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 byproduct of the reaction catalyzed by NOS family (NOS; EC 1.14.13.39).[6] It is also prevalent in trichohyalin at the inner root sheath and medulla of hair follicles, where it is synthesized from arginine.[7]Arginine is first oxidized into N-hydroxyl-arginine, which is then further oxidized to citrulline concomitant with release of nitric oxide.
Citrulline is also made by enterocytes of the small intestine.[2][8]
Function
Citrulline is a metabolic intermediate within the urea cycle, which is the pathway by which mammals excrete ammonia by converting it into urea. Citrulline is also produced as a byproduct of the enzymatic production of nitric oxide from the amino acid arginine, catalyzed by nitric oxide synthase. In the yeast species Saccharomyces cerevisiae, citrulline is a metabolic intermediate in the latter, cytosolic half of the arginine biosynthesis pathway.[9]
Several proteins contain citrulline as a result of a post-translational 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 with the help of calcium ions. Proteins that normally contain citrulline residues include myelin basic protein (MBP), filaggrin, and several histone proteins, whereas other proteins, such as fibrin and vimentin are susceptible to citrullination during cell death and tissue inflammation.
Circulating citrulline concentration is a biomarker of intestinal functionality.[10][11]
^Early references spell Ryo Odake's name as Ryo Othake.
References
^"Citrulline - Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 16 September 2004. Identification. Retrieved 1 May 2012.
^Rogers, G. E.; Rothnagel, J. A. (1983). "A sensitive assay for the enzyme activity in hair follicles and epidermis that catalyses the peptidyl-arginine-citrulline post-translational modification". Current Problems in Dermatology. 11: 171–184. doi:10.1159/000408673. ISBN978-3-8055-3752-0. PMID6653155.