Question

In: Chemistry

Although thrombin has many properties in common with trypsin, the conversion of prothrombin to thrombin is...

Although thrombin has many properties in common with trypsin, the conversion of prothrombin to thrombin is not autocatalytic whereas the conversion of trypsinogen to trypsin is autocatalytic. Explain this difference in the activation of these zymogens.

Solutions

Expert Solution

Activation of trypsin:

  • Trypisonogen a zymogen of the pancreatic enzyme trypsin. It is cleaved proteolytically by the enzyme enteropeptidase to from trypsin.
  • Trypsin initiates the production of other proteases and activates other digestive enzyme. The production of trypsin is tightly regulated because when trypsinis produced in the wrong time the intestinal mucosa gets affected by activation of all other digestive
  • To produce active trypsin, the cells that line the duodenum secrete an enzyme, enteropeptidase, that hydrolyzes a unique lysine-isoleucine peptide bond in trypsinogen as the zymogen enters the duodenum from the pancreas.
  • The small amount of trypsin produced in this way activates more trypsinogen and the other zymogens enzyme.

Thrombin activation:

  • Thrombin is also like trypsin a serine protease . Prothrombin is proteolytically cleaved to form thrombin which activates fibrinogen and coagulation cascade .Prothrombin, which comprises four major domains, with the serine protease domain at its carboxyl terminus.
  • The first domain is called a gla domain, whereas domains 2 and 3 are called kringle domains . These domains work in concert to keep prothrombin in an inactive form and to target it to appropriate sites for its activation by a serine protease and a stimulatory protein.
  • Activation is accomplished by proteolytic cleavage of the bond between arginine 274 and threonine 275 to release a fragment containing the first three domains and by cleavage of the bond between arginine 323 and isoleucine 324 to yield active thrombin.

Activation of prothrombin is differet because it is involved in coagulatory mechanism and its activation should be fast compared to other zymogens. Hence the activation is regulated by feed back mechanism.


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