| Record Information |
| Version |
3.5 |
| Creation Date |
2005-11-16 08:48:42 -0700 |
| Update Date |
2013-02-08 17:09:33 -0700 |
| HMDB ID |
HMDB00904 |
| Secondary Accession Numbers |
None |
| Metabolite Identification |
| Common Name |
Citrulline |
| Description |
Citrulline is an amino acid 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 (NOS; EC 1.14.13.39). In this reaction arginine is first oxidized into N-hydroxyl-arginine, which is then further oxidized to citrulline concomitant with the release of nitric oxide. EC 1.14.13.39). Citrulline's name is derived from citrullus, the Latin word for watermelon, from which it was first isolated. |
| Structure |
Download:
MOL |
SDF |
SMILES |
InChI
Display:
2D Structure |
3D Structure
|
| Synonyms |
- (2S)-2-amino-5-(carbamoylamino)pentanoate
- (2S)-2-amino-5-(carbamoylamino)pentanoic acid
- (S)-2-amino-5-(aminocarbonyl)aminopentanoate
- (S)-2-amino-5-(aminocarbonyl)aminopentanoic acid
- (S)-2-Amino-5-ureidopentanoate
- (S)-2-Amino-5-ureidopentanoic acid
- 2-Amino-5-uredovalerate
- 2-Amino-5-uredovaleric acid
- 2-Amino-5-ureidovalerate
- 2-Amino-5-ureidovaleric acid
- A-Amino-D-ureidovalerate
- A-Amino-D-ureidovaleric acid
- alpha-Amino-delta-ureidovalerate
- alpha-Amino-delta-ureidovaleric acid
- alpha-Amino-gamma-ureidovalerate
- alpha-Amino-gamma-ureidovaleric acid
- Amino-ureidovalerate
- Amino-ureidovaleric acid
- CIR
- CIT
- Cytrulline
- D-Ureidonorvaline
- delta-Ureidonorvaline
- DL-citrulline
- Gammaureidonorvaline
- H-Cit-oh
- L(+)-2-Amino-5-ureidovalerate
- L(+)-2-Amino-5-ureidovaleric acid
- L(+)-Citrulline
- L-2-Amino-5-ureido-valerate
- L-2-Amino-5-ureido-valeric acid
- L-2-Amino-5-ureidovalerate
- L-2-Amino-5-ureidovaleric acid
- L-Citrulline
- L-Cytrulline
- L-N5-carbamoyl-Ornithine
- N()-Carbamylornithine
- N(5)-(Aminocarbonyl)-DL-Ornithine
- N(delta)-Carbamylornithine
- N-Carbamylornithine
- N5-(Aminocarbonyl)-L-ornithine
- N5-(aminocarbonyl)-Ornithine
- N5-(Aminocarbonyl)ornithine
- N5-Carbamoyl-L-ornithine
- N5-carbamoylornithine
- N5-carbamylornithine
- N<SUP>5</SUP>-(aminocarbonyl)ornithine
- ND-carbamylornithine
- Ndelta-carbamy-ornithine
- Ndelta-carbamylornithine
- Ngamma-carbamylornithine
- Sitrulline
- Ureidonorvaline
- Ureidovalerate
- Ureidovaleric acid
|
| Chemical Formula |
C6H13N3O3 |
| Average Molecular Weight |
175.1857 |
| Monoisotopic Molecular Weight |
175.095691297 |
| IUPAC Name |
(2S)-2-amino-5-(carbamoylamino)pentanoic acid |
| Traditional IUPAC Name |
L-citrulline |
| CAS Registry Number |
372-75-8 |
| SMILES |
N[C@@H](CCCNC(N)=O)C(O)=O |
| InChI Identifier |
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 |
| InChI Key |
RHGKLRLOHDJJDR-BYPYZUCNSA-N |
| Chemical Taxonomy |
| Kingdom |
Organic Compounds |
| Super Class |
Amino Acids, Peptides, and Analogues |
| Class |
Amino Acids and Derivatives |
| Sub Class |
Alpha Amino Acids and Derivatives |
| Other Descriptors |
- Aliphatic Acyclic Compounds
- citrullines(ChEBI)
|
| Substituents |
- Carboxylic Acid
- Polyamine
- Primary Aliphatic Amine (Alkylamine)
- Urea
|
| Direct Parent |
Alpha Amino Acids and Derivatives |
| Ontology |
| Status |
