title: Does the chemical instability of aspartyl and asparaginyl residues in proteins contribute to erythrocyte aging? The role of protein carboxyl methylation reactions.
abstract: As erythrocytes age in the circulation, their proteins are subjected to a wide variety of spontaneous reactions that lead to the formation of covalent derivatives. In this article, we concentrate on nonenzymatic reactions at aspartyl and asparaginyl residues, both of which are especially vulnerable targets on the protein. These residues can be altered by a combination of deamidation, isomerization, and racemization reactions that form D- and L-aspartyl and D- and L-isoaspartyl residues. We present evidence that two of these modified residues are targets for an enzymatic methyl esterification reaction, and that methylation may represent the means by which cells respond to this type of protein damage. The metabolic fate of the methyl ester is unclear, but in vitro model studies with peptides and proteins suggest that this methylation can lead to the partial repair of the altered protein and can mitigate the loss of protein function.
mesh_terms: D001216:Asparagine / Q000378:metabolism*; D001224:Aspartic Acid / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D004905:Erythrocyte Aging; D006801:Humans; D008745:Methylation
chemical_list: D001798:Blood Proteins; D001224:Aspartic Acid; D001216:Asparagine