Conversion of lysine to N-epsilon-(carboxymethyl)lysine increases susceptibility of proteins to metal-catalyzed oxidation

Metal-catalyzed oxidation (MCO) of proteins leads to the conversion of some amino acid residues to carbonyl derivatives, and may result in loss of pro tein function. It is well documented that reactions with oxidation products of sugars, lipids, and amino acids can lead to the conversion of some lysi ne residues of proteins to N-epsilon-(carboxymethyl)lysine (CML) derivative s, and that this increases their metal binding capacity. Because post-trans lational modifications that enhance their metal binding capacity should als o increase their susceptibility to MCO, we have investigated the effect of lysine carboxymethylation on the oxidation of bovine serum albumin (BSA) by the Fe3+/ascorbate system. Introduction of similar to 10 or more mol CML/m ol BSA led to increased formation of carbonyls and of the specific oxidatio n products glutamic and adipic semialdehydes. These results support the vie w that the generation of CML derivatives on proteins may contribute to the oxidative damage that is associated with aging and a number of age-related diseases. (C) 1999 Academic Press.