Detected and Quantified |
| Origin |
|
| Biofunction |
- Component of Alanine and aspartate metabolism
- Component of Arginine and proline metabolism
|
| Application |
Not Available |
| Cellular locations |
|
| Physical Properties |
| State |
Solid |
| Experimental Properties |
| Property |
Value |
Reference |
| Melting Point |
235.5 °C |
Not Available |
| Boiling Point |
Not Available |
Not Available |
| Water Solubility |
212 mg/mL |
Not Available |
| LogP |
-3.19 |
SANGSTER (1994) |
|
| Predicted Properties |
|
| Spectra |
|
| 13C NMR Spectrum |
| 1H NMR Spectrum |
| MS/MS Spectrum Quattro_QQQ 10 |
| MS/MS Spectrum Quattro_QQQ 25 |
| MS/MS Spectrum Quattro_QQQ 40 |
| MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) |
| MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) |
| MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) |
| MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) |
| MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) |
| MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) |
| MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) |
| MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) |
| MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) |
| MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) |
| MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) |
| MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) |
| [1H,1H] 2D NMR Spectrum |
| [1H,13C] 2D NMR Spectrum |
|
| Biological Properties |
| Cellular Locations |
|
| Biofluid Locations |
- Blood
- Cerebrospinal Fluid (CSF)
- Urine
|
| Tissue Location |
- Bladder
- Fibroblasts
- Intestine
- Neuron
- Placenta
- Kidney
- Liver
- Epidermis
- Myelin
- Prostate
- Nerve Cells
- Platelet
|
| Pathways |
|
| Normal Concentrations |
|
| Blood |
Detected and Quantified |
|
38.0 (30.0-46.0) uM |
Adult (>18 years old) |
Both |
Normal |
Not Available |
| Blood |
Detected and Quantified |
|
36.0 +/- 8.0 uM |
Children (1-13 year old) |
Male |
Normal |
Not Available |
| Blood |
Detected and Quantified |
|
37.0 +/- 9.0 uM |
Adult (>18 years old) |
Male |
Normal |
Not Available |
| Blood |
Detected and Quantified |
|
35.0 +/- 10.0 uM |
Adult (>18 years old) |
Female |
Normal |
Not Available |
| Blood |
Detected and Quantified |
|
38.0 (30.0-46.0) uM |
Adult (>18 years old) |
Not Specified |
Normal |
Not Available |
| Cerebrospinal Fluid (CSF) |
Detected and Quantified |
|
2.8 +/- 1.0 uM |
Adult (>18 years old) |
Male |
Normal |
Not Available |
| Cerebrospinal Fluid (CSF) |
Detected and Quantified |
|
2.8 +/- 1.8 uM |
Adult (>18 years old) |
Not Specified |
Normal |
Not Available |
| Cerebrospinal Fluid (CSF) |
Detected and Quantified |
|
2.62 (1.35-3.89) uM |
Adult (>18 years old) |
Both |
Normal |
Not Available |
| Cerebrospinal Fluid (CSF) |
Detected and Quantified |
|
5.81+/- 1.23 uM |
Adult (>18 years old) |
Both |
Normal |
Not Available |
| Cerebrospinal Fluid (CSF) |
Detected and Quantified |
|
1.5 +/- 0.5 uM |
Adult (>18 years old) |
Both |
Normal |
Not Available |
| Urine |
Detected and Quantified |
|
1.08 (0.065-2.1) umol/mmol creatinine |
Adult (>18 years old) |
Both |
Normal |
Not Available |
