Trypsinogen stabilization by mutation Arg117→His: A unifying pathomechanism for hereditary pancreatitis?

Miklós Sahin-Tóth, L. Gráf, Miklós Tóth

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Mutations Arg117→His and Asn21→Ile of the human cationic trypsinogen have been recently identified in patients affected by hereditary pancreatitis (HP). The Arg117→His substitution is believed to cause pancreatitis by eliminating an essential autolytic cleavage site in trypsin, thereby rendering the protease resistant to inactivation through autolysis. Here we demonstrate that the Arg117→His mutation also significantly inhibits autocatalytic trypsinogen breakdown under Ca2+-free conditions and stabilizes the zymogen form of rat trypsin. Taken together with recent findings demonstrating that the Asn21→Ile mutation stabilizes rat trypsinogen against autoactivation and consequent autocatalytic degradation, the observations suggest a unifying molecular pathomechanism for HP in which zymogen stabilization plays a central role.

Original languageEnglish
Pages (from-to)505-508
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume264
Issue number2
DOIs
Publication statusPublished - Oct 22 1999

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Trypsinogen
Enzyme Precursors
Stabilization
Trypsin
Mutation
Rats
Autolysis
Pancreatitis
Peptide Hydrolases
Substitution reactions
Degradation
Hereditary pancreatitis

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Trypsinogen stabilization by mutation Arg117→His : A unifying pathomechanism for hereditary pancreatitis? / Sahin-Tóth, Miklós; Gráf, L.; Tóth, Miklós.

In: Biochemical and Biophysical Research Communications, Vol. 264, No. 2, 22.10.1999, p. 505-508.

Research output: Contribution to journalArticle

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