It is also produced from L-arginine as a by-product of the reaction catalyzed by the enzyme NO synthase.
Handbook of experimental pharmacology Series by Roger G. Pertwee
L-citrulline, while being an amino acid, is not involved in protein synthesis and is not one of the amino acids coded for by DNA. Although citrulline cannot be incorporated in proteins during protein synthesis, several proteins are known to contain citrulline as an amino acid. These citrulline residues are generated by a family of enzymes called peptidylarginine deiminases PADs , which convert the amino acid arginine into citrulline. Proteins that contain citrulline residues include myelin basic protein MBP , fillagrin and several histone proteins.
L-citrulline is converted to L-arginine by argininosuccinate synthase. L-arginine is in turn responsible for citrulline's therapeutic affects.
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Many of L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NOS is a heme-containing enzyme with some sequences similar to cytochrome P reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli.
All the nitric oxide synthases use NADPH reduced nicotinamide adenine dinucleotide phosphate and oxygen O 2 as cosubstrates, as well as the cofactors FAD flavin adenine dinucleotide , FMN flavin mononucleotide , tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range.
The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid would make any difference with regard to NO production.
The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e. Comprehensive structured data on known drug adverse effects with statistical prevalence. Structured data covering drug contraindications.
Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more. Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects. Extended description of the mechanism of action and particular properties of each drug interaction.
An effect category for each drug interaction. Know how this interaction affects the subject drug. Patent US, issued June 04, There is additional data available for commercial users including Adverse Effects, Contraindications, and Blackbox Warnings. Contact us to learn more about these and other features. Jump to section. L-Citrulline Targets 13 Transporters 1 Biointeractions 1. Adverse Effects. Blackbox Warnings.
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist. Drug Interaction. Extended Description. Evidence Level. Retrieved 22 December Annals of Internal Medicine. Retrieved 11 June Archived from the original on 12 January Retrieved 3 April Archived from the original on 6 January Oxford Handbook of Practical Drug Therapy.
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