The organic compound citrulline
is an α-amino acid
. Its name is derived from citrullus
, the Latin
word for watermelon
, from which it was first isolated in 1930.
It has the idealized formula
H. It is a key intermediate in the urea cycle
, the pathway by which mammals excrete ammonia
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 18.104.22.168). Arginine is first oxidized into N-hydroxyl-arginine, which is then further oxidized to citrulline concomitant with release of nitric oxide.
Although citrulline is not coded for by DNA
directly, several proteins are known to 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
, and several histone
proteins, whereas other proteins, such as fibrin
are susceptible to citrullination during cell death and tissue inflammation
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.
In recent studies, citrulline has been found to relax blood vessels.
Citrulline in the form of citrulline malate
is sold as a performance-enhancing athletic dietary supplement
which is said to reduce muscle fatigue.
The rind of watermelon (Citrullus lanatus) is a good natural source of citrulline.