Homocitrulline: An Analog and Confounder Related to Citrulline

A structural homolog to citrulline, homocitrulline, can be present in proteins and peptides as a product of posttranslational modification. Homocitrulline is formed nonenzymatically from lysine residues in the polypeptide chain by the action of cyanate. The latter compound is derived either from urea or, via a reaction catalyzed by the enzyme myeloperoxidase (MPO), from thiocyanate. The formation of homocitrulline is known as carbamoylation or carbamylation. In humans, this process takes place predominantly in two types of situations: uremia and inflammation. Smoking increases the circulating thiocyanate concentration and thus enhances carbamoylation of proteins.