L-citrulline, reduces muscle fatigue

The organic compound citrulline is an α-amino acid. Its name is derived from citrullus, theLatin word for watermelon, from which it was first isolated in 1914 by Koga & Odake. It was finally identified by Wada in 1930.^[2] It has the idealized formulaH₂NC(O)NH(CH₂)₃CH(NH₂)CO₂H. It is a key intermediate in the urea cycle, the pathway by which mammals excrete ammonia.

Although human DNA does not code for citrulline directly, several proteins contain citrulline as a result of a posttranslational modification. These citrulline residues are generated by a family of enzymes called peptidylarginine deiminases (PADs), which convert arginine into citrulline in a process called citrullination or deimination. Proteins that normally contain citrulline residues include myelin basic protein (MBP), filaggrin, and several histoneproteins, whereas other proteins, such as fibrin and vimentin are susceptible to citrullination during cell death and tissue inflammation.Citrulline is made from ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle. It is also produced from arginine as a by-product of the reaction catalyzed by NOS family (NOS; EC 1.14.13.39).^[3] It is made from arginine by the enzymetrichohyalin at the inner root sheath and medulla of hair follicles.^[4] Arginine is first oxidized into N-hydroxyl-arginine, which is then further oxidized to citrulline concomitant with release of nitric oxide.

Patients with rheumatoid arthritis often have detectable antibodies against proteins containing citrulline. Although the origin of this immune response is not known, detection of antibodies reactive with citrulline (anti-citrullinated protein antibodies) containing proteins or peptides is now becoming an important help in the diagnosis of rheumatoid arthritis.^[5]

In recent studies, citrulline has been found to relax blood vessels.^[6] Circulating citrulline concentration is, in humans, a biomarker of intestinal functionality.^[7]

Citrulline in the form of citrulline malate is sold as a performance-enhancing athletic dietary supplement, which was shown to reduce muscle fatigue in a preliminary clinical trial.^[8]

The rind of watermelon (Citrullus lanatus) is a good natural source of citrulline.^[9]