Citrullination Biology — SCE Rheumatology MCQ
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Correct answer: B — Calcium-dependent PAD-mediated deimination of peptidyl arginine, generating neutral peptidyl citrulline
Explanation lettering: C = shown as A · D = shown as B · A = shown as C · E = shown as D · B = shown as E
Citrullination is a post-translational, calcium-dependent deimination reaction catalysed by peptidylarginine deiminase (PAD) enzymes. PADs act on arginine already incorporated into proteins, converting its positively charged guanidinium group into the neutral ureido group of citrulline. This can alter protein structure and create epitopes recognised by anti-citrullinated protein antibodies, which anti-CCP assays detect. Carbamylation (A) converts lysine to homocitrulline and can generate separate autoantigens in rheumatoid arthritis, but it is not citrullination. Transglutaminase-mediated glutamine deamidation (B) is a distinct modification classically relevant to coeliac disease. Free arginine is not modified before translation by PADs (C), and arginase acts on free arginine in nitrogen metabolism rather than generating citrullinated protein epitopes (E).
Reference: Kijak-Boćkowska M, Czerwińska J, Owczarczyk-Saczonek A. Peptidylarginine Deiminases: An Overview of Recent Advances in Citrullination Research. International Journal of Molecular Sciences. 2025;26:12060. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12732937/