L-citrulline is an amino acid that is produced from l-arginine through the arginine-citrulline pathway, ornithine in the degradation of proline, glutamine, and glutamate. As dimethylarginine (ADMA) is broken down, L-citrulline is also produced. This process is aided by dimethylarginine dimethylaminohydrolase (DDAH), which also produces DMA as a byproduct[1]. L-

Toxicity Summary
L-citrulline is converted to L-arginine by arginine succinate synthase. L-arginine is key to the therapeutic effects of citrulline. Many activities of L-arginine, including its potential anti-atherosclerotic effects, may be related to its role as a precursor to nitric oxide (NO). NO is produced by all tissues in the body and plays a vital role in the cardiovascular, immune, and nervous systems. NO is generated from L-arginine by NO synthase (NOS), primarily mediated by 3',5'-cyclic guanosine monophosphate (cGMP). NO activates guanylate cyclase, which catalyzes the synthesis of cGMP from guanosine triphosphate (GTP). cGMP is then converted to guanosine monophosphate by cGMP phosphodiesterase. Nitric oxide synthase (NOS) is a heme-containing enzyme with a partial sequence similar to cytochrome P-450 reductase. NOS exists in multiple isoenzymes, two of which are constitutively expressed, and one is induced by immune stimulation. Constitutive NOS present in vascular endothelial cells is called eNOS, while constitutive NOS present in the brain, spinal cord, and peripheral nervous system is called nNOS. NOS induced by immune or inflammatory stimuli is called iNOS. iNOS can be constitutively expressed in certain tissues, such as lung epithelial cells. All nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O₂) as cosubstrates, with cofactors including FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin, and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin levels. eNOS and nNOS synthesize NO in response to elevated calcium ion concentrations, or under certain conditions under non-calcium-dependent stimuli (e.g., shear stress). In vitro studies have shown that the Km value of NOS for L-arginine is in the micromolar range. The concentrations of L-arginine in endothelial cells and other cells, as well as in plasma, are in the millimolecular range. This means that under physiological conditions, NOS and its substrate L-arginine are saturated. In other words, L-arginine is not expected to be the rate-limiting step of this enzyme, and oral supplementation of this amino acid may lead to excessively high L-arginine concentrations, but this does not appear to have any effect on NO production. The reaction appears to have reached its maximum activity. However, in vivo studies have shown that under certain conditions, such as hypercholesterolemia, L-arginine can enhance endothelium-dependent vasodilation and NO production.

[1]. Quantitative Analysis of l-Arginine, Dimethylated Arginine Derivatives, l-Citrulline, and Dimethylamine in Human Serum Using Liquid Chromatography-Mass Spectrometric Method. Chromatographia. 2018;81(6):911-921.

Pharmacodynamics
Citrulline is a non-essential amino acid and a precursor to arginine. It is claimed that citrulline supplementation can increase energy levels, stimulate the immune system, and help clear ammonia (a cytotoxin). L-Citrine is produced from L-ornithine and carbamoyl phosphate in one of the core reactions of the urea cycle. It is also a byproduct of the reaction produced from L-arginine in a NO synthase-catalyzed reaction. Although L-citrulline is an amino acid, it is not involved in protein synthesis and is not one of the amino acids encoded by DNA. While citrulline cannot be integrated into proteins during protein synthesis, some proteins are known to contain citrulline as an amino acid. These citrulline residues are produced by a class of enzymes called peptidyl arginine deiminases (PADs), which convert the amino acid arginine to citrulline. Proteins containing citrulline residues include myelin basic protein (MBP), filaggrin, and several histones.

C6H13N3O3

175.188

175.095

372-75-8

9750

White to off-white solid powder

1.3±0.1 g/cm3

386.7±42.0 °C at 760 mmHg

214 °C

187.7±27.9 °C

0.0±1.9 mmHg at 25°C

1.531

-1.53

4

4

5

12

171

1

C(C[C@@H](C(=O)O)N)CNC(=O)N

RHGKLRLOHDJJDR-BYPYZUCNSA-N

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

(2S)-2-amino-5-(carbamoylamino)pentanoic acid

L-Cytrulline; L-Citrulline; Citrulline

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ≥ 50 mg/mL (~285.40 mM)

Solubility in Formulation 1: 100 mg/mL (570.81 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

---

 (Please use freshly prepared in vivo formulations for optimal results.)