Inactivation of glucose-6-phosphate dehydrogenase by 4-hydroxy-2-nonenal. Selective modification of an active-site lysine

L. I. Szweda, K. Uchida, L. Tsai, E. R. Stadtman

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268 Scopus citations

Abstract

Incubation of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides with 4-hydroxy-2-nonenal (HNE) results in a pseudo first-order loss of enzyme activity. The pH dependence of the inactivation rate exhibits an inflection around pH 10, and the enzyme is protected from inactivation by glucose 6-phosphate. Loss of enzyme activity corresponds with the formation of one carbonyl function per enzyme subunit and the appearance of a lysine- HNE adduct. The data presented in this paper are consistent with the view that the ε-amino group of a lysine residue in the glucose 6-phosphate- binding site reacts with the double bond (C3) of HNE, resulting in the formation of a stable secondary amine derivative and loss of enzyme activity. We have described a mechanism by which HNE may, in part, mediate free radical damage. In addition, a method for the detection of the lysine-HNE adduct is introduced.

Original languageEnglish (US)
Pages (from-to)3342-3347
Number of pages6
JournalJournal of Biological Chemistry
Volume268
Issue number5
StatePublished - Jan 1 1993

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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