Methylglyoxal (MGO) is generated as a by-product of glycolysis (~0.1% - 0.4% of the total glycolytic flux). Under physiologic conditions, MGO is detoxified by the glyoxalase system, which is comprised of two enzymes (glyoxalase 1, GLO1, and GLO2). When this system is compromised (e.g. diabetes), concentrations of MGO are elevated and it can adduct proteins and DNA, yielding stable, long-lived adducts on Lys, Arg, and deoxyguanosine. As a result, systems are in place to remove these potentially damaging modifications. We have shown that the deglycase, DJ-1 , is capable of removing the intermediate aminocarbinol adduct, yielding the unmodified Arg and lactate. We are interested in fully understanding these enzymatic reactions and elucidating the consequences of protein adduction when these detoxification mechanisms are compromised. Enzymatic reactions are shown in green.