| Urine |
Detected and Quantified |
|
0.19 umol/mmol creatinine |
Adult (>18 years old) |
Both |
Normal |
Not Available |
| Urine |
Detected and Quantified |
|
0.00-74.25 umol/mmol creatinine |
Adult (>18 years old) |
Both |
Normal |
Not Available |
| Urine |
Detected and Quantified |
|
0.50 +/- 0.54 umol/mmol creatinine |
Children (1-13 year old) |
Male |
Normal |
Not Available |
| Urine |
Detected and Quantified |
|
1.1 +/- 0.84 umol/mmol creatinine |
Adult (>18 years old) |
Male |
Normal |
Not Available |
| Urine |
Detected and Quantified |
|
0.99 +/- 0.69 umol/mmol creatinine |
Adult (>18 years old) |
Female |
Normal |
Not Available |
| Urine |
Detected and Quantified |
|
0.24 +/- 0.23 umol/mmol creatinine |
Adult (>18 years old) |
Both |
Normal |
Not Available |
| Urine |
Detected and Quantified |
|
0.8 (0.2-1.7) umol/mmol creatinine |
Adult (>18 years old) |
Both |
Normal |
by LC-MS/MS (Biocrates kit)
|
|
| Abnormal Concentrations |
|
| Blood |
Detected and Quantified |
|
10.00 (5.00-15.00) uM |
Adult (>18 years old) |
Both |
N-Acetylglutamate synthetase deficiency |
Not Available |
| Blood |
Detected and Quantified |
|
27.5 (10.0-45.0) uM |
Adult (>18 years old) |
Both |
Argininosuccinic aciduria (ASL) |
Not Available |
| Blood |
Detected and Quantified |
|
200.0 (100.0-300.0) uM |
Adult (>18 years old) |
Both |
Argininosuccinic aciduria (ASL) |
Not Available |
| Blood |
Detected and Quantified |
|
13.0 (6.0-20.0) uM |
Adult (>18 years old) |
Both |
Permanent intestinal failure |
Not Available |
| Blood |
Detected and Quantified |
|
25.4 (23.4-27.4) uM |
Adult (>18 years old) |
Both |
Seizures |
Acute seizures
|
| Blood |
Detected and Quantified |
|
26.8 (25.4-28.2) uM |
Adult (>18 years old) |
Both |
Epilepsy |
Refractory localization-related epilepsy (RLE)
|
| Blood |
Detected and Quantified |
|
26.9 (25.2-28.6) uM |
Children (1-13 year old) |
Both |
Epilepsy |
Juvenile myoclonic epilepsy (JME)
|
| Blood |
Detected and Quantified |
|
94.97 +/- 11.18 uM |
Elderly (>65 years old) |
Both |
Alzheimer's disease |
Not Available |
| Cerebrospinal Fluid (CSF) |
Detected and Quantified |
|
27.0 +/- 2.6 uM |
Adult (>18 years old) |
Both |
Alzheimer's disease |
Not Available |
| Cerebrospinal Fluid (CSF) |
Detected and Quantified |
|
5.38 +/- 0.94 uM |
Adult (>18 years old) |
Both |
Schizophrenia |
Not Available |
| Urine |
Detected and Quantified |
|
21.0 +/- 2.8 umol/mmol creatinine |
Adult (>18 years old) |
Both |
Alzheimer's disease |
Not Available |
|
| Associated Disorders and Diseases |
| Disease References |
| Intestinal failure |
- Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B: Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology. 2000 Dec;119(6):1496-505.
Pubmed: 11113071
|
| Epilepsy |
- Rainesalo S, Keranen T, Palmio J, Peltola J, Oja SS, Saransaari P: Plasma and cerebrospinal fluid amino acids in epileptic patients. Neurochem Res. 2004 Jan;29(1):319-24.
Pubmed: 14992292
|
| Alzheimer's disease |
- Fonteh AN, Harrington RJ, Tsai A, Liao P, Harrington MG: Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease subjects. Amino Acids. 2007 Feb;32(2):213-24. Epub 2006 Oct 10.
