Elucidation of reaction scheme describing malondialdehyde-acetaldehyde-protein adduct formation

Tuma, Dean J., Kearley, Mark L., Thiele, Geoffrey M., Worrall, Simon, Haver, Alvin, Klassen, Lynell W. and Sorrell, Michael F. (2001) Elucidation of reaction scheme describing malondialdehyde-acetaldehyde-protein adduct formation. Chemical Research In Toxicology, 14 7: 822-832. doi:10.1021/tx000222a

Author Tuma, Dean J.
Kearley, Mark L.
Thiele, Geoffrey M.
Worrall, Simon
Haver, Alvin
Klassen, Lynell W.
Sorrell, Michael F.
Title Elucidation of reaction scheme describing malondialdehyde-acetaldehyde-protein adduct formation
Journal name Chemical Research In Toxicology   Check publisher's open access policy
ISSN 0893-228X
Publication date 2001-05
Sub-type Article (original research)
DOI 10.1021/tx000222a
Volume 14
Issue 7
Start page 822
End page 832
Total pages 11
Editor L.J. Marnett
Place of publication Washington , D.C., U.S.A.
Publisher American Chemical Society
Collection year 2001
Language eng
Subject C1
270100 Biochemistry and Cell Biology
730118 Organs, diseases and abnormal conditions not elsewhere classified
Abstract Malondialdehyde and acetaldehyde react together with proteins and form hybrid protein conjugates designated as MAA adducts, which have been detected in livers of ethanol-fed animals. Our previous studies have shown that MAA adducts are comprised of two distinct products. One adduct is composed of two molecules of malondialdehyde and one molecule of acetaldehyde and was identified as the 4-methpl-1,4-dihydropyridine-3,5-dicarbaldehyde derivative of an amino group (MHHDC adduct). The other adduct is a 1:1 adduct of malondialdehyde and acetaldehyde and was identified as the 2-formyl-3-(alkylamino)butanal derivative of an amino group (FAAB adduct). In this study, information on the mechanism of MAA adduct formation was obtained, focusing on whether the FAAB adduct serves as a precursor for the MDHDC adduct. Upon the basis of chemical analysis and NMR spectroscopy, two initial reaction steps appear to be a prerequisite for MDHDC formation. One step involves the reaction of one molecule of malondialdehyde and one of acetaldehyde with an amino group of a protein to form the FAAB product, while the other step involves the generation of a malondialdehyde-enamine. It appears that generation of the MDHDC adduct requires the FAAB moiety to be transferred to the nitrogen of the MDA-enamine. For efficient reaction of FAAB with the enamine to take place, additional experiments indicated that these two intermediates likely must be in positions on the protein of close proximity to each other. Further studies showed that the incubation of liver proteins from ethanol-fed rats with MDA resulted in a marked generation of MDHDC adducts, indicating the presence of a pool of FAAB adducts in the liver of ethanol-fed animals. Overall, these findings show that MDHDC-protein adduct formation occurs via the reaction of the FAAB moiety with a malondialdehyde-enamine, and further suggest that a similar mechanism may be operative in vivo in the liver during prolonged ethanol consumption.
Keyword Chemistry, Medicinal
Chemistry, Multidisciplinary
Oxidative Stress
Circulating Antibodies
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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Created: Tue, 14 Aug 2007, 15:36:16 EST