Human Metabolome Database Version 3.5

Showing metabocard for 5-Hydroxy-L-tryptophan (HMDB00472)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-05-29 13:26:56 -0600
HMDB ID HMDB00472
Secondary Accession Numbers
  • HMDB00504
Metabolite Identification
Common Name 5-Hydroxy-L-tryptophan
Description 5-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 Link_out), 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 Link_out, 17240182 Link_out, 16023217 Link_out).
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
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 Formula C11H12N2O3
Average Molecular Weight 220.2246
Monoisotopic Molecular Weight 220.08479226
IUPAC Name 2-amino-3-(5-hydroxy-1H-indol-3-yl)propanoic acid
Traditional IUPAC Name (+-)-5-hydroxytryptophan
CAS Registry Number 4350-09-8
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 Key LDCYZAJDBXYCGN-UHFFFAOYSA-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
  • 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 Parent Alpha Amino Acids and Derivatives
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction
  • Protein synthesis, amino acid biosynthesis
Application Not Available
Cellular locations
  • Cytoplasm
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 293 - 298 °C Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP -2.051 Not Available
Predicted Properties
Property Value Source
Water Solubility 3.63 g/L ALOGPS
LogP -1.56 ALOGPS
LogP -1.4 ChemAxon
LogS -1.78 ALOGPS
pKa (strongest acidic) 2.15 ChemAxon
pKa (strongest basic) 9.18 ChemAxon
Hydrogen Acceptor Count 4 ChemAxon
Hydrogen Donor Count 4 ChemAxon
Polar Surface Area 99.34 A2 ChemAxon
Rotatable Bond Count 3 ChemAxon
Refractivity 58.18 ChemAxon
Polarizability 22.03 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge 0 ChemAxon
Spectra
1H NMR Spectrum
MS/MS Spectrum Quattro_QQQ 10
MS/MS Spectrum Quattro_QQQ 25
MS/MS Spectrum Quattro_QQQ 40
[1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Prostate
Pathways
Name SMPDB Link KEGG Link
Tryptophan Metabolism SMP00063 map00380 Link_out
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
0.018 +/- 0.0027 uM Adult (>18 years old) Both Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
0.005 (0.00-0.010) uM Infant (0-1 year old) Both Normal
Urine Detected and Quantified
0.0078 umol/mmol creatinine Adult (>18 years old) Both Normal
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease References None
Associated OMIM IDs None
DrugBank ID DB02959 Link_out
DrugBank Metabolite ID Not Available
Phenol Explorer Compound ID Not Available
Phenol Explorer Metabolite ID Not Available
FoodDB ID FDB006231
KNApSAcK ID C00001371 Link_out
Chemspider ID 141 Link_out
KEGG Compound ID C01017 Link_out
BioCyc ID 5-HYDROXY-TRYPTOPHAN Link_out
BiGG ID 36630 Link_out
Wikipedia Link 5-HTP Link_out
NuGOwiki Link HMDB00472 Link_out
Metagene Link HMDB00472 Link_out
METLIN ID Not Available
PubChem Compound 144 Link_out
PDB ID Not Available
ChEBI ID 28171 Link_out
References
Synthesis Reference Boroda, 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. 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 Link_out
  2. 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 Link_out
  3. 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 Link_out
  4. 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 Link_out
  5. 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 Link_out
  6. 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 Link_out
  7. 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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  16. Birdsall TC: 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-80. Pubmed: 9727088 Link_out
  17. Birdsall TC: 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-80. Pubmed: 9727088 Link_out
  18. Shaw K, Turner J, Del Mar C: Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198. Pubmed: 11869656 Link_out
  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 Link_out
  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 Link_out

Enzymes
Name: Aromatic-L-amino-acid decarboxylase
Reactions: Not Available
Gene Name: DDC
Uniprot ID: P20711 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Indoleamine 2,3-dioxygenase 1
Reactions: Not Available
Gene Name: IDO1
Uniprot ID: P14902 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Tryptophan 5-hydroxylase 1
Reactions: Not Available
Gene Name: TPH1
Uniprot ID: P17752 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Tryptophan 5-hydroxylase 2
Reactions: Not Available
Gene Name: TPH2
Uniprot ID: Q8IWU9 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Indoleamine 2,3-dioxygenase 2
Reactions: Not Available
Gene Name: IDO2
Uniprot ID: Q6ZQW0 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA