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Identification
NameL-Ornithine
Accession NumberDB00129  (NUTR00043)
Typesmall molecule
Groupsapproved, nutraceutical
Description

Ornithine is an amino acid produced in the urea cycle by the splitting off of urea from arginine. It is a central part of the urea cycle, which allows for the disposal of excess nitrogen. L-Ornithine is a precursor of citrulline and arginine.

Structure
Thumb
Synonyms
SynonymLanguageCode
(S)-2,5-DiaminopentanoateNot AvailableNot Available
(S)-2,5-Diaminopentanoic acidNot AvailableNot Available
(S)-2,5-diaminovaleric acidNot AvailableNot Available
(S)-ornithineNot AvailableNot Available
(S)-α,δ-diaminovaleric acidNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number70-26-8
WeightAverage: 132.161
Monoisotopic: 132.089877638
Chemical FormulaC5H12N2O2
InChI KeyAHLPHDHHMVZTML-BYPYZUCNSA-N
InChI
InChI=1S/C5H12N2O2/c6-3-1-2-4(7)5(8)9/h4H,1-3,6-7H2,(H,8,9)/t4-/m0/s1
IUPAC Name
(2S)-2,5-diaminopentanoic acid
SMILES
NCCC[C@H](N)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentAlpha Amino Acids and Derivatives
Alternative parentsAmino Fatty Acids; Enolates; Polyamines; Carboxylic Acids; Monoalkylamines
Substituentscarboxylic acid; enolate; polyamine; primary amine; amine; primary aliphatic amine; organonitrogen compound
Classification descriptionThis compound belongs to the alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
Pharmacology
IndicationUsed for nutritional supplementation, also for treating dietary shortage or imbalance. It has been claimed that ornithine improves athletic performance, has anabolic effects, has wound-healing effects, and is immuno-enhancing.
PharmacodynamicsA non-essential and nonprotein amino acid, ornithine is critical for the production of the body's proteins, enzymes and muscle tissue. Ornithine plays a central role in the urea cycle and is important for the disposal of excess nitrogen (ammonia). Ornithine is the starting point for the synthesis of many polyamines such as putrescine and spermine. Ornithine supplements are claimed to enhance the release of growth hormone and to burn excess body fat. Ornithine is necessary for proper immune function and good liver function.
Mechanism of actionL-Ornithine is metabolised to L-arginine. L-arginine stimulates the pituitary release of growth hormone. Burns or other injuries affect the state of L-arginine in tissues throughout the body. As De novo synthesis of L-arginine during these conditions is usually not sufficient for normal immune function, nor for normal protein synthesis, L-ornithine may have immunomodulatory and wound-healing activities under these conditions (by virtue of its metabolism to L-arginine).
AbsorptionAbsorbed from the small intestine via a sodium-dependent active transport process
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Ornithine undergoes extensive metabolism in the liver to L-arginine, polyamines, and proline, and several other metabolites.

SubstrateEnzymesProduct
L-Ornithine
Not Available
ProlineDetails
L-Ornithine
Not Available
L-ArginineDetails
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityOral, rat LD50 = 10000 mg/kg
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Argininosuccinic AciduriaDiseaseSMP00003
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)DiseaseSMP00362
L-arginine:glycine amidinotransferase deficiencyDiseaseSMP00507
Ornithine Aminotransferase Deficiency (OAT Deficiency)DiseaseSMP00363
Arginine and Proline MetabolismMetabolicSMP00020
Spermidine and Spermine BiosynthesisMetabolicSMP00445
ArgininemiaDiseaseSMP00357
Hyperornithinemia with gyrate atrophy (HOGA)DiseaseSMP00505
Carbamoyl Phosphate Synthetase DeficiencyDiseaseSMP00002
Citrullinemia Type IDiseaseSMP00001
Creatine deficiency, guanidinoacetate methyltransferase deficiencyDiseaseSMP00504
Urea CycleMetabolicSMP00059
Ornithine Transcarbamylase Deficiency (OTC Deficiency)DiseaseSMP00205
Prolidase Deficiency (PD)DiseaseSMP00207
Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)DiseaseSMP00188
Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome]DiseaseSMP00506
Hyperprolinemia Type IIDiseaseSMP00360
Hyperprolinemia Type IDiseaseSMP00361
Prolinemia Type IIDiseaseSMP00208
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.8449
Blood Brain Barrier + 0.7613
Caco-2 permeable - 0.7431
P-glycoprotein substrate Non-substrate 0.6568
P-glycoprotein inhibitor I Non-inhibitor 0.9856
P-glycoprotein inhibitor II Non-inhibitor 0.9681
Renal organic cation transporter Non-inhibitor 0.8847
CYP450 2C9 substrate Non-substrate 0.8464
CYP450 2D6 substrate Non-substrate 0.7517
CYP450 3A4 substrate Non-substrate 0.8238
CYP450 1A2 substrate Non-inhibitor 0.9653
CYP450 2C9 substrate Non-inhibitor 0.9639
CYP450 2D6 substrate Non-inhibitor 0.9786
CYP450 2C19 substrate Non-inhibitor 0.9659
CYP450 3A4 substrate Non-inhibitor 0.9327
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9931
Ames test AMES toxic 0.8541
Carcinogenicity Non-carcinogens 0.8407
Biodegradation Ready biodegradable 0.8711
Rat acute toxicity 1.0540 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9771
hERG inhibition (predictor II) Non-inhibitor 0.9663
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
CapsuleOral1000 mg
CapsuleOral500 mg
CapsuleOral650 mg
CapsuleOral750 mg
PowderOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point140 °CPhysProp
water solubilityAppreciableNot Available
logP-4.22SANGSTER (1994)
pKa1.94 (at 25 °C)KORTUM,G ET AL (1961)
Predicted Properties
PropertyValueSource
water solubility1.72e+02 g/lALOGPS
logP-3.6ALOGPS
logP-3.7ChemAxon
logS0.11ALOGPS
pKa (strongest acidic)2.67ChemAxon
pKa (strongest basic)10.29ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count3ChemAxon
polar surface area89.34ChemAxon
rotatable bond count4ChemAxon
refractivity33.21ChemAxon
polarizability13.85ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
References
Synthesis Reference

Takayasu Tsuchida, Haruo Uchibori, Yoshitaka Nishimoto, “Process and microorganism for producing L-ornithine by Corynebacterium, Brevibacterium, or Athrobacter.” U.S. Patent US5188947, issued January, 1970.

US5188947
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC01602
ChEBI15729
ChEMBL
PharmGKBPA164783814
IUPHAR725
Guide to Pharmacology725
HETORN
PDRhealthhttp://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/lor_0190.shtml
WikipediaOrnithine
ATC CodesA05BA06D11AX16P01CX03
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSshow(72.9 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Ornithine aminotransferase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Ornithine aminotransferase, mitochondrial P04181 Details

References:

  1. Levillain O, Balvay S, Peyrol S: Localization and differential expression of arginase II in the kidney of male and female mice. Pflugers Arch. 2005 Feb;449(5):491-503. Epub 2004 Dec 23. Pubmed
  2. Inubushi T, Takasawa T, Tuboi Y, Watanabe N, Aki K, Katunuma N: Changes of glucose metabolism and skin-collagen neogenesis in vitamin B6 deficiency. Biofactors. 2005;23(2):59-67. Pubmed
  3. Kaneko S, Ueda-Yamada M, Ando A, Matsumura S, Okuda-Ashitaka E, Matsumura M, Uyama M, Ito S: Cytotoxic effect of spermine on retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2007 Jan;48(1):455-63. Pubmed

2. Ornithine carbamoyltransferase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Ornithine carbamoyltransferase, mitochondrial P00480 Details

References:

  1. Barcelona-Andres B, Marina A, Rubio V: Gene structure, organization, expression, and potential regulatory mechanisms of arginine catabolism in Enterococcus faecalis. J Bacteriol. 2002 Nov;184(22):6289-300. Pubmed
  2. El Alami M, Dubois E, Oudjama Y, Tricot C, Wouters J, Stalon V, Messenguy F: Yeast epiarginase regulation, an enzyme-enzyme activity control: identification of residues of ornithine carbamoyltransferase and arginase responsible for enzyme catalytic and regulatory activities. J Biol Chem. 2003 Jun 13;278(24):21550-8. Epub 2003 Apr 4. Pubmed
  3. Templeton MD, Reinhardt LA, Collyer CA, Mitchell RE, Cleland WW: Kinetic analysis of the L-ornithine transcarbamoylase from Pseudomonas savastanoi pv. phaseolicola that is resistant to the transition state analogue®-N delta-(N’-sulfodiaminophosphinyl)-L-ornithine. Biochemistry. 2005 Mar 22;44(11):4408-15. Pubmed
  4. Morizono H, Cabrera-Luque J, Shi D, Gallegos R, Yamaguchi S, Yu X, Allewell NM, Malamy MH, Tuchman M: Acetylornithine transcarbamylase: a novel enzyme in arginine biosynthesis. J Bacteriol. 2006 Apr;188(8):2974-82. Pubmed

3. Arginase-1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Arginase-1 P05089 Details

References:

  1. Gobert AP, Cheng Y, Wang JY, Boucher JL, Iyer RK, Cederbaum SD, Casero RA Jr, Newton JC, Wilson KT: Helicobacter pylori induces macrophage apoptosis by activation of arginase II. J Immunol. 2002 May 1;168(9):4692-700. Pubmed
  2. Iwata S, Tsujino T, Ikeda Y, Ishida T, Ueyama T, Gotoh T, Mori M, Yokoyama M: Decreased expression of arginase II in the kidneys of Dahl salt-sensitive rats. Hypertens Res. 2002 May;25(3):411-8. Pubmed
  3. Stickings P, Mistry SK, Boucher JL, Morris SM, Cunningham JM: Arginase expression and modulation of IL-1beta-induced nitric oxide generation in rat and human islets of Langerhans. Nitric Oxide. 2002 Dec;7(4):289-96. Pubmed
  4. Bansal V, Ochoa JB: Arginine availability, arginase, and the immune response. Curr Opin Clin Nutr Metab Care. 2003 Mar;6(2):223-8. Pubmed
  5. El Alami M, Dubois E, Oudjama Y, Tricot C, Wouters J, Stalon V, Messenguy F: Yeast epiarginase regulation, an enzyme-enzyme activity control: identification of residues of ornithine carbamoyltransferase and arginase responsible for enzyme catalytic and regulatory activities. J Biol Chem. 2003 Jun 13;278(24):21550-8. Epub 2003 Apr 4. Pubmed

4. Ornithine decarboxylase antizyme 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Ornithine decarboxylase antizyme 1 P54368 Details

References:

  1. Lopez-Contreras AJ, Lopez-Garcia C, Jimenez-Cervantes C, Cremades A, Penafiel R: Mouse ornithine decarboxylase-like gene encodes an antizyme inhibitor devoid of ornithine and arginine decarboxylating activity. J Biol Chem. 2006 Oct 13;281(41):30896-906. Epub 2006 Aug 17. Pubmed
  2. Yamaguchi Y, Takatsuka Y, Matsufuji S, Murakami Y, Kamio Y: Characterization of a counterpart to Mammalian ornithine decarboxylase antizyme in prokaryotes. J Biol Chem. 2006 Feb 17;281(7):3995-4001. Epub 2005 Dec 14. Pubmed
  3. Janne J, Alhonen L, Pietila M, Keinanen TA: Genetic approaches to the cellular functions of polyamines in mammals. Eur J Biochem. 2004 Mar;271(5):877-94. Pubmed

5. Low affinity cationic amino acid transporter 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity cationic amino acid transporter 2 P52569 Details

References:

  1. Yeramian A, Martin L, Arpa L, Bertran J, Soler C, McLeod C, Modolell M, Palacin M, Lloberas J, Celada A: Macrophages require distinct arginine catabolism and transport systems for proliferation and for activation. Eur J Immunol. 2006 Jun;36(6):1516-26. Pubmed
  2. Cerec V, Piquet-Pellorce C, Aly HA, Touzalin AM, Jegou B, Bauche F: Multiple pathways for cationic amino Acid transport in rat seminiferous tubule cells. Biol Reprod. 2007 Feb;76(2):241-9. Epub 2006 Oct 25. Pubmed
  3. Endo M, Oyadomari S, Terasaki Y, Takeya M, Suga M, Mori M, Gotoh T: Induction of arginase I and II in bleomycin-induced fibrosis of mouse lung. Am J Physiol Lung Cell Mol Physiol. 2003 Aug;285(2):L313-21. Epub 2003 Apr 4. Pubmed

6. Mitochondrial ornithine transporter 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Mitochondrial ornithine transporter 2 Q9BXI2 Details

References:

  1. Camacho JA, Rioseco-Camacho N, Andrade D, Porter J, Kong J: Cloning and characterization of human ORNT2: a second mitochondrial ornithine transporter that can rescue a defective ORNT1 in patients with the hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, a urea cycle disorder. Mol Genet Metab. 2003 Aug;79(4):257-71. Pubmed
  2. Begum L, Jalil MA, Kobayashi K, Iijima M, Li MX, Yasuda T, Horiuchi M, del Arco A, Satrustegui J, Saheki T: Expression of three mitochondrial solute carriers, citrin, aralar1 and ornithine transporter, in relation to urea cycle in mice. Biochim Biophys Acta. 2002 Apr 12;1574(3):283-92. Pubmed
  3. Camacho JA, Mardach R, Rioseco-Camacho N, Ruiz-Pesini E, Derbeneva O, Andrade D, Zaldivar F, Qu Y, Cederbaum SD: Clinical and functional characterization of a human ORNT1 mutation (T32R) in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Pediatr Res. 2006 Oct;60(4):423-9. Epub 2006 Aug 28. Pubmed

7. Cationic amino acid transporter 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cationic amino acid transporter 4 O43246 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

8. High affinity cationic amino acid transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
High affinity cationic amino acid transporter 1 P30825 Details

References:

