Citrulline
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Basic Info
| Common Name | Citrulline(F05328) |
| 2D Structure | |
| Description | Citrulline is an amino acid. It 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 by-product of the reaction catalyzed by NOS family. Its name is derived from citrullus, the Latin word for watermelon, from which it was first isolated. |
| FRCD ID | F05328 |
| CAS Number | 372-75-8 |
| PubChem CID | 9750 |
| Formula | C6H13N3O3 |
| IUPAC Name | (2S)-2-amino-5-(carbamoylamino)pentanoic acid |
| InChI Key | RHGKLRLOHDJJDR-BYPYZUCNSA-N |
| InChI | 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 |
| Canonical SMILES | C(CC(C(=O)O)N)CNC(=O)N |
| Isomeric SMILES | C(C[C@@H](C(=O)O)N)CNC(=O)N |
| Wikipedia | Citrulline |
| Synonyms |
N5-Carbamoyl-L-ornithine
L-citrulline
citrulline
372-75-8
delta-Ureidonorvaline
Sitrulline
H-cit-oh
L-Cytrulline
N5-(Aminocarbonyl)ornithine
N(delta)-Carbamylornithine
|
| Classifies |
Animal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organic acids and derivatives |
| Class | Carboxylic acids and derivatives |
| Subclass | Amino acids, peptides, and analogues |
| Intermediate Tree Nodes | Amino acids and derivatives - Alpha amino acids and derivatives - Alpha amino acids |
| Direct Parent | L-alpha-amino acids |
| Alternative Parents | |
| Molecular Framework | Aliphatic acyclic compounds |
| Substituents | L-alpha-amino acid - Fatty acid - Isourea - Amino acid - Carboximidic acid derivative - Carboxylic acid - Monocarboxylic acid or derivatives - Carboximidamide - Amine - Hydrocarbon derivative - Primary amine - Organooxygen compound - Organonitrogen compound - Organic oxide - Primary aliphatic amine - Organopnictogen compound - Imine - Organic oxygen compound - Organic nitrogen compound - Carbonyl group - Aliphatic acyclic compound |
| Description | This compound belongs to the class of organic compounds known as l-alpha-amino acids. These are alpha amino acids which have the L-configuration of the alpha-carbon atom. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 175.188 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 5 |
| Complexity | 171 |
| Monoisotopic Mass | 175.096 |
| Exact Mass | 175.096 |
| XLogP | -4.3 |
| Formal Charge | 0 |
| Heavy Atom Count | 12 |
| Defined Atom Stereocenter Count | 1 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.8961 |
| Human Intestinal Absorption | HIA+ | 0.6863 |
| Caco-2 Permeability | Caco2- | 0.8130 |
| P-glycoprotein Substrate | Non-substrate | 0.6160 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9782 |
| Non-inhibitor | 0.9820 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9331 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.6272 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7522 |
| CYP450 2D6 Substrate | Non-substrate | 0.7828 |
| CYP450 3A4 Substrate | Non-substrate | 0.8127 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9415 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9149 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9700 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9018 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8309 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9896 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9720 |
| Non-inhibitor | 0.9716 | |
| AMES Toxicity | Non AMES toxic | 0.5916 |
| Carcinogens | Non-carcinogens | 0.9113 |
| Fish Toxicity | Low FHMT | 0.8811 |
| Tetrahymena Pyriformis Toxicity | Low TPT | 0.9757 |
| Honey Bee Toxicity | Low HBT | 0.7825 |
| Biodegradation | Ready biodegradable | 0.9247 |
| Acute Oral Toxicity | IV | 0.5275 |
| Carcinogenicity (Three-class) | Non-required | 0.7143 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -1.1989 | LogS |
| Caco-2 Permeability | -0.0994 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 1.3397 | LD50, mol/kg |
| Fish Toxicity | 2.7097 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | -0.7355 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Determining optimal therapy of dogs with chronic enteropathy by measurement ofserum citrulline. | J Vet Intern Med | 2018 May | 29663515 |
| Ethyl carbamate in Swedish and American smokeless tobacco products and somefactors affecting its concentration. | Chem Cent J | 2018 Jul 24 | 30043180 |
