DEGENERATIVE CHEMISTRY OF MALONDIALDEHYDE - STRUCTURE, STEREOCHEMISTRY, AND KINETICS OF FORMATION OF ENAMINALS FROM REACTION WITH AMINO-ACIDS

Malondialdehyde (MDA) is a naturally occurring compound produced in biological materials as a result of polyunsaturated lipid oxidation or from irradiation of certain compounds. Malondialdehyde chemistry has long been of interest in food science and has received attention recently because of suggestions that it may play a role in cellular aging and in a host of other degenerative biological transformations associated with lipid peroxidation. The detrimental effects of MDA are believed to result from its reaction with primary amino groups of biological macromolecules. So that further insight into the specific nature of these interactions could be gained, the reaction of pure MDA with several amino acid derivatives was studied at pH 4.2. The products from the reaction were enaminals, and 1H and 13C NMR spectroscopy showed evidence of both s-cis and s-trans conformations in CDCl3 while only the s-trans form was evident in D2O. This represents the 1st detailed structural analysis of these products. The rate and equilibrium constants for enaminal formation were determined with the use of UV spectroscopy. With histidine, tyrosine, arginine and tryptophan there was no evidence for reaction of MDA at positions other than the .alpha.-amino group and the possible implications of this finding in MDA-protein interactions are discussed. The reactions of the more stable methylmalondialdehyde were examined as well.