title: Spontaneous degradation and enzymatic repair of aspartyl and asparaginyl residues in aging red cell proteins analyzed by computer simulation.
abstract: The inherent instability of proteins may be a limiting factor in the longevity of an organism. Spontaneously altered forms may themselves be toxic, or their accumulation may simply crowd out normal proteins. Two of the major sites of nonenzymatic degradation are aspartyl and asparaginyl residues, which are susceptible to an intramolecular reaction that results in the deamidation of asparaginyl residues and the isomerization and racemization of both aspartyl and asparaginyl residues. In all eucaryotic cells examined so far, an enzyme is present that can recognize at least some of these damaged sites and initiate their conversion to normal forms. This enzyme, the type II protein carboxyl methyltransferase, catalyzes the methyl esterification of L-isoaspartyl and D-aspartyl residues, enabling them to spontaneously revert to their normal L-aspartyl configurations. In this study, we utilize data on the rates of spontaneous degradation and enzymatic methylation in a computer program that simulates these reactions in the intact human erythrocyte. The results show that the methyltransferase may have an important role in limiting the accumulation of proteins containing altered aspartyl and asparaginyl residues.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles.
authors.forename: J D
authors.initials: JD
authors.lastname: Lowenson
authors.forename: S
authors.initials: S
authors.lastname: Clarke
mesh_terms: D001216:Asparagine / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004905:Erythrocyte Aging / Q000502:physiology*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008780:Methyltransferases / Q000494:pharmacology; D008954:Models, Biological
chemical_list: D001798:Blood Proteins; D006454:Hemoglobins; D001224:Aspartic Acid; D001216:Asparagine; D008780:Methyltransferases