Cellular proteins susceptible to carbamoylation

Cellular proteins susceptible to carbamoylation represent a heterogeneous group of proteins that undergo non-enzymatic post-translational modification (PTM) by isocyanic acid. This chemical modification primarily targets the N-terminal amino groups and the epsilon-amino groups of lysine residues, transforming them into homocitrulline (Jaisson et al., 2011, Journal of Proteomics). Carbamoylation is driven by two main pathways: the spontaneous dissociation of urea, which is prevalent in chronic kidney disease (CKD), and the oxidation of thiocyanate by myeloperoxidase (MPO) during inflammation and smoking (Wang et al., 2007, Nature Medicine). These modifications lead to structural changes, loss of enzymatic activity, and increased immunogenicity, contributing to the pathogenesis of atherosclerosis, renal failure, and rheumatoid arthritis (Verbrugge et al., 2015, Journal of the American College of Cardiology). While not a single molecular target, the carbamoylation process and its products are significant in drug development as biomarkers of uremic stress and as targets for therapeutic intervention using cyanate scavengers or MPO inhibitors (Gillery & Jaisson, 2014, Clinical Chemistry and Laboratory Medicine).

Other names

Carbamoylated proteinsCarbamylated proteinsHomocitrulline-containing proteinsIsocyanic acid-modified proteins

The primary mechanism involves the competitive scavenging of isocyanic acid by nucleophilic agents such as amino acids or the reduction of isocyanic acid production by inhibiting myeloperoxidase or lowering systemic urea levels (Gillery & Jaisson, 2014, Clinical Chemistry and Laboratory Medicine).