Why is trypsin inhibitor present if trypsin is already secreted in form of trypsinogen?

Question

I was reading pancreatic digestive enzymes from a Textbook of Medical Physiology and I came across Trypsin Inhibitor, it stated that It is important that the proteolytic enzymes of the pancreatic juice not become activated until after they have been secreted into the intestine because the trypsin and the other enzymes would digest the pancreas itself.... ....substance called trypsin inhibitor. This substance is formed in the cytoplasm of the glandular cells, and it prevents activation of trypsin both inside the secretory cells and in the acini and ducts of the pancreas.

It also states that 'When first synthesized in the pancreatic cells, the proteolytic digestive enzymes are in the inactive forms trypsinogen, chymotrypsinogen, and procarboxypolypeptidase, which are all inactive enzymatically. They become activated only after they are secreted into the intestinal tract.'

My question is, why is Trypsin Inhibitor secreted if trypsin is already secreted as trypsinogen and can only be activated in intestine.

Answer 1

This excellent description of the pathophysiology of digestion answers your question by explaining in more detail how trypsinogen gets from the pancreas to the intestinal lumen.

"Several proteases are synthesized in the pancreas and secreted into the lumen of the small intestine. The two major pancreatic proteases are trypsin and chymotrypsin, which are synthesized and packaged into secretory vesicles as the inactive proenzymes trypsinogen and chymotrypsinogen.

As you might anticipate, proteases are rather dangerous enzymes to have in cells, and packaging of an inactive precursor is a way for the cells to safely handle these enzymes. The secretory vesicles also contain a trypsin inhibitor which serves as an additional safeguard should some of the trypsinogen be activated to trypsin; [bolded for emphasis] following exocytosis this inhibitor is diluted out and becomes ineffective - the pin is out of the grenade.

Once trypsinogen and chymotrypsinogen are released into the lumen of the small intestine, they must be converted into their active forms in order to digest proteins. Trypsinogen is activated by the enzyme enterokinase, which is embedded in the intestinal mucosa."

The source of this quotation is an online pathophysiology textbook from Colorado State University with this hyperlink.

https://www.vivo.colostate.edu/hbooks/pathphys/digestion/pancreas/exocrine.html

It is possible for trypsinogen to be prematurely activated in the pancreatic interstitium and this can lead to pancreatitis. https://pubmed.ncbi.nlm.nih.gov/10Pa576341/

Packaging the trypsinogen with an inhibitor provides "extra protection" for the pancreas.