The Main Classes F Inhibitors Of The Enzymes Of Coagulation And Fibrinolytic Pathways

Question 1

Describe how the thrombin-thrombomodulin complex can control the coagulation and fibrinolytic pathways

Answer 1

• the complex can activate protein C, which complexes with protein S and degrades the active forms of factor 5 and 8
• the complex controls fibrinolysis by activating thrombin-active fibrinolytic inhibitor (a carboxypeptidase) which cleaves the C-terminals of fibrin so that plasmin is unable to degrade the fibrin mesh

Question 2

What are serpins?

Answer 2

Serine proteinase inhibitors (non-enzymatic)

Question 3

What do serpins control?

Answer 3

Serpins can control either clotting or fibrinolysis through action on different factors

Question 4

Which is the most important serpin

Answer 4

Anti-thrombin III

A major regulator of the clotting cascade

Question 5

What is Anti-thrombin 3 dependant on?

Answer 5

Heparin

Question 6

Explain how ATIII is activated

Answer 6

ATIII is inactive without heparin. When heparin binds, areas of the effector loop (of ATIII) change conformation and the serpin is able to engage with the serine proteinase (thrombin and other factors) and inhibit it

Question 7

What is heparin?

Answer 7

A negatively charged complex carbohydrate

Question 8

Why is heparin given to patients?

Answer 8

In order to promote control and inhibition of clotting

Question 9

What are Kunitz type inhibitiors?

Answer 9

Another class of non-enzyme inhibitors. They are multi domain proteins which contain 1 - 4 K-type modules that work as a lock and key system. They fit into the specificity pockets of serine proteinases, form non-covalent complexes which don’t allow for the binding of the specific substrate