  1. Rotmann A, Strand D, Martine U, Closs EI: Protein kinase C activation promotes the internalization of the human cationic amino acid transporter hCAT-1. A new regulatory mechanism for hCAT-1 activity. J Biol Chem. 2004 Dec 24;279(52):54185-92. Epub 2004 Oct 15. Pubmed
  2. Cerec V, Piquet-Pellorce C, Aly HA, Touzalin AM, Jegou B, Bauche F: Multiple pathways for cationic amino Acid transport in rat seminiferous tubule cells. Biol Reprod. 2007 Feb;76(2):241-9. Epub 2006 Oct 25. Pubmed
  3. Yeramian A, Martin L, Arpa L, Bertran J, Soler C, McLeod C, Modolell M, Palacin M, Lloberas J, Celada A: Macrophages require distinct arginine catabolism and transport systems for proliferation and for activation. Eur J Immunol. 2006 Jun;36(6):1516-26. Pubmed

9. Arginase-2, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Arginase-2, mitochondrial P78540 Details

References:

  1. Rodriguez PC, Zea AH, DeSalvo J, Culotta KS, Zabaleta J, Quiceno DG, Ochoa JB, Ochoa AC: L-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes. J Immunol. 2003 Aug 1;171(3):1232-9. Pubmed
  2. Levillain O, Hus-Citharel A, Garvi S, Peyrol S, Reymond I, Mutin M, Morel F: Ornithine metabolism in male and female rat kidney: mitochondrial expression of ornithine aminotransferase and arginase II. Am J Physiol Renal Physiol. 2004 Apr;286(4):F727-38. Epub 2004 Feb 10. Pubmed
  3. Levillain O, Diaz JJ, Blanchard O, Dechaud H: Testosterone down-regulates ornithine aminotransferase gene and up-regulates arginase II and ornithine decarboxylase genes for polyamines synthesis in the murine kidney. Endocrinology. 2005 Feb;146(2):950-9. Epub 2004 Nov 11. Pubmed
  4. Bussiere FI, Chaturvedi R, Cheng Y, Gobert AP, Asim M, Blumberg DR, Xu H, Kim PY, Hacker A, Casero RA Jr, Wilson KT: Spermine causes loss of innate immune response to Helicobacter pylori by inhibition of inducible nitric-oxide synthase translation. J Biol Chem. 2005 Jan 28;280(4):2409-12. Epub 2004 Nov 17. Pubmed
  5. Nissim I, Luhovyy B, Horyn O, Daikhin Y, Nissim I, Yudkoff M: The role of mitochondrially bound arginase in the regulation of urea synthesis: studies with [U-15N4]arginine, isolated mitochondria, and perfused rat liver. J Biol Chem. 2005 May 6;280(18):17715-24. Epub 2005 Mar 7. Pubmed

10. Mitochondrial ornithine transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Mitochondrial ornithine transporter 1 Q9Y619 Details

References:

  1. Korman SH, Kanazawa N, Abu-Libdeh B, Gutman A, Tsujino S: Hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome with evidence of mitochondrial dysfunction due to a novel SLC25A15 (ORNT1) gene mutation in a Palestinian family. J Neurol Sci. 2004 Mar 15;218(1-2):53-8. Pubmed
  2. Camacho JA, Mardach R, Rioseco-Camacho N, Ruiz-Pesini E, Derbeneva O, Andrade D, Zaldivar F, Qu Y, Cederbaum SD: Clinical and functional characterization of a human ORNT1 mutation (T32R) in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Pediatr Res. 2006 Oct;60(4):423-9. Epub 2006 Aug 28. Pubmed

11. Cationic amino acid transporter 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cationic amino acid transporter 3 Q8WY07 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Hosokawa H, Sawamura T, Kobayashi S, Ninomiya H, Miwa S, Masaki T: Cloning and characterization of a brain-specific cationic amino acid transporter. J Biol Chem. 1997 Mar 28;272(13):8717-22. Pubmed

12. Ornithine decarboxylase antizyme 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Ornithine decarboxylase antizyme 2 O95190 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

13. Glycine amidinotransferase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Glycine amidinotransferase, mitochondrial P50440 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Thomasset N, Quash GA, Dore JF: The differential contribution of arginase and transamidinase to ornithine biosynthesis in two achromic human melanoma cell lines. FEBS Lett. 1982 Nov 1;148(1):63-6. Pubmed
  4. Natesan S, Reddy SR: Compensatory changes in enzymes of arginine metabolism during renal hypertrophy in mice. Comp Biochem Physiol B Biochem Mol Biol. 2001 Dec;130(4):585-95. Pubmed
  5. Mitruka BM, Costilow RN: Arginine and ornithine catabolism by Clostridium botulinum. J Bacteriol. 1967 Jan;93(1):295-301. Pubmed

14. Ornithine decarboxylase antizyme 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Ornithine decarboxylase antizyme 3 Q9UMX2 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08