Citrullination

Citrullination

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

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

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