5-Hydroxy-L-tryptophan (T3D4298)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2014-08-29 06:16:56 UTC
Update Date2018-03-21 17:46:16 UTC
Accession NumberT3D4298
Identification
Common Name5-Hydroxy-L-tryptophan
ClassSmall Molecule
Description5-Hydroxy-L-tryptophan is an aromatic amino acid naturally produced by the body from the essential amino acid L-tryptophan. 5-Hydroxy-L-tryptophan is the immediate precursor of the neurotransmitter serotonin. The conversion to serotonin is catalyzed by the enzyme aromatic L-amino acid decarboxylase (EC 4.1.1.28) (AADC1 also known as DOPA decarboxylase), an essential enzyme in the metabolism of the monoamine neurotransmitters. An accumulation of 5-hydroxy-L-tryptophan in cerebrospinal fluid occurs in aromatic L-amino acid decarboxylase deficiency (AADC deficiency) (OMIM: 608643) accompanied by an increased excretion in the urine of the patients, which are indicative of the disorder but not specific. 5-Hydroxy-L-tryptophan is also increased in other disorders such as in Parkinson's patients with severe postural instability and gait disorders. The amount of endogenous 5-hydroxy-L-tryptophan available for serotonin synthesis depends on the availability of tryptophan and on the activity of various enzymes, especially tryptophan hydroxylase (EC 1.14.16.4), indoleamine 2,3-dioxygenase (EC 1.13.11.52), and tryptophan 2,3-dioxygenase (TDO) (EC 1.13.11.11). 5-Hydroxy-L-tryptophan has been used clinically for over 30 years. In addition to its use in the treatment of depression, the therapeutic administration of 5-hydroxy-L-tryptophan has been shown to be effective in treating a wide variety of conditions, including fibromyalgia, insomnia, binge eating associated with obesity, cerebellar ataxia, and chronic headaches. 5-Hydroxy-L-tryptophan easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. Supplementation with 5-hydroxy-L-tryptophan is hypothesized to normalize serotonin synthesis, which is putatively related to its antidepressant properties (PMID: 9295177, 17240182, 16023217). When present in sufficiently high levels, 5-hydroxytryptophan can be a neurotoxin and a metabotoxin. A neurotoxin is a compound that disrupts or attacks neural cells or tissue. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Signs and symptoms of AADC deficiency generally appear in the first year of life. Affected infants may have severe developmental delay, weak muscle tone (hypotonia), muscle stiffness, difficulty moving, and involuntary writhing movements of the limbs (athetosis). They may be lacking in energy (lethargic), feed poorly, startle easily, and have sleep disturbances. Since 5-hydroxytryptophan is a precursor to serotonin, altered levels of serotonin can accumulate in the brain, which leads to abnormal neural signalling. Infants with AADC deficiency have very low levels of neural signalling molecules while individuals who consume high levels of 5-hydroxytryptophan will have very high levels of neural signalling molecules. Both conditions can lead to vomiting, nausea, extreme drowsiness, and lethargy. 5-Hydroxytryptophan (5-HTP), also known as oxitriptan (INN) is sold over-the-counter in the United Kingdom, the United States, and Canada as a dietary supplement for use as an antidepressant, appetite suppressant, and sleep aid. It is also marketed in many European countries for the indication of major depression under trade names such as Cincofarm, Levothym, Levotonine, Oxyfan, Telesol, Tript-OH, and Triptum. Several double-blind placebo-controlled clinical trials have demonstrated the effectiveness of 5-HTP in the treatment of depression, though a lack of high-quality studies has been noted. More and larger studies are needed to determine if 5-HTP is truly effective in treating depression.
