulate production of a considerable amount of FXa (3-4 orders of magnitude).

Question 19

In the amplification phase what does F5a and F10a joined with calcium promote?

Answer 19

FVa joins FXa and calcium to make a much larger amount of thrombin (3-4 orders of magnitude).

Question 20

When we have a lot of thrombin what occurs?

Answer 20

Converts fibrinogen to fibrin and fibrin assembles itself into long polymers.

Question 21

How does a clot Harden?

Answer 21

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

Question 22

What does Prothrombin do?

Answer 22

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)

Question 23

What is Hemophelia disease?

Answer 23

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.

Question 24

What is Von Willebrand’s disease?

Answer 24

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.

Question 25

How does vitamin K help calcium bind to proteins?

Answer 25

Vitamin K-related Modifications Facilitate calcium binding by target proteins.

Involved in Carboxylation of Glutamates of Blood clotting factors

Question 26

What happens when vitamin K is absent in your body?

Answer 26

o Absence of Vitamin K Leads to uncontrolled bleeding.

Question 27

The enzyme that catalyzes the carboxylation of glutamate side chains is called glutamate carboxylase. In the process of carboxylation of glutamate side chains the vitamin K is converted to_____

Answer 27

Vitamin K Epoxide

Question 28

Vitamin K Epoxide has to be converted back to vitamin K or else you would bleed to death. What enzyme converts Vitamin K Epoxide back to vitamin K?

Answer 28

Vitamin K Epoxide Reductase is the enzyme that converts vitamin K Epoxide to vitamin K.

Question 29

What is Warfarin (Coumadin)?

Answer 29

Warfarin (Coumadin) is an inhibitor of Vitamin Epoxide Reductase- This is a blood thinner.

Question 30

How does aspirin work?

Answer 30

Works different from warfarin Reduce clotting, inhibits the production of prostaglandins

Prostaglandins are precursors of thromboxane A2

Thromboxane A2 helps make platelets “sticky” in cellular response.

Question 31

How does plasmin dissolve clots?

Answer 31

Factors activate plasminogen to form plasmin.

It is a serine protease that cleaves fibrin clots, fibronectin, thrombospondin, and the von Willebrand factor