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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2018-02-27 18:30:55 UTC
HMDB IDHMDB0000472
Secondary Accession Numbers
  • HMDB0000504
  • HMDB0015571
  • HMDB00472
  • HMDB00504
  • HMDB15571
Metabolite Identification
Common Name5-Hydroxy-L-tryptophan
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.
Structure
Thumb
Synonyms
ValueSource
5-Hydroxytryptophan L-formChEBI
CincofarmChEBI
L-5-HydroxytryptophanChEBI
LevothymChEBI
Tript-OHChEBI
5-Hydroxy-L-tryptophanHMDB
Hydroxy-5 L-tryptophaneHMDB
5-HTPMeSH
HydroxytryptophanMeSH
5-HydroxytryptophanMeSH
5 HydroxytryptophanMeSH
5-Hydroxy- tryptophanMeSH
OxytryptophanMeSH
Tryptophan, 5 hydroxyMeSH
(S)-5-HydroxytryptophanHMDB
5-Hydroxyl-L-tryptophanHMDB
LevotonineHMDB
OxyfanHMDB
OxitriptanHMDB
PretonineHMDB
QuietimHMDB
SerotonylHMDB
TelesolHMDB
TripteneHMDB
TriptumHMDB
L-5-HTPCAS
Chemical FormulaC11H12N2O3
Average Molecular Weight220.2246
Monoisotopic Molecular Weight220.08479226
IUPAC Name(2S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propanoic acid
Traditional Namehydroxytryptophan
CAS Registry Number4350-09-8
SMILES
N[C@@H](CC1=CNC2=C1C=C(O)C=C2)C(O)=O
InChI Identifier
InChI=1S/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)/t9-/m0/s1
InChI KeyLDCYZAJDBXYCGN-VIFPVBQESA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as serotonins. These 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
  • 3-alkylindole
  • L-alpha-amino acid
  • Hydroxyindole
  • Indole
  • Aralkylamine
  • 1-hydroxy-2-unsubstituted benzenoid
  • Benzenoid
  • Substituted pyrrole
  • Heteroaromatic compound
  • Pyrrole
  • Amino acid
  • Amino acid or derivatives
  • Azacycle
  • Carboxylic acid derivative
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Primary aliphatic amine
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Primary amine
  • Carbonyl group
  • Organopnictogen compound
  • Amine
  • Organic oxide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Indirect biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point293 - 298 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP-2.051Not Available
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 Key
GC-MSGC-MS Spectrum - GC-MS (4 TMS)splash10-0006-0390000000-d4e36a90b7591787e67bView in MoNA
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-0006-1390000000-b0af49def87c0211653cView in MoNA
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-014i-0390000000-8b7f6cc8f51c032dd86dView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-014i-0390000000-88191cf8140abf0f3205View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0006-0290000000-a30ea02ff8d4d14ba7a4View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0006-0390000000-d4e36a90b7591787e67bView in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0006-1390000000-b0af49def87c0211653cView in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-014i-0390000000-8b7f6cc8f51c032dd86dView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00bd-4920000000-c1f07beecfc6ada179c1View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00di-9044000000-9dc0e361e3885451d81fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0790000000-a699ed429ebd1609f995View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03e9-0900000000-bbd302f8ff188f6cf93dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-053r-0900000000-6cc3ba396b1cfa8db1e6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-053r-2900000000-90a465428eacaced71e2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00b9-0950000000-e3f9fbda111b2109f630View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-0900000000-b21f3fecc8ae15c125deView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0002-0900000000-817e4d468ea1bf1a3bc3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-2190000000-65b1ee730ae09a2cd6a5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-9650000000-68d73bfc7c9dd0f880e1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00di-9600000000-c58badf19c5cbb2f4347View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Urine
Tissue Location
  • Prostate
Pathways
NameSMPDB/PathwhizKEGG
Tryptophan MetabolismThumbThumb?image type=greyscaleThumb?image type=simpleMap00380
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.018 +/- 0.0027 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.005 (0.00-0.010) uMInfant (0-1 year old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified<0.0100 uMChildren (1-13 years old)Female
