homocitrulline

Homocitrulline, also called N6-carbamyl-lysine, is a non-proteinogenic amino acid derivative that arises when the amino group of lysine residues is carbamylated by cyanate. In biological samples it may be found both as a free amino acid and as part of carbamylated proteins.

Carbamylation is a non-enzymatic post-translational modification that occurs when cyanate, derived from urea breakdown, reacts with exposed lysine side chains. This reaction can accumulate under conditions of increased urea in the blood, such as chronic kidney disease and other inflammatory states, and contributes to altered protein function.

Because protein carbamylation accumulates in patients with kidney disease and related metabolic disturbances, homocitrulline levels in plasma or urine are used as a biomarker of carbamylation and uremic stress. Elevated levels have been associated with cardiovascular risk and adverse outcomes in some studies, though its clinical utility is still under investigation.

Homocitrulline is chemically distinct from citrulline, a product of arginine deimination (citrullination). It reflects a different modification pathway (carbamylation) and has separate implications for protein chemistry and disease.

Analytical measurement of homocitrulline typically relies on mass spectrometry methods, such as LC-MS/MS, after appropriate sample preparation. Interpretation requires consideration of kidney function, inflammation, and overall urea burden.