Compound Type
  • Amine
  • Animal Toxin
  • Antidepressive Agent, Second-Generation
  • Drug
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Nutraceutical
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(+-)-5-Hydroxytryptophan
(S)-5-Hydroxytryptophan
5-Hydroxy-tryptophan
5-Hydroxyl-L-tryptophan
5-Hydroxytryptophan
5-Hydroxytryptophan L form
5-Hydroxytryptophan L-form
Cincofarm
Hydroxy-5 L-tryptophane
Hydroxytryptophan
L-5-Hydroxytryptophan
Levothym
Levotinine
Oxitriptan
Oxyfan
Oxytryptophan
Pretonine
Quietim
Serotonyl
Telesol
Tript-OH
Triptene
Chemical FormulaC11H12N2O3
Average Molecular Mass220.225 g/mol
Monoisotopic Mass220.085 g/mol
CAS Registry Number4350-09-8
IUPAC Name2-amino-3-(5-hydroxy-1H-indol-3-yl)propanoic acid
Traditional NameDL-5-hydroxytryptophan
SMILESNC(CC1=CNC2=C1C=C(O)C=C2)C(O)=O
InChI IdentifierInChI=1/C11H12N2O3/c12-9(11(15)16)3-6-5-13-10-2-1-7(14)4-8(6)10/h1-2,4-5,9,13-14H,3,12H2,(H,15,16)
InChI KeyInChIKey=LDCYZAJDBXYCGN-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as serotonins. Serotonins are compounds containing a serotonin moiety, which consists of an indole that bears an aminoethyl a position 2 and a hydroxyl group at position 5.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassTryptamines and derivatives
Direct ParentSerotonins
Alternative Parents
Substituents
  • Serotonin
  • Indolyl carboxylic acid derivative
  • Alpha-amino acid
  • Alpha-amino acid or derivatives
  • Hydroxyindole
  • 3-alkylindole
  • Indole
  • 1-hydroxy-2-unsubstituted benzenoid
  • Aralkylamine
  • Substituted pyrrole
  • Benzenoid
  • Pyrrole
  • Heteroaromatic compound
  • Amino acid
  • Amino acid or derivatives
  • Azacycle
  • Carboxylic acid derivative
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Primary aliphatic amine
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Primary amine
  • Carbonyl group
  • Organic nitrogen compound
  • Amine
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Blood
  • Brain
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Tryptophan MetabolismSMP00063 map00380
Aromatic L-Aminoacid Decarboxylase DeficiencySMP00170 Not Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point295-297°C
Boiling PointNot Available
SolubilityNot Available
LogP-2.051
Predicted Properties
PropertyValueSource
Water Solubility3.63 g/LALOGPS
logP-1.6ALOGPS
logP-1.4ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)2.15ChemAxon
pKa (Strongest Basic)9.18ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area99.34 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity58.18 m³·mol⁻¹ChemAxon
Polarizability22.03 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0006-0390000000-3c19ae217ad78448c30f2017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0097-5920000000-eb294b94875b74adc6f82017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00dl-9067000000-2ab7fbf926f4f1b430022017-10-06View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-00di-0090000000-823f10e31a9f155882332012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-053r-0900000000-d763102ca4968c158d292012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-053r-0900000000-500716cec2e9f8383df72012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , negativesplash10-00rx-2930000000-9e9f041cf524d559b3312017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0090000000-44c37ec15a5546b1c3532017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03di-0910000000-5e6f9e21dd30ec8c20f32017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0900000000-b656dc85b8aff47fea962017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-3900000000-94c7412dbb7cb04c9f322017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0w29-0790000000-233a5164a2a4514e5bb92017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0fi0-0980000000-52f402588d34f0e4bf812017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-0910000000-f2841345d00a265d41042017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014j-0900000000-df31c7e703c994b797fe2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-2090000000-28b52756bfbd372bccf42017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-9460000000-093dd610b11a147c20562017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00e9-9500000000-d567d2ab0b6a5e8a8a222017-09-01View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of Toxicity5-Hydroxy-L-tryptophan is the immediate precursor of the neurotransmitter serotonin. An accumulation of 5-hydroxy-L-tryptophan in cerebrospinal fluid occurs in aromatic L-amino acid decarboxylase deficiency, accompanied by an increased excretion in the urine of the patients, which are indicative of the disorder. 5-Hydroxy-L-tryptophan easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. Supplementation with 5-hydroxy-L-tryptophan is hypothesized to normalize serotonin synthesis, which is putatively related to its antidepressant properties.
Metabolism5-Hydroxytryptophan is decarboxylated to serotonin (5-hydroxytryptamine or 5-HT) by the enzyme aromatic-L-amino-acid decarboxylase with the help of vitamin B6. This reaction occurs both in nervous tissue and in the liver.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor use as an antidepressant, appetite suppressant, and sleep aid.
Minimum Risk LevelNot Available
Health EffectsChronically high levels of 5-hydroxytryptophan are associated with Aromatic L-Amino acid Decarboxylase Deficiency.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB02959
HMDB IDHMDB00472
PubChem Compound ID144
ChEMBL IDCHEMBL350221
ChemSpider ID141
KEGG IDC00643
UniProt IDNot Available
OMIM ID
ChEBI ID17780
BioCyc ID5-HYDROXY-TRYPTOPHAN
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia Link5-Hydroxytryptophan
References
Synthesis Reference

British Patent 845,034.