Normal
details
UrineDetected and Quantified0.0078 umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
Cerebrospinal Fluid (CSF)Detected and Quantified0.063 uMInfant (0-1 year old)Female
Aromatic L-amino acid decarboxylase deficiency
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0970-0.136 uMChildren (1-13 years old)Female
Aromatic L-amino acid decarboxylase deficiency
details
FecesDetected but not Quantified Children (6 - 18 years old)BothCrohns disease details
FecesDetected but not Quantified Children (6 - 18 years old)BothUlcerative colitis details
FecesDetected but not Quantified Children (6 - 18 years old)Bothenthesitis-related arthritis details
FecesDetected but not Quantified Children (6 - 18 years old)Not SpecifiedCrohns disease details
FecesDetected but not Quantified Children (6 - 18 years old)Not SpecifiedUlcerative colitis details
FecesDetected but not Quantified Children (6 - 18 years old)Not SpecifiedUlcerative colitis details
UrineDetected but not Quantified Adult (>18 years old)BothColorectal cancer details
Associated Disorders and Diseases
Disease References
Aromatic L-amino acid decarboxylase deficiency
  1. Abeling NG, van Gennip AH, Barth PG, van Cruchten A, Westra M, Wijburg FA: Aromatic L-amino acid decarboxylase deficiency: a new case with a mild clinical presentation and unexpected laboratory findings. J Inherit Metab Dis. 1998 Jun;21(3):240-2. [PubMed:9686366 ]
Associated OMIM IDs
  • 608643 (Aromatic L-amino acid decarboxylase deficiency)
DrugBank IDDB02959
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDC00001371
Chemspider ID388413
KEGG Compound IDC00643
BioCyc ID5-HYDROXY-TRYPTOPHAN
BiGG IDNot Available
Wikipedia Link5-Hydroxytryptophan
METLIN IDNot Available
PubChem Compound439280
PDB IDNot Available
ChEBI ID17780
References
Synthesis ReferenceBoroda, E.; Rakowska, S.; Kanski, R.; Kanska, M. Enzymatic synthesis of L-tryptophan and 5'-hydroxy-L-tryptophan labeled with deuterium and tritium at the a-carbon position. Journal of Labelled Compounds & Radiopharmaceuticals (2003), 46(8), 691-698.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. 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. [PubMed:19212411 ]
  2. 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. [PubMed:6182005 ]
  3. 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. [PubMed:8287650 ]
  4. 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. [PubMed:8795441 ]
  5. 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 (Vienna). 1997;104(4-5):451-9. [PubMed:9295177 ]
  6. 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. [PubMed:17240182 ]
  7. 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. [PubMed:16023217 ]
  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. [PubMed: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. [PubMed:1088369 ]
  10. 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. [PubMed:2193835 ]
  11. 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. [PubMed:3913752 ]
  12. 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. [PubMed:6175178 ]
  13. 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. [PubMed:6983619 ]
  14. 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. [PubMed:6997735 ]
  15. 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. [PubMed:7733839 ]
  16. Birdsall TC: 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-80. [PubMed:9727088 ]
  17. Shaw K, Turner J, Del Mar C: Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198. [PubMed:11869656 ]
  18. 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. [PubMed:15893130 ]
  19. 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. [PubMed:18445233 ]

Enzymes

General function:
Involved in carboxy-lyase activity
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:
53893.755
General function:
Involved in heme binding
Specific function:
Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen.
Gene Name:
IDO1
Uniprot ID:
P14902
Molecular weight:
45325.89
General function:
Involved in amino acid binding
Specific function:
Not Available
Gene Name:
TPH1
Uniprot ID:
P17752
Molecular weight:
50984.725
General function:
Involved in amino acid binding
Specific function:
Not Available
Gene Name:
TPH2
Uniprot ID:
Q8IWU9
Molecular weight:
56056.295
General function:
Involved in heme binding
Specific function:
Catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan catabolism.
Gene Name:
IDO2
Uniprot ID:
Q6ZQW0
Molecular weight:
47074.745