Pubmed: 17031479
|
| Schizophrenia |
- Do KQ, Lauer CJ, Schreiber W, Zollinger M, Gutteck-Amsler U, Cuenod M, Holsboer F: gamma-Glutamylglutamine and taurine concentrations are decreased in the cerebrospinal fluid of drug-naive patients with schizophrenic disorders. J Neurochem. 1995 Dec;65(6):2652-62.
Pubmed: 7595563
|
| Argininosuccinic aciduria |
- http://www.metagene.de/program/d.prg?mp=ARGININOSUCCINIC%20ACIDURIA%20(ASL)
|
| N-acetylglutamate synthetase deficiency |
- http://www.metagene.de/program/d.prg?mp=N-ACETYLGLUTAMATE%20SYNTHETASE%20DEFICIENCY.%20NAGS%20DEFICIENCY
|
|
| Associated OMIM IDs |
- 104300
(Alzheimer's disease)
- 207900
(Argininosuccinic aciduria)
- 181500
(Schizophrenia)
- 608300
(N-acetylglutamate synthetase deficiency)
|
| External Links |
| DrugBank ID |
DB00155  |
| Phenol Explorer Compound ID |
Not Available |
| Phenol Explorer Metabolite ID |
Not Available |
| FoodDB ID |
FDB011841 |
| KNApSAcK ID |
C00001348  |
| Chemspider ID |
9367  |
| KEGG Compound ID |
C00327  |
| BioCyc ID |
L-CITRULLINE  |
| BiGG ID |
34627  |
| Wikipedia Link |
Citrulline  |
| NuGOwiki Link |
HMDB00904  |
| Metagene Link |
HMDB00904  |
| METLIN ID |
16  |
| PubChem Compound |
9750  |
| PDB ID |
CIR  |
| ChEBI ID |
16349  |
| References |
| Synthesis Reference |
Kakimoto, Toshio; Shibatani, Takeji; Nishimura, Noriyuki; Chibata, Ichiro. Enzymic production of L-citrulline by Pseudomonas putida. Applied Microbiology (1971), 22(6), 992-9. |
| Material Safety Data Sheet (MSDS) |
Download (PDF)
|
| General References |
- DeLong GR, Glick TH: Ammonia metabolism in Reye syndrome and the effect of citrulline. Ann Neurol. 1982 Jan;11(1):53-8.
Pubmed: 7059128
- Jianfeng G, Weiming Z, Ning L, Fangnan L, Li T, Nan L, Jieshou L: Serum citrulline is a simple quantitative marker for small intestinal enterocytes mass and absorption function in short bowel patients. J Surg Res. 2005 Aug;127(2):177-82.
Pubmed: 15921697
- Cynober LA: Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance. Nutrition. 2002 Sep;18(9):761-6.
Pubmed: 12297216
- Liappis N, Pohl B, Weber HP, el-Karkani H: [Free amino acids in the saliva of children with phenylketonuria] Klin Padiatr. 1986 Jan-Feb;198(1):25-8.
Pubmed: 3959486
- Rainesalo S, Keranen T, Palmio J, Peltola J, Oja SS, Saransaari P: Plasma and cerebrospinal fluid amino acids in epileptic patients. Neurochem Res. 2004 Jan;29(1):319-24.
Pubmed: 14992292
- Fleisher LD, Harris CJ, Mitchell DA, Nadler HL: Citrullinemia: prenatal diagnosis of an affected fetus. Am J Hum Genet. 1983 Jan;35(1):85-90.
Pubmed: 6823975
- Potter MA, Zeesman S, Brennan B, Kobayashi K, Gao HZ, Tabata A, Saheki T, Whelan DT: Pregnancy in a healthy woman with untreated citrullinemia. Am J Med Genet A. 2004 Aug 15;129(1):77-82.
Pubmed: 15266621
- Wheatley DN, Kilfeather R, Stitt A, Campbell E: Integrity and stability of the citrulline-arginine pathway in normal and tumour cell lines. Cancer Lett. 2005 Sep 28;227(2):141-52.
