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May 1, 1992Chemical Research in Toxicology

Inactivation of .alpha.1-proteinase inhibitor by peroxynitrite

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Authors

JMJuan MorenoLouisiana State UniversityWPWilliam A. PryorPennington Biomedical Research Center

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Implication

In vitro assay shows peroxynitrite inactivates alpha 1-proteinase inhibitor by selectively oxidizing active-site methionine, indicating a mechanism for smoke-induced lung injury.

Key Points

  • Investigate the chemical mechanism by which peroxynitrite reacts with and inactivates alpha 1-proteinase inhibitor (alpha 1PI) and its active-site decapeptide.
  • Exposed alpha 1PI and a synthetic active-site decapeptide (MER10) to peroxynitrite at pH 7.4 and pH 12.0.
  • Evaluated protection against inactivation using scavengers and amino acids, including thiourea, methionine, mannitol, and benzoate.
  • Characterized reaction products and site modifications using NMR, mass spectrometry, and amino acid analysis.
  • Peroxynitrite inactivated alpha 1PI at both neutral (pH 7.4) and alkaline (pH 12.0) conditions.
  • Inactivation was prevented by thiourea and methionine, whereas mannitol and benzoate failed to confer effective protection.
  • Structural analysis of MER10 demonstrated direct oxidation of the active-site methionine residue without peptide cleavage or phenylalanine modification, occurring independently of hydroxyl radicals or nitrogen dioxide.

Cite This Study

Moreno et al. (1992) studied this question.

synapsesocial.com/papers/6a7d403d0ae9e6500d83dd57https://doi.org/10.1021/tx00027a017
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