MSDSLink
General References
  1. Iacono RP, Kuniyoshi SM, Ahlman JR, Zimmerman GJ, Maeda G, Pearlstein RD: Concentrations of indoleamine metabolic intermediates in the ventricular cerebrospinal fluid of advanced Parkinson's patients with severe postural instability and gait disorders. J Neural Transm. 1997;104(4-5):451-9. [9295177 ]
  2. Verbeek MM, Geurtz PB, Willemsen MA, Wevers RA: Aromatic L-amino acid decarboxylase enzyme activity in deficient patients and heterozygotes. Mol Genet Metab. 2007 Apr;90(4):363-9. Epub 2007 Jan 19. [17240182 ]
  3. Turner EH, Loftis JM, Blackwell AD: Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006 Mar;109(3):325-38. Epub 2005 Jul 14. [16023217 ]
  4. Turner EH, Blackwell AD: 5-Hydroxytryptophan plus SSRIs for interferon-induced depression: synergistic mechanisms for normalizing synaptic serotonin. Med Hypotheses. 2005;65(1):138-44. [15893130 ]
  5. Shaw K, Turner J, Del Mar C: Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198. [11869656 ]
  6. Rahman MK, Nagatsu T, Sakurai T, Hori S, Abe M, Matsuda M: Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats. Jpn J Pharmacol. 1982 Oct;32(5):803-11. [6983619 ]
  7. Nakatani Y, Sato-Suzuki I, Tsujino N, Nakasato A, Seki Y, Fumoto M, Arita H: Augmented brain 5-HT crosses the blood-brain barrier through the 5-HT transporter in rat. Eur J Neurosci. 2008 May;27(9):2466-72. doi: 10.1111/j.1460-9568.2008.06201.x. [18445233 ]
  8. Bouchard S, Roberge AG: Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat. Can J Biochem. 1979 Jul;57(7):1014-8. [39668 ]
  9. Amamoto T, Sarai K: On the tryptophan-serotonin metabolism in manic-depressive disorders. Changes in plasma 5-HT and 5-HIAA levels and urinary 5-HIAA excretion following oral loading of L-5HTP in patients with depression. Hiroshima J Med Sci. 1976 Sep;25(2-3):135-40. [1088369 ]
  10. Magnussen I, Jensen TS, Rand JH, Van Woert MH: Plasma accumulation of metabolism of orally administered single dose L-5-hydroxytryptophan in man. Acta Pharmacol Toxicol (Copenh). 1981 Sep;49(3):184-9. [6175178 ]
  11. Birdsall TC: 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-80. [9727088 ]
  12. Sternberg EM, Van Woert MH, Young SN, Magnussen I, Baker H, Gauthier S, Osterland CK: Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. N Engl J Med. 1980 Oct 2;303(14):782-7. [6997735 ]
  13. Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V: Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. J Int Med Res. 1990 May-Jun;18(3):201-9. [2193835 ]
  14. Trouillas P, Serratrice G, Laplane D, Rascol A, Augustin P, Barroche G, Clanet M, Degos CF, Desnuelle C, Dumas R, et al.: Levorotatory form of 5-hydroxytryptophan in Friedreich's ataxia. Results of a double-blind drug-placebo cooperative study. Arch Neurol. 1995 May;52(5):456-60. [7733839 ]
  15. De Benedittis G, Massei R: Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. J Neurosurg Sci. 1985 Jul-Sep;29(3):239-48. [3913752 ]
  16. Magnussen I, Van Woert MH: Human pharmacokinetics of long term 5-hydroxytryptophan combined with decarboxylase inhibitors. Eur J Clin Pharmacol. 1982;23(1):81-6. [6182005 ]
  17. Li Kam Wa TC, Freestone S, Samson RR, Johnson NR, Lee MR: A comparison of the renal and neuroendocrine effects of two 5-hydroxytryptamine renal prodrugs in normal man. Clin Sci (Lond). 1993 Nov;85(5):607-14. [8287650 ]
  18. Li Kam Wa TC, Freestone S, Samson RR, Johnston NR, Lee MR: Renal metabolism and effects of the glutamyl derivatives of L-dopa and 5-hydroxytryptophan in man. Clin Sci (Lond). 1996 Aug;91(2):177-85. [8795441 ]
  19. 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. doi: 10.1038/nature07762. [19212411 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Aromatic-L-amino-acid decarboxylase
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
Gene Name:
DDC
Uniprot ID:
P20711
Molecular Weight:
53925.815 Da