Pubmed: 16112417
- Melis GC, Boelens PG, van der Sijp JR, Popovici T, De Bandt JP, Cynober L, van Leeuwen PA: The feeding route (enteral or parenteral) affects the plasma response of the dipetide Ala-Gln and the amino acids glutamine, citrulline and arginine, with the administration of Ala-Gln in preoperative patients. Br J Nutr. 2005 Jul;94(1):19-26.
Pubmed: 16115328
- Reparon-Schuijt CC, van Esch WJ, van Kooten C, Schellekens GA, de Jong BA, van Venrooij WJ, Breedveld FC, Verweij CL: Secretion of anti-citrulline-containing peptide antibody by B lymphocytes in rheumatoid arthritis. Arthritis Rheum. 2001 Jan;44(1):41-7.
Pubmed: 11212174
- Maruyama H, Ogawa M, Nishio T, Kobayashi K, Saheki T, Sunohara N: Citrullinemia type II in a 64-year-old man with fluctuating serum citrulline levels. J Neurol Sci. 2001 Jan 1;182(2):167-70.
Pubmed: 11137523
- McLaurin J, Moscarello MA: The preparation of antibodies reactive against citrulline-containing charge isomers of myelin basic protein but not against the arginine-containing charge isomers. Anal Biochem. 1990 Dec;191(2):272-7.
Pubmed: 1707596
- Facchinetti F, Longo M, Piccinini F, Neri I, Volpe A: L-arginine infusion reduces blood pressure in preeclamptic women through nitric oxide release. J Soc Gynecol Investig. 1999 Jul-Aug;6(4):202-7.
Pubmed: 10486782
- Origuchi Y, Ushijima T, Sakaguchi M, Akaboshi I, Matsuda I: Citrullinemia presenting as uncontrollable epilepsy. Brain Dev. 1984;6(3):328-31.
Pubmed: 6486381
- Booth FA, Haworth JC, Dilling LA, Perry TL, Greenberg CR, Seargeant LE, Penn AM, Rhead WJ: Mitochondrial encephalomyopathy with associated aminoacidopathy in a male sibship. J Pediatr. 1989 Jul;115(1):81-8.
Pubmed: 2738799
- Engelborghs S, Marescau B, De Deyn PP: Amino acids and biogenic amines in cerebrospinal fluid of patients with Parkinson's disease. Neurochem Res. 2003 Aug;28(8):1145-50.
Pubmed: 12834252
- Le Boucher J, Charret C, Coudray-Lucas C, Giboudeau J, Cynober L: Amino acid determination in biological fluids by automated ion-exchange chromatography: performance of Hitachi L-8500A. Clin Chem. 1997 Aug;43(8 Pt 1):1421-8.
Pubmed: 9267323
- Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B: Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology. 2000 Dec;119(6):1496-505.
Pubmed: 11113071
- Hagenfeldt L, Bjerkenstedt L, Edman G, Sedvall G, Wiesel FA: Amino acids in plasma and CSF and monoamine metabolites in CSF: interrelationship in healthy subjects. J Neurochem. 1984 Mar;42(3):833-7.
Pubmed: 6198473
- Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4.
Pubmed: 19212411
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| Enzymes |
| Name: |
Argininosuccinate synthase
|
| Reactions: |
- ATP + L-citrulline + L-aspartate = AMP + diphosphate + 2-(Nomega-L-arginino)succinate [RN:R01954]
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| Gene Name: |
ASS1 |
| Uniprot ID: |
P00966  |
| Protein Sequence: |
FASTA |
| Gene Sequence: |
FASTA |
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| Name: |
Argininosuccinate synthase
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| Reactions: |
- ATP + L-citrulline + L-aspartate = AMP + diphosphate + 2-(Nomega-L-arginino)succinate [RN:R01954]
|
| Gene Name: |
ASS1 |
| Uniprot ID: |
Q5T6L4  |
| Protein Sequence: |
FASTA |
| Gene Sequence: |
FASTA |
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