Question

How is chymotrypsinogen converted to chymotrypsin in the duodenum? What is the name of this process?

Hint:

Zymogen activation is irreversible. Once trypsin and chymotrypsin are activated in the intestinal lumen, they can only be inactivated by degradation or specific protease inhibitors.

Answer 1

Step 1: Concept
Proteolytic enzymes are synthesized in the pancreas as inactive precursors, called zymogens, to prevent them from digesting the pancreas's own cell proteins during transport.

Step 2: Activation Mechanism in the Duodenum
1. Initial Cleavage: In the duodenum, the enzyme trypsin cleaves a single peptide bond between Arg15 and Ile16 in inactive chymotrypsinogen.
2. Intermediate Formation: This cleavage generates $\pi$-chymotrypsin, which is active but unstable.
3. Autolytic Cleavage: $\pi$-chymotrypsin molecules then undergo autolysis (self-cleavage) to remove two dipeptides: Ser14--Arg15 and Thr147--Asn148.
4. Active Enzyme: This results in $\alpha$-chymotrypsin, the stable active enzyme. It consists of three polypeptide chains held together by two interchain disulfide bonds.


Step 3: Name of the Process
This process is called Zymogen Activation (or Proteolytic Activation Limited Proteolysis). Final Answer: Trypsin cleaves inactive chymotrypsinogen between Arg15 and Ile16, followed by autolytic removal of two dipeptides to produce active three-chain $\alpha$-chymotrypsin. This process is called zymogen activation.