Citrulline

Biosynthesis

Citrulline can be derived from:

• from arginine via nitric oxide synthase, as a byproduct of the production of nitric oxide for signaling purposes
• from ornithine through the breakdown of proline or glutamine/glutamate
• from asymmetric dimethylarginine via DDAH

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). It is also prevalent in trichohyalin at the inner root sheath and medulla of hair follicles, where it is synthesized from arginine.{{Cite journal

Citrulline is also made by enterocytes of the small intestine.

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.

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.

Commercial use

L-citrulline is sold as a dietary supplement, usually in powder form. Advocates suggest that since L-citrulline boosts nitric oxide production, helping arterial function and thus blood flow throughout the body, this might be helpful in treating or preventing various ailments.

• Lowering blood pressure in people with elevated blood pressure.
• Easing symptoms of mild-to-moderate erectile dysfunction, with fewer risks than Viagra.
• Ameliorating circulatory problems such as slow wound healing due to diabetes.
• Raising muscle protein levels, preventing malnourishment in the elderly and possibly improving athletic performance.
• Treating intestinal problems, including short bowel syndrome, celiac disease and radiation-caused small bowel damage
• Various genetic disorders and health conditions such as liver disease, Parkinson's disease and certain dementias.

Some of these assertions are based on animal studies, and like most dietary supplement claims have not been endorsed by the Food and Drugs Administration.

L-citrulline is added to certain energy drinks such as Reign and touted for a claimed thermogenic effect.

References

References

1. (16 September 2004). "Citrulline - Compound Summary". National Center for Biotechnology Information.
2. Banerjee, Aryamitra. (2014-01-01). "Chapter 15 - Gastrointestinal toxicity biomarkers". Academic Press.
3. "Nos2 - Nitric Oxide Synthase". Uniprot Consortium.
4. (2000). "Lehninger principles of biochemistry". Worth Publishers.
5. DeLegge, Mark H.. (2019-01-01). "Chapter 7 - Enteral Access and Enteral Nutrition in Patients With Short Bowel Syndrome". Academic Press.
6. "Saccharomyces cerevisiae citrulline biosynthesis".
7. (2017-10-12). "Citrulline as a marker of intestinal function and absorption in clinical settings: A systematic review and meta-analysis". United European Gastroenterology Journal.
8. (2000). "Post-absorptive plasma citrulline concentration is a marker of intestinal failure in short bowel syndrome patients". Gastroenterology.
9. (2019). "Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis". Avicenna Journal of Phytomedicine.
10. "L-citrulline". WebMD LLC.
11. Label on Reign Inferno Watermelon Overlord can; Reign Beverage Company: Los Angeles, 2020