Protein Carbamylation: Chemistry, Pathophysiological Involvement, and Biomarkers

Abstract

Protein carbamylation refers to a nonenzymatic modification, which consists in the binding of isocyanic acid on protein functional groups. This reaction is responsible for the alteration in structural and functional properties of proteins, which participate in their molecular aging. Protein molecular aging is now considered a molecular substratum for the development of chronic and inflammatory diseases, including atherosclerosis, chronic kidney disease, or rheumatoid arthritis. As a consequence, carbamylation-derived products have been proposed as interesting biomarkers in various pathological contexts and appropriate analytical methods have been developed for their quantification in biological fluids. The purpose of this review is (i) to describe the biochemical bases of the carbamylation reaction, (ii) to explain how it contributes to protein molecular aging, (iii) to provide evidence of its involvement in aging and chronic diseases, and (iv) to list the available biomarkers of carbamylation process and the related analytical methods.

Keywords: Atherosclerosis; Biomarkers; Carbamylation; Chronic kidney disease; Homocitrulline; Isocyanic acid; Protein molecular aging; Rheumatoid arthritis.