TY - JOUR
T1 - Reactions of 4-hydroxy-2(E)-nonenal and related aldehydes with proteins studied by carbon-13 nuclear magnetic resonance spectroscopy
AU - Amarnath, Venkataraman
AU - Valentine, William M.
AU - Montme, Thomas J.
AU - Patterson, William H.
AU - Amarnath, Kalyani
AU - Bassett, Casey N.
AU - Graham, Doyle G.
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
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U2 - 10.1021/tx970176n
DO - 10.1021/tx970176n
M3 - Article
C2 - 9548802
AN - SCOPUS:0031924992
SN - 0893-228X
VL - 11
SP - 317
EP - 328
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 4
ER -