L-Homocitrulline

Homocitrulline is an amino acid and a product of carbamylation, a post-translational modification of proteins and amino acids.^1,2 It is formed by the adduction of isocyanic acid, a product of urea degradation or thiocyanate oxidation induced by myeloperoxidase (MPO), to the ε-amino group of lysine residues.² Protein-bound homocitrulline levels are increased in the aortas of transgenic Ldlr^-/- mice expressing human MPO fed a high-fat atherogenic diet.³ Intra-articular injection of homocitrulline-containing peptides induce the development of arthritis in mice.⁴ Homocitrulline-containing peptide and anti-homocitrulline antibody levels are increased in whole blood from patients with erosive rheumatoid arthritis compared to patients with non-erosive rheumatoid arthritis.

1.Shi, J., Knevel, R., Suwannalai, P., et al.Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damageProc. Natl. Acad. Sci. USA108(42)17372-17377(2011) 2.Verbrugge, F.H., Tang, W.H.W., and Hazen, S.L.Protein carbamylation and cardiovascular diseaseKidney Int.88(3)474-478(2015) 3.Wang, Z., Nicholls, S.J., Rodriquez, E.R., et al.Protein carbamylation links inflammation, smoking, uremia and atherogenesisNat. Med.13(1)1176-1184(2007) 4.Mydel, P., Wang, Z., Brisslert, M., et al.Carbamylation-dependent activation of T cells: A novel mechanism in the pathogenesis of autoimmune arthritisJ. Immunol.184(12)6882-6890(2010)