The chemical conversion of arginine to citrulline, known as citrullination or deimination.
Citrullination or deimination is the conversion of the amino acid arginine in a protein into the amino acid citrulline. 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.
Enzymes called arginine deiminases (ADIs) catalyze the deimination of free arginine, while protein arginine deiminases or peptidylarginine deiminases (PADs) replace the primary ketimine group (>C=NH) by a ketone group (>C=O). Arginine is positively charged at a neutral pH, whereas citrulline has no net charge. This increases the hydrophobicity of the protein, which can lead to changes in protein folding, affecting the structure and function.
The immune system can attack citrullinated proteins, leading to autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS). 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, about as sensitive as rheumatoid factor (70–78%) for diagnosis of RA, and are detectable from even before the onset of clinical disease.[1]
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.[2] An ELISA system utilises genetically modified citrullinated vimentin (MCV), a naturally occurring isoform of vimentin to improve the performance of the test.[3]
In the reaction from arginine to citrulline, one of the terminal nitrogen atoms of the arginine side chain is replaced by an oxygen. Thus, arginine's positive charge (at physiological pH) is removed, altering the protein's tertiary structure. The reaction uses one water molecule and yields ammonia as a side-product:
^Coenen D, Verschueren P, Westhovens R, Bossuyt X (March 2007). "Technical and diagnostic performance of 6 assays for the measurement of citrullinated protein/peptide antibodies in the diagnosis of rheumatoid arthritis". Clinical Chemistry. 53 (3): 498–504. doi:10.1373/clinchem.2006.078063. PMID 17259232.
^Nicaise Roland P, Grootenboer Mignot S, Bruns A, et al. (2008). "Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy". Arthritis Research & Therapy. 10 (6): R142. doi:10.1186/ar2570. PMC 2656247. PMID 19077182.
^Soós L, Szekanecz Z, Szabó Z, et al. (August 2007). "Clinical evaluation of anti-mutated citrullinated vimentin by ELISA in rheumatoid arthritis". The Journal of Rheumatology. 34 (8): 1658–63. PMID 17611988. Archived from the original on 2008-02-20. Retrieved 2009-10-07.
Citrullination or deimination is the conversion of the amino acid arginine in a protein into the amino acid citrulline. Citrulline is not one of the 20...
(PADs), which convert arginine into citrulline in a process called citrullination or deimination with the help of calcium ions. Proteins that normally...
in their globular domains. Such modifications include methylation, citrullination, acetylation, phosphorylation, SUMOylation, ubiquitination, and ADP-ribosylation...
protein, which include phosphorylation, methylation, deamidation, and citrullination. These forms differ by the presence or the absence of short (10 to 20...
form citrulline, in a post-translational modification process called citrullination.This is important in fetal development, is part of the normal immune...
contains the enzyme peptidyl-arginine deiminase, which is involved in citrullination. Patients with rheumatoid arthritis have increased incidence of periodontal...
associated with periodontitis are implicated as mediators of protein citrullination in the gums of people with RA. Vitamin D deficiency is more common in...
methylation, ubiquitylation, phosphorylation, sumoylation, ribosylation and citrullination. Acetylation is the most highly studied of these modifications. For...
disease rheumatoid arthritis due to its ability to stimulate protein citrullination, a post-translational protein modification targeted by autoantibodies...
symptoms often are lacking but when medical therapy is most effective. Citrullination is a modification of proteins where a nitrogen in the amino acid arginine...
(such as methylation, acetylation, ADP-ribosylation, ubiquitination, citrullination, SUMO-ylation and phosphorylation) to histone tails alter chromatin...
incidence and severity of rheumatoid arthritis. This may relate to abnormal citrullination of proteins, since the effects of smoking correlate with the presence...
reactive oxygen species (ROS) intermediaries. PAD4 is responsible for the citrullination of histones in the neutrophil, resulting in decondensation of chromatin...
responsible for the conversion of arginine to citrulline residues (citrullination). This gene may play a role in granulocyte and macrophage development...
citrulline: development of a phenylglyoxal-based probe to visualize protein citrullination". J Am Chem Soc. 134 (41): 17015–8. doi:10.1021/ja308871v. PMC 3572846...
Citrullinated protein may refer to: Any protein having undergone citrullination The proteins (often cyclic ones) being the targets of anti-citrullinated...
histone H3 citrullination contributes to demyelination, research demonstrates that inhibitors of the enzymes involved in this citrullination improve the...
It renders modifications of protein termini, such as acetylation and citrullination, easily accessible and searchable and provides the means to identify...
Spectrometry-Based Method for Simultaneous Qualitative and Quantitative Protein Citrullination Analysis of Complex Biological Samples (2020) US 20210181206 A1 Phillips...
Genomic and Precision Medicine Distinguished Achievement Award Role of citrullination in diagnosing diseases (2021) US 11,105,817 B2 Biomarkers of myocardial...
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