Citrullination: Difference between revisions

Latest revision as of 11:04, 15 February 2025

Citrullination[edit]

Diagram illustrating the process of citrullination.

Citrullination, also known as deimination, is a post-translational modification of proteins where the amino acid arginine is converted into citrulline. This process is catalyzed by a family of enzymes known as peptidylarginine deiminases (PADs). Citrullination plays a significant role in various physiological processes and is implicated in several diseases.

Mechanism[edit]

Citrullination involves the conversion of the positively charged guanidinium group of arginine into a neutral urea group, resulting in the formation of citrulline. This modification can alter the structure and function of proteins, affecting their interaction with other molecules and their stability.

Biological Significance[edit]

Citrullination is involved in the regulation of gene expression, the formation of neutrophil extracellular traps (NETs), and the modulation of the immune response. It is crucial in the development and function of the central nervous system and the skin.

Role in Disease[edit]

Citrullination is associated with several autoimmune diseases, most notably rheumatoid arthritis (RA). In RA, the immune system produces autoantibodies against citrullinated proteins, known as anti-citrullinated protein antibodies (ACPAs), which are used as a diagnostic marker for the disease.

Enzymes Involved[edit]

The conversion of arginine to citrulline is catalyzed by the peptidylarginine deiminase (PAD) family of enzymes. There are five known PAD isozymes in humans: PAD1, PAD2, PAD3, PAD4, and PAD6, each with distinct tissue distributions and substrate specificities.

Clinical Implications[edit]

The detection of citrullinated proteins and ACPAs is important in the diagnosis and management of rheumatoid arthritis. Research is ongoing to understand the role of citrullination in other diseases, such as multiple sclerosis, Alzheimer's disease, and certain types of cancer.

Related Pages[edit]

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-'''Citrullination''' is a post-translational modification of [[proteins]] where the amino acid [[arginine]] is converted into citrulline by the enzyme family known as [[peptidylarginine deiminases]] (PADs). This process involves the hydrolysis of arginine into citrulline, resulting in a change in the protein's structure and function. Citrullination plays a crucial role in various physiological and pathological processes, including [[cell death]], [[gene expression]], and the development of autoimmune diseases such as [[rheumatoid arthritis]] (RA).
+== Citrullination ==
-==Process==
+[[File:citrullination.svg|thumb|right|Diagram illustrating the process of citrullination.]]
-The citrullination process is catalyzed by the PAD enzymes, which are calcium-dependent. There are five known PAD isozymes in humans, PAD1, PAD2, PAD3, PAD4, and PAD6, each with distinct tissue distributions and substrate specificities. The conversion of arginine to citrulline involves the deimination of the guanidino group of arginine, resulting in the production of citrulline and ammonia. This modification can affect the protein's charge, conformation, and the ability to form [[hydrogen bonds]], thereby altering its function and interactions with other molecules.
-==Biological Significance==
+'''Citrullination''', also known as '''deimination''', is a post-translational modification of proteins where the amino acid [[arginine]] is converted into [[citrulline]]. This process is catalyzed by a family of enzymes known as [[peptidylarginine deiminases]] (PADs). Citrullination plays a significant role in various physiological processes and is implicated in several diseases.
-Citrullination has been implicated in various biological processes. In the skin, it is involved in the formation of the epidermal barrier. In the brain, it can affect [[myelin]] basic protein function, which is significant in the context of [[multiple sclerosis]]. In the immune system, citrullination alters the structure of [[histones]], affecting [[gene expression]] and promoting [[inflammation]].
-==Pathological Significance==
+== Mechanism ==
-The pathological significance of citrullination is most notably observed in rheumatoid arthritis, where citrullinated proteins are targeted by autoantibodies known as anti-citrullinated protein antibodies (ACPAs). The presence of ACPAs is a hallmark of RA and is used in the diagnosis of the disease. Citrullination is also associated with other autoimmune diseases, including [[multiple sclerosis]], [[Alzheimer's disease]], and [[cancer]], suggesting a broad impact on human health.
-==Detection and Clinical Relevance==
+Citrullination involves the conversion of the positively charged guanidinium group of arginine into a neutral urea group, resulting in the formation of citrulline. This modification can alter the structure and function of proteins, affecting their interaction with other molecules and their stability.
-The detection of citrullinated proteins and ACPAs is crucial for the diagnosis and management of diseases like RA. Various assays, including the anti-cyclic citrullinated peptide (anti-CCP) test, are used clinically to detect ACPAs. The presence of these antibodies often precedes the clinical onset of RA, making them valuable predictive markers.
-==Conclusion==
+== Biological Significance ==
-Citrullination is a significant post-translational modification with wide-ranging effects on protein function and disease. Understanding the role of citrullination and PAD enzymes in health and disease can provide insights into the mechanisms of autoimmune diseases and lead to the development of novel therapeutic strategies.
+Citrullination is involved in the regulation of gene expression, the formation of [[neutrophil extracellular traps]] (NETs), and the modulation of the [[immune response]]. It is crucial in the development and function of the [[central nervous system]] and the [[skin]].
+=== Role in Disease ===
+Citrullination is associated with several autoimmune diseases, most notably [[rheumatoid arthritis]] (RA). In RA, the immune system produces [[autoantibodies]] against citrullinated proteins, known as [[anti-citrullinated protein antibodies]] (ACPAs), which are used as a diagnostic marker for the disease.
+== Enzymes Involved ==
+The conversion of arginine to citrulline is catalyzed by the peptidylarginine deiminase (PAD) family of enzymes. There are five known PAD isozymes in humans: PAD1, PAD2, PAD3, PAD4, and PAD6, each with distinct tissue distributions and substrate specificities.
+== Clinical Implications ==
+The detection of citrullinated proteins and ACPAs is important in the diagnosis and management of rheumatoid arthritis. Research is ongoing to understand the role of citrullination in other diseases, such as [[multiple sclerosis]], [[Alzheimer's disease]], and certain types of [[cancer]].
+== Related Pages ==
+* [[Post-translational modification]]
+* [[Autoimmune disease]]
+* [[Rheumatoid arthritis]]
+* [[Peptidylarginine deiminase]]
-[[Category:Biochemistry]]
 [[Category:Post-translational modification]]
 [[Category:Immunology]]
-{{biochemistry-stub}}
+[[Category:Enzymes]]