What is "citrullination"

n. (context biochemistry English) The posttranslational modification of the amino acid arginine in a protein into the amino acid citrulline

__FORCETOC__ Citrullination or deimination is the conversion of the amino acid arginine in a protein into the amino acid citrulline. Enzymes called peptidylarginine deiminases (PADs) replace the primary ketimine group (=NH) by a ketone group (=O).

Citrullination controls the expression of genes, particularly in the developing embryo. The immune system often attacks citrullinated proteins, leading to autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.

Citrulline is not one of the 20 standard amino acids encoded by DNA in the genetic code. Instead, it is the result of a post-translational modification.

Citrullination 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.

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. Therefore, citrullination can change the structure and function of proteins.

Proteins that normally contain citrulline residues include myelin basic protein (MBP), filaggrin, 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 may be an autoantigen in RA and other autoimmune diseases, and is used to study RA. Moreover, antibodies against mutated citrullinated vimentin (MCV) may be useful for monitoring effects of RA therapy. An 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 side chain is replaced by an oxygen. The reaction uses one water molecule and yields ammonia as a side-product: