Carnosine is a quencher of 4-hydroxy-nonenal: through what mechanism of reaction?
The aim of this study was to understand the mechanism of action through which carnosine (β-alanyl- l-histidine) acts as a quencher of cytotoxic α,β-unsaturated aldehydes, using 4-hydroxy- trans-2,3-nonenal (HNE) as a model aldehyde. In phosphate buffer solution (pH 7.4), carnosine was 10 times more...
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Published in | Biochemical and biophysical research communications Vol. 298; no. 5; pp. 699 - 706 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
15.11.2002
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Subjects | |
Online Access | Get full text |
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Summary: | The aim of this study was to understand the mechanism of action through which carnosine (β-alanyl-
l-histidine) acts as a quencher of cytotoxic α,β-unsaturated aldehydes, using 4-hydroxy-
trans-2,3-nonenal (HNE) as a model aldehyde. In phosphate buffer solution (pH 7.4), carnosine was 10 times more active as an HNE quencher than
l-histidine and
N-acetyl-carnosine while β-alanine was totally inactive; this indicates that the two constitutive amino acids act synergistically when incorporated as a dipeptide and that tshe β-alanyl residue catalyzes the addition reaction of the histidine moiety to HNE. Two reaction products of carnosine were identified, in a pH-dependent equilibrium: (a) the Michael adduct, stabilized as a 5-member cyclic hemi-acetal and (b) an imine macrocyclic derivative. The adduction chemistry of carnosine to HNE thus appears to start with the formation of a reversible α,β-unsaturated imine, followed by ring closure through an intra-molecular Michael addition. The biological role of carnosine as a quencher of α,β-unsaturated aldehydes was verified by detecting carnosine-HNE reaction adducts in oxidized rat skeletal muscle homogenate. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/S0006-291X(02)02545-7 |