[Carbamylation of proteins--mechanism, causes and consequences]

Abstract

Carbamylation (carbamoylation) is a post-translational modification resulting from the nonenzymatic reaction between isocyanic acid and free functional groups of proteins, in particular with the free amino groups. This reaction alters structural and functional properties of proteins and results in faster aging of proteins. Urea present in the body can be transformed into cyanate and its more reactive form, isocyanic acid. High concentration of urea is associated with some diseases, especially with chronic renal failure and atherosclerosis. In human tissues, urea and cyanate are in equilibrium in aqueous solutions. Surprisingly, concentration of isocyanate in the body is much lower than it would appear from the kinetic parameters of urea decomposition. The low concentration of isocyanic acid results from its high reactivity and short half-life. In this review we describe the biochemical mechanism of carbamylation of proteins and free amino acids. We summarize the literature data for carbamylation of hemoglobin, lipoproteins, albumin, membrane proteins and erythropoietin in chronic renal failure. In summary, the carbamylation of proteins may have a negative impact on their biological activity and may contribute to the deterioration of patients with chronic renal failure.