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Citrullination or deimination is the term used for the post-translational modification of the amino acid arginine in a protein into the amino acid citrulline. This reaction, shown below, is performed by enzymes called peptidylarginine deiminases (PADs). Note that citrullination of proteins is distinct from the formation of the free amino acid citrulline as part of the urea cycle or as a byproduct of enzymes of the nitric oxide synthase family.
The conversion of arginine into citrulline can have important consequences for the structure and function of proteins, since arginine is positively charged at a neutral pH, whereas citrulline is uncharged. This increases the hydrophobicity of the protein, leading to changes in protein folding.
Proteins that normally contain citrulline residues include MBP, fillagrin and several histone proteins, while other proteins, like fibrin and vimentin can get citrullinated during cell-death and tissue inflammation. Fibrin and fibrinogen may be favored sites for arginine deimination within rheumatoid joints. Test for presence of anti-citrullinated protein (ACP) antibodies are highly specific (88-96%) for rheumatoid arthritis (RA), about as sensitive as Rheumatoid factor (70-78%) for diagnosis of RA, and are detectable from even before the onset of clinical disease.
Citrullinated vimentin is a very promising autoantigen in RA, and more importantly a very suitable tool for studying this systemic autoimmune disease. Moreover, anti-MCV antibodies may be useful for monitoring effects of RA therapy. A newly developed ELISA system utilises genetically modified citrullinated vimentin (MCV), a naturally occurring isoform of vimentin to improve the performance of the test.
In the reaction from arginine to citrulline, one of the terminal nitrogen atoms of the arginine sidechain is replaced by an oxygen. The reaction uses one water molecule and yields ammonia as a side product:
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