You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-05-29 19:26:56 UTC
HMDB IDHMDB00472
Secondary Accession Numbers
  • HMDB00504
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 (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. Confirmation of the diagnosis AADC deficiency is then required by enzyme activity measurement or genetic analysis. 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. (EC 1.13.11.11, TDO). 5-Hydroxy-L-tryptophan has been used clinically for over 30 years. In addition to 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 ).
Structure
Thumb
Synonyms
  1. (+-)-5-Hydroxytryptophan
  2. (S)-5-Hydroxytryptophan
  3. 5-Hydroxy-L-Tryptophan
  4. 5-Hydroxy-tryptophan
  5. 5-Hydroxyl-L-tryptophan
  6. 5-Hydroxytryptophan
  7. 5-Hydroxytryptophan L form
  8. 5-Hydroxytryptophan L-form
  9. Cincofarm
  10. Hydroxytryptophan
  11. L-5-Hydroxytryptophan
  12. Levothym
  13. Levotinine
  14. Oxitriptan
  15. Oxyfan
  16. Oxytryptophan
  17. Pretonine
  18. Quietim
  19. Serotonyl
  20. Telesol
  21. Triptene
Chemical FormulaC11H12N2O3
Average Molecular Weight220.2246
Monoisotopic Molecular Weight220.08479226
IUPAC Name2-amino-3-(5-hydroxy-1H-indol-3-yl)propanoic acid
Traditional Name(+-)-5-hydroxytryptophan
CAS Registry Number4350-09-8
SMILES
NC(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)
InChI KeyLDCYZAJDBXYCGN-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAmino Acids, Peptides, and Analogues
ClassAmino Acids and Derivatives
Sub ClassAlpha Amino Acids and Derivatives
Other Descriptors
  • Aromatic Heteropolycyclic Compounds
  • amino acid zwitterion(ChEBI)
Substituents
  • Carboxylic Acid
  • Indole
  • Indolyl Carboxylic Acid Derivative
  • Phenol
  • Phenol Derivative
  • Primary Aliphatic Amine (Alkylamine)
  • Pyrrole
  • Serotonin
  • Tryptamine
Direct ParentAlpha Amino Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Protein synthesis, amino acid biosynthesis
ApplicationNot Available
Cellular locations
  • Cytoplasm
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 Area99.34ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity58.18ChemAxon
Polarizability22.03ChemAxon
Spectra
SpectraMS/MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Tryptophan MetabolismSMP00063map00380
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
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
UrineDetected and Quantified0.0078 umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB02959
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB006231
KNApSAcK IDC00001371
Chemspider ID141
KEGG Compound IDC01017
BioCyc ID5-HYDROXY-TRYPTOPHAN
BiGG ID36630
Wikipedia Link5-HTP
NuGOwiki LinkHMDB00472
Metagene LinkHMDB00472
METLIN IDNot Available
PubChem Compound144
PDB IDNot Available
ChEBI ID28171
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. 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. 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. Birdsall TC: 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-80. Pubmed: 9727088
  18. Shaw K, Turner J, Del Mar C: Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198. Pubmed: 11869656
  19. 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
  20. 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