Toxicity Summary
L-citrulline is converted to L-arginine by arginine succinate synthase. L-arginine then exerts 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), whose action is mainly 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 whose partial sequence is similar to cytochrome P-450 reductase. NOS exists in several 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.

Citrulline is the parent compound of citrulline compounds, consisting of ornithine linked to a carbamoyl group at the N(5) position. It is a hapten and a metabolite of the large flea (Daphnia magna). It is the conjugate acid of citrulline. DL-citrulline has been reported in Drosophila melanogaster, Mycoplasma gallisepticum, and several other organisms with relevant data. See also: Citrulline (note moved to).

C6H13N3O3

175.19

175.095

627-77-0

833

White to off-white solid powder

1.3±0.1 g/cm3

386.7±42.0 °C at 760 mmHg

242-244ºC (dec.)

187.7±27.9 °C

0.0±1.9 mmHg at 25°C

1.531

-1.53

4

4

5

12

171

0

C(CC(C(=O)O)N)CNC(=O)N

RHGKLRLOHDJJDR-UHFFFAOYSA-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)

2-amino-5-(carbamoylamino)pentanoic acid

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 :~25 mg/mL (~142.70 mM )

Solubility in Formulation 1: 25 mg/mL (142.70 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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