Trypsinogen

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Trypsinogen (

intestinal mucosa. Once activated, the trypsin can cleave more trypsinogen into trypsin, a process called autoactivation. Trypsin cleaves the peptide bond on the carboxyl side of basic amino acids such as arginine and lysine
.

Function

Trypsinogen is the

proenzyme precursor of trypsin. Trypsinogen (the inactive form) is stored in the pancreas so that it may be released when required for protein digestion. The pancreas stores the inactive form trypsinogen because the active trypsin would cause severe damage to the tissue of the pancreas. Trypsinogen is released by the pancreas into the second part of the duodenum, via the pancreatic duct, along with other digestive enzymes.[3]

Activation of trypsinogen

Trypsinogen is activated by enteropeptidase (also known as enterokinase). Enteropeptidase is produced by the

mucosa of duodenum and it cleaves the peptide bond of trypsinogen after residue 15, which is a lysine. The N-terminal peptide is discarded, and a slight rearrangement of the folded protein occurs. The newly formed N-terminal residue (residue 16) inserts into a cleft, where its α-amino group forms an ion pair with the aspartate near the active site serine, and results in the conformational rearrangement of other residues. The amino group of Gly 193 orientates itself into the correct position, which completes the oxyanion hole in active site, thereby activating the protein.[4]
Since trypsin also cleaves the peptide bond after an arginine or a lysine, it can cleave other trypsinogen, and the activation process therefore becomes autocatalytic.

Safeguards against trypsinogen activation

Trypsin is produced, stored and released as the inactive trypsinogen to ensure that the protein is only activated in the appropriate location. Premature trypsin activation can be destructive and may trigger a series of events that lead to pancreatic self-digestion. In normal pancreas, around 5% of trypsinogens are thought to get activated[

aspartate on the back of trypsin's specificity pocket.[5]
Trypsin may also inactivate other trypsin by cleavage.

Serum trypsinogen

Serum trypsinogen is measured using a blood test. High levels are seen in acute pancreatitis[6] and cystic fibrosis.[7]

Trypsinogen isoforms

Three

isoforms of trypsinogens may be found in human pancreatic juice. These are the cationic, anionic, and meso trypsinogen, and they account for 23.1%, 16%, and 0.5% of total pancreatic secretory proteins, respectively.[8]
Other forms of trypsinogen have been found in other organisms.

Diseases

The inappropriate activation of trypsinogen in the pancreas can lead to pancreatitis. Some type of pancreatitis may be associated with mutant forms of trypsinogen. A mutation at Arg 117, a trypsin-sensitive site, in cationic trypsinogen has been implicated in hereditary pancreatitis, a rare form of early-onset genetic disorder. Arg 117 may be a fail-safe mechanism by which trypsin, when activated within the pancreas, may become inactivated, and loss of this cleavage site would result in a loss of control and permit autodigestion resulting in pancreatitis.[9] Other mutations have also been found that are linked to pancreatitis.[10]

References

  1. ^ "Trypsinogen". Lexico UK English Dictionary. Oxford University Press. Archived from the original on 2020-03-22.
  2. ^ "Trypsinogen". Dictionary.com Unabridged (Online). n.d. Retrieved 2016-01-25.
  3. PMID 10576341
    .
  4. ISBN 0-7167-2317-4
    .
  5. ISBN 0-471-58651-X
    .
  6. PMID 30660731
    .
  7. PMID 33526571
    .
  8. PMID 6969677
    .
  9. S2CID 21974705
    .
  10. PMID 21907651
    .

External links
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