| Citrulline decreases hepatic endotoxin-induced injury in fructose-induced non-alcoholic liver disease: an ex vivo study in the isolated perfused rat liver. | Br J Nutr | 2017 Jun | 28637520 |
| Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by Arginine and Glucose in Clostridium botulinum ATCC 3502. | Appl Environ Microbiol | 2017 Jul 1 | 28455330 |
| Nitric oxide production by peritoneal macrophages from aged rats: A short term and direct modulation by citrulline. | Biochimie | 2017 Feb | 27939527 |
| Oral citrulline supplementation protects female mice from the development of non-alcoholic fatty liver disease (NAFLD). | Eur J Nutr | 2017 Dec | 27496089 |
| Jugular-infused methionine, lysine and branched-chain amino acids does notimprove milk production in Holstein cows experiencing heat stress. | Animal | 2017 Dec | 28514978 |
| Neonatal Citrulline Supplementation and Later Exposure to a High Fructose Diet inRats Born with a Low Birth Weight: A Preliminary Report. | Nutrients | 2017 Apr 11 | 28398243 |
| Oral aversion to dietary sugar, ethanol and glycerol correlates with alterations in specific hepatic metabolites in a mouse model of human citrin deficiency. | Mol Genet Metab | 2017 Apr | 28259708 |
| Supplemental Citrulline Is More Efficient Than Arginine in Increasing SystemicArginine Availability in Mice. | J Nutr | 2017 Apr | 28179487 |
| Short-term dietary methionine supplementation affects one-carbon metabolism and DNA methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology. | Genes Nutr | 2017 | 28904640 |
| Roles of export genes cgmA and lysE for the production of L-arginine and L-citrulline by Corynebacterium glutamicum. | Appl Microbiol Biotechnol | 2016 Oct | 27350619 |
| Metabolic and clinical response to Escherichia coli lipopolysaccharide in layer pullets of different genetic backgrounds supplied with graded dietary L-arginine. | Poult Sci | 2016 Mar | 26740139 |
| Effect of specific amino acids on hepatic lipid metabolism in fructose-inducednon-alcoholic fatty liver disease. | Clin Nutr | 2016 Feb | 25736031 |
| Changes in the metabolome of rats after exposure to arginine andN-carbamylglutamate in combination with diquat, a compound that causes oxidative stress, assessed by 1H NMR spectroscopy. | Food Funct | 2016 Feb | 26732548 |
| The Importance of Quality Specifications in Safety Assessments of Amino Acids: The Cases of l-Tryptophan and l-Citrulline. | J Nutr | 2016 Dec | 27934657 |
| Doxorubicin-Induced Gut Toxicity in Piglets Fed Bovine Milk and Colostrum. | J Pediatr Gastroenterol Nutr | 2016 Dec | 27027906 |
| Lysozyme affects the microbial catabolism of free arginine in raw-milk hardcheeses. | Food Microbiol | 2016 Aug | 27052697 |
| Combining citrulline with atorvastatin preserves glucose homeostasis in a murine model of diet-induced obesity. | Br J Pharmacol | 2015 Oct | 26228176 |
| A metabolomics approach to the identification of biomarkers of sugar-sweetenedbeverage intake. | Am J Clin Nutr | 2015 Mar | 25733631 |
Targets
- General Function:
- Protein-arginine deiminase activity
- Specific Function:
- Catalyzes the deimination of arginine residues of proteins. May be involved in cytoskeletal reorganization in the egg and early embryo (By similarity).
- Gene Name:
- PADI6
- Uniprot ID:
- Q6TGC4
- Molecular Weight:
- 77726.735 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Protein-arginine deiminase activity
- Specific Function:
- Catalyzes the deimination of arginine residues of proteins.
- Gene Name:
- PADI1
- Uniprot ID:
- Q9ULC6
- Molecular Weight:
- 74664.97 Da
References
- Iida A, Nakamura Y: Identification of 45 novel SNPs in the 83-kb region containing peptidylarginine deiminase types 1 and 3 loci on chromosomal band 1p36.13. J Hum Genet. 2004;49(7):387-90. Epub 2004 May 19. [15150696 ]
- General Function:
- Protein-arginine deiminase activity
- Specific Function:
- Catalyzes the deimination of arginine residues of proteins.
- Gene Name:
- PADI2
- Uniprot ID:
- Q9Y2J8
- Molecular Weight:
- 75563.35 Da
References
- Dong S, Kojima T, Shiraiwa M, Mechin MC, Chavanas S, Serre G, Simon M, Kawada A, Takahara H: Regulation of the expression of peptidylarginine deiminase type II gene (PADI2) in human keratinocytes involves Sp1 and Sp3 transcription factors. J Invest Dermatol. 2005 May;124(5):1026-33. [15854045 ]
- General Function:
- Toxic substance binding
- Specific Function:
- Is indirectly involved in the control of blood pressure.
