Citrulline is a non-essential α-amino acid, isolated and identified in 1914 by two Japanese researchers, Yotaro Koga and Ryo Odake, from the juice of the watermelon, Citrullus vulgaris, is synthesised almost exclusively by the intestine and is released by enterocytes. The bioavailability of citrulline depends on intestinal absorption and amino acid transport systems.

Citrulline is metabolised into L-arginine when administered orally In commercial products, particularly cosmetics, L-Citrulline, an intermediate in the urea cycle, is usually found instead of Citrulline. It belongs to the amino acid family L-glutamate and is produced by microbial fermentation using mainly Corynebacterium glutamicum.

Industrially it is in the form of a white powder. It is obtained by the reaction of L-arginine hydrochloride with sodium hydroxide, copper oxide and hydrogen sulphide. 

What it is used for and where

Medical

Citrulline supplementation may be useful in all those circumstances where arginine would be indicated, but in cases where arginine would be considered harmful. L-citrulline supplementation is considered a better alternative to L-arginine supplementation in a wide variety of diseases caused by L-arginine deficiency (1). Its use has been investigated in cases of malnutrition associated with intestinal insufficiency, ageing and sarcopenia (clinical studies found that muscle mass and motor activity were increased when malnourished elderly mice were re-fed), cardiovascular disease (improved cardiac performance with exercise and sense of well-being and reduced total leukocytes and neutrophils) (2).

Other clinical studies have shown the positive effect of citrulline, which significantly reduced post-exercise assessment of perceived exertion and post-exercise muscle pain itself without affecting blood lactate levels (3).

L-citrulline is considered a biomarker for monitoring intestinal integrity (4).

Cosmetics

L-citrulline is a protein constituent and maintains the urea cycle by alleviating skin injuries.

Other uses

Biochemical reagent.

Typical commercial product characteristicsL-citrulline

Citrulline studies

Appearance	White powder
Boiling Point	386.7±42.0°C at 760 mmHg
Melting Point	214°C
Flash Point	187.7±27.9°C
Density	1.3±0.1 g/cm3
pH	6.1~6.7
Chloride	≤0.02%
Iron	≤10ppm
Sulfate	≤0.02%
Ammonium	≤0.02%
Lead	≤10ppm
Loss on drying	≤0.20%
Residue on ignition	≤0.10%
Specific rotation	+24.5°~+26.5°
Vapor Pressure	0.0±1.9 mmHg at 25°C
Refraction Index	1.531
Water Solubility	200 g/L (20 ºC)
PSA	118.44000
LogP	-1.53
Safety

• Molecular Formula   C₆H₁₃N₃O₃
• Molecular Weight    175.19
• Exact Mass    175.095688
• CAS  372-75-8
• UNII    29VT07BGDA
• EC Number   206-759-6
• DSSTox Substance ID  
• IUPAC  (2S)-2-amino-5-(carbamoylamino)pentanoic acid
• InChI=1S/C6H13N3O3/c7-4(5(10)11)2-1-3-9-6(8)12/h4H,1-3,7H2,(H,10,11)(H3,8,9,12)/t4-/m0/s1
• InChl Key      RHGKLRLOHDJJDR-BYPYZUCNSA-N
• SMILES   C(CC(C(=O)O)N)CNC(=O)N
• MDL number  MFCD00064397
• PubChem Substance ID    329749391
• NACRES NA.24
• Beilstein    1725416
• ChEBI   16349
• RXCUI    2567  
• NCI   C53406
• RTECS    GE8803000

Synonyms

• L-(+)-Citrulline
• (2S)-2-amino-5-(carbamoylamino)pentanoic acid
• α-amino-δ-ureidovaleric acid
• N-[Hydroxy(imino)methyl]-L-ornithine

References_____________________________________________________________________

(1) Rashid J, Kumar SS, Job KM, Liu X, Fike CD, Sherwin CMT. Therapeutic Potential of Citrulline as an Arginine Supplement: A Clinical Pharmacology Review. Paediatr Drugs. 2020 Jun;22(3):279-293. doi: 10.1007/s40272-020-00384-5. PMID: 32140997; 

(2) Bahri S, Zerrouk N, Aussel C, Moinard C, Crenn P, Curis E, Chaumeil JC, Cynober L, Sfar S. Citrulline: from metabolism to therapeutic use. Nutrition. 2013 Mar;29(3):479-84. doi: 10.1016/j.nut.2012.07.002.

(3) Rhim HC, Kim SJ, Park J, Jang KM. Effect of citrulline on post-exercise rating of perceived exertion, muscle soreness, and blood lactate levels: A systematic review and meta-analysis. J Sport Health Sci. 2020 Dec;9(6):553-561. doi: 10.1016/j.jshs.2020.02.003.

(4) Maric S, Restin T, Muff JL, Camargo SM, Guglielmetti LC, Holland-Cunz SG, Crenn P, Vuille-Dit-Bille RN. Citrulline, Biomarker of Enterocyte Functional Mass and Dietary Supplement. Metabolism, Transport, and Current Evidence for Clinical Use. Nutrients. 2021 Aug 15;13(8):2794. doi: 10.3390/nu13082794.