carbamylation

Carbamylation is a non-enzymatic post-translational modification in which cyanate or isocyanic acid reacts with amino groups on proteins, lipids, and nucleic acids to form stable carbamoyl adducts. In biological systems, cyanate is in equilibrium with its precursor urea; increased urea levels—such as in chronic kidney disease—raise cyanate concentration and promote carbamylation. This process is distinct from enzymatic carbamoylation mediated by carbamoyl phosphate in the urea cycle.

The chemical targets are mainly the primary amino groups, including the N-terminus and the ε-amino group of lysine. These groups react with isocyanic acid to form N-carbamyl derivatives; modification of the lysine ε-amino group yields homocitrulline after rearrangement. Carbamylation alters charge, steric properties, and protein function, and can affect protein stability and interactions.

Biological relevance and disease associations have been observed. Carbamylated proteins can accumulate in chronic kidney disease and contribute to vascular stiffening and atherosclerosis. Elevated levels of homocitrulline, a biomarker of carbamylation, in plasma or tissues correlate with adverse outcomes. Carbamylation can also occur during inflammation and aging, reflecting exposure to cyanate under various conditions.

Detection and research rely on analytical techniques such as mass spectrometry to measure protein-bound homocitrulline or Nε-carbamyllysine; immunoassays exist but vary in specificity. Because carbamylation is largely irreversible, cellular repair is limited. Prevention focuses on reducing cyanate exposure or urea levels, for example via dialysis in chronic kidney disease or management of inflammation. Ongoing work investigates the pathophysiological roles and potential therapeutic strategies to mitigate harmful effects.