- Gene Name:
- ASS1
- Uniprot ID:
- P00966
- Molecular Weight:
- 46530.055 Da
References
- Braissant O, Honegger P, Loup M, Iwase K, Takiguchi M, Bachmann C: Hyperammonemia: regulation of argininosuccinate synthetase and argininosuccinate lyase genes in aggregating cell cultures of fetal rat brain. Neurosci Lett. 1999 May 7;266(2):89-92. [10353334 ]
- General Function:
- Toxic substance binding
- Gene Name:
- ASS
- Uniprot ID:
- Q5T6L4
- Molecular Weight:
- 46530.055 Da
References
- Husson A, Brasse-Lagnel C, Fairand A, Renouf S, Lavoinne A: Argininosuccinate synthetase from the urea cycle to the citrulline-NO cycle. Eur J Biochem. 2003 May;270(9):1887-99. [12709047 ]
- General Function:
- Tetrahydrobiopterin binding
- Specific Function:
- Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.
- Gene Name:
- NOS3
- Uniprot ID:
- P29474
- Molecular Weight:
- 133287.62 Da
References
- Hayakawa H, Raij L: Relationship between hypercholesterolaemia, endothelial dysfunction and hypertension. J Hypertens. 1999 May;17(5):611-9. [10403604 ]
- General Function:
- Tetrahydrobiopterin binding
- Specific Function:
- Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2. As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on 'Cys-247' implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM.
- Gene Name:
- NOS2
- Uniprot ID:
- P35228
- Molecular Weight:
- 131116.3 Da
References
- Keilhoff G, Reiser M, Stanarius A, Aoki E, Wolf G: Citrulline immunohistochemistry for demonstration of NOS activity in vivo and in vitro. Nitric Oxide. 2000 Aug;4(4):343-53. [10944418 ]
- General Function:
- Metal ion binding
- Specific Function:
- Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.
- Gene Name:
- DDAH1
- Uniprot ID:
- O94760
- Molecular Weight:
- 31121.5 Da
References
- Tran CT, Fox MF, Vallance P, Leiper JM: Chromosomal localization, gene structure, and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins. Genomics. 2000 Aug 15;68(1):101-5. [10950934 ]
- General Function:
- Protein-arginine deiminase activity
- Specific Function:
- Catalyzes the deimination of arginine residues of proteins.
- Gene Name:
- PADI3
- Uniprot ID:
- Q9ULW8
- Molecular Weight:
- 74742.705 Da
References
- Iida A, Nakamura Y: Identification of 45 novel SNPs in the 83-kb region containing peptidylarginine deiminase types 1 and 3 loci on chromosomal band 1p36.13. J Hum Genet. 2004;49(7):387-90. Epub 2004 May 19. [15150696 ]
- General Function:
- Dimethylargininase activity
- Specific Function:
- Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.
- Gene Name:
- DDAH2
- Uniprot ID:
- O95865
- Molecular Weight:
- 29643.54 Da
References
- Tran CT, Fox MF, Vallance P, Leiper JM: Chromosomal localization, gene structure, and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins. Genomics. 2000 Aug 15;68(1):101-5. [10950934 ]
- General Function:
- Phospholipid binding
- Gene Name:
- OTC
- Uniprot ID:
- P00480
- Molecular Weight:
- 39934.775 Da
References
- Quintero MJ, Muro-Pastor AM, Herrero A, Flores E: Arginine catabolism in the cyanobacterium Synechocystis sp. Strain PCC 6803 involves the urea cycle and arginase pathway. J Bacteriol. 2000 Feb;182(4):1008-15. [10648527 ]
- General Function:
- Tetrahydrobiopterin binding
- Specific Function:
- Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.
- Gene Name:
- NOS1
- Uniprot ID:
- P29475
- Molecular Weight:
- 160969.095 Da
References
- Kominami S, Yamazaki T, Koga T, Hori H: EPR studies on the photo-induced intermediates of ferric NO complexes of rat neuronal nitric oxide synthase trapped at low temperature. J Biochem. 1999 Oct;126(4):756-61. [10502685 ]
- General Function:
- Protein-arginine deiminase activity
- Specific Function:
- Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance. Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci). Acts as a key regulator of stem cell maintenance by mediating citrullination of histone H1: citrullination of 'Arg-54' of histone H1 (H1R54ci) results in H1 displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance. Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci. Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.
- Gene Name:
- PADI4
- Uniprot ID:
- Q9UM07
- Molecular Weight:
- 74078.65 Da
References
- Wang Y, Wysocka J, Sayegh J, Lee YH, Perlin JR, Leonelli L, Sonbuchner LS, McDonald CH, Cook RG, Dou Y, Roeder RG, Clarke S, Stallcup MR, Allis CD, Coonrod SA: Human PAD4 regulates histone arginine methylation levels via demethylimination. Science. 2004 Oct 8;306(5694):279-83. Epub 2004 Sep 2. [15345777 ]