Reactions of 4-hydroxy-2(E)-nonenal and related aldehydes with proteins studied by carbon-13 nuclear magnetic resonance spectroscopy

Venkataraman Amarnath, William M. Valentine, Thomas J. Montme, William H. Patterson, Kalyani Amarnath, Casey N. Bassett, Doyle G. Graham

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

In order to understand the modifications of proteins produced by aldehydes of lipid peroxidation, [1-13C]-2(E)-hexenal, [1-13C]-4- oxopentanal, and a mixture of [1-13C]- and [2-13C]4-hydroxynon-2(E)-enal were synthesized and the reaction of each of the labeled aldehydes with bovine serum albumin was analyzed by 13C NMR spectroscopy. Protein nucleophiles add to the 3-position of hexenal, and the resulting propanal moieties appear to undergo aldol condensation, form imine cross-links with lysyl residues, or lead to pyridinium rings. During the reaction of 4- oxopentanal with the lysyl residues of bovine serum albumin, only 1-alkyl-2- methylpyrrole and a possible intermediate leading to the pyrrole were observed. Hydroxy-pyrrolidine cross-links such as 25 could not be detected, leaving the pyrrole as the mediator of protein cross-linking. The Michael adducts are the major products in the reaction between 4-hydroxynon-2-enal and proteins. They exist almost exclusively in the cyclic hemiacetal form and do not appear to cross-link through imine formation with lysyl residues. A minor pathway involves the reaction of 4-hydroxynon-2-enal with the lysyl amino groups of protein resulting in 2-pentylpyrrole adducts that may mediate protein cross-linking. The Michael adducts appear not to be the direct source of the pyrrole, but the imine 32 and the enamine 35 are likely intermediates toward the five-membered ring.

Original languageEnglish (US)
Pages (from-to)317-328
Number of pages12
JournalChemical Research in Toxicology
Volume11
Issue number4
DOIs
StatePublished - May 11 1998
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology

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