The chemistry of Maillard or browning reactions of glycated proteins is being studied in model systems in vitro in order to characterize potential reaction pathways and products in biological systems. In previous work with the Amadori rearrangement product N alpha-formyl-N epsilon-fructoselysine (fFL), an analog of glycated lysine residues in proteins, we showed that fFL was oxidatively cleaved between C-2 and C-3 of the carbohydrate chain to yield N epsilon-carboxymethyllysine (CML) and D-erythronic acid. We then detected CML in proteins glycated in vitro, as well as in human lens proteins and collagen in vivo (Ahmed, M. U., Thorpe, S. R., and Baynes, J. W. (1986) J. Biol. Chem. 261, 4889-4894). This work provided an explanation for the origin of CML in human urine and evidence for non-browning pathways of the Maillard reaction in vivo. In this report we describe the identification of a second set of products resulting from oxidative cleavage of fFL between C-3 and C-4 of the sugar chain, i.e. 3-(N epsilon-lysino)-lactic acid (LL) and D-glyceric acid. The formation of LL from fFL was increased at slightly acid pH, representing about 30% of the yield of CML at pH 6.4, compared with 4% at pH 7.4 in phosphate buffer. By gas chromatography-mass spectroscopy, LL was detected in proteins glycated in vitro and then identified as a natural product in human lens proteins and urine. Our results indicate that oxidative degradation of Amadori adducts toproteins occurs in vivo, leading to formation and excretion of CML and LL. These non-browning pathways for reaction of Amadori compounds may be physiologically relevant mechanisms for averting potentially damaging consequences of the Maillard reaction.
Published in Journal of Biological Chemistry, Volume 263, Issue 18, 1988, pages 8816-8821.
This research was originally published in the Journal of Biological Chemistry. Ahmed MU, Dunn JA, Walla MD, Thorpe SR, Baynes JW. Oxidative Degradation of Glucose Adducts to Protein: Formation of 3-(Ne-Lysino)-Lactic Acid from Model Compounds and Glycated Proteins. Journal of Biological Chemistry. 1988; 263:8816-8821. © the American Society for Biochemistry and Molecular Biology.