Nonenzymatic Post-Translational Modification Derived Products: New Biomarkers of Protein Aging

During their biological life, proteins are exposed in a cumulative way to irreversible nonenzymatic post-translational modifications that are responsible for their molecular aging and generate specific by-products called post-translational modification derived products (PTMDPs). PTMDPs are involved in the pathogenesis of various diseases such as diabetes mellitus, renal insufficiency and atherosclerosis, and are potential biomarkers in clinical practice. Nonenzymatic glycation refers to the spontaneous binding of glucose and reducing sugars to free amino groups and is amplified by oxidative processes (referred to as glycoxidation ). It generates many reactive by-products such as aldehydes and leads to the formation of advanced glycation end products (AGEs). AGEs accumulate in vivo, alter tissue organization and activate membrane receptors such as RAGE, which triggers inflammatory responses. Carbamylation is due to the binding of isocyanic acid, formed in vivo either by spontaneous dissociation of urea or by action of myeloperoxidase on thiocyanate, and generates homocitrulline from lysine groups. Carbamylation leads to alteration of the structural and biological properties of proteins, and favors inflammation and atherosclerosis. PTMDPs may be assayed by different methods, among others LC-MS/MS or immuno assays, constitute a promising field of investigation in basic research and are potential major biomarkers in laboratory medicine.