MiMeDB: Showing metabocard for 5-Hydroxy-L-tryptophan (MMDBc0047911)

Not Available

Record Information

Version

1.0

Status

Detected and Quantified

Creation Date

2021-11-23 23:14:34 UTC

Update Date

2024-10-13 06:39:16 UTC

Metabolite ID

MMDBc0047911

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 (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

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
5-Hydroxytryptophan L-form	ChEBI
Cincofarm	ChEBI
L-5-Hydroxytryptophan	ChEBI
Levothym	ChEBI
Oxitriptan	ChEBI
Tript-OH	ChEBI
Hydroxy-5 L-tryptophane	HMDB
5-HTP	HMDB
Hydroxytryptophan	HMDB
5-Hydroxytryptophan	HMDB
5 Hydroxytryptophan	HMDB
5-Hydroxy- tryptophan	HMDB
Oxytryptophan	HMDB
Tryptophan, 5 hydroxy	HMDB
(S)-5-Hydroxytryptophan	HMDB
5-Hydroxyl-L-tryptophan	HMDB
Levotonine	HMDB
Oxyfan	HMDB
Pretonine	HMDB
Quietim	HMDB
Serotonyl	HMDB
Telesol	HMDB
Triptene	HMDB
Triptum	HMDB
L-5-HTP	HMDB
5-Hydroxy-L-tryptophan	HMDB

Molecular Formula

C₁₁H₁₂N₂O₃

Average Mass

220.2246

Monoisotopic Mass

220.08479226

IUPAC Name

Not Available

Traditional Name

Not Available

CAS Registry Number

4350-09-8

SMILES

Not Available

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 Key

LDCYZAJDBXYCGN-VIFPVBQESA-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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Indoles and derivatives

Sub Class

Tryptamines and derivatives

Direct Parent

Serotonins

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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

non-proteinogenic L-alpha-amino acid (CHEBI:17780 )
5-hydroxytryptophan (CHEBI:17780 )
hydroxy-L-tryptophan (CHEBI:17780 )

Functional Ontology

Not Available

Physical Properties

State

Solid

Predicted Properties

Not Available

Spectra

Not Available

Biological Properties

Cellular Locations

Cytoplasm

Biospecimen Locations

Blood
Cerebrospinal Fluid (CSF)
Feces
Prostate
Urine

Tissue Locations

Prostate

Associated OMIM IDs

114500 (Colorectal cancer)
610247 (Eosinophilic esophagitis)

Human Proteins and Enzymes

Protein ID	Protein Name	Protein Type	Uniprot ID	Species
MMDBp0191948	Aromatic-L-amino-acid decarboxylase	Enzyme	P20711	Homo sapiens
MMDBp0192103	Indoleamine 2,3-dioxygenase 1	Unknown	P14902	Homo sapiens
MMDBp0192127	Tryptophan 5-hydroxylase 1	Enzyme	P17752	Homo sapiens
MMDBp0192129	Tryptophan 5-hydroxylase 2	Enzyme	Q8IWU9	Homo sapiens
MMDBp0193303	Aryl hydrocarbon receptor	Unknown	P35869	Homo sapiens
MMDBp0194191	Indoleamine 2,3-dioxygenase 2	Unknown	Q6ZQW0	Homo sapiens

Human Pathways

Pathways

Name	SMPDB/PathBank

Metabolic Reactions

Reactions

Reaction ID	Precursor	Product	Enzyme	Data Source	Reference
MMDBr0000114	5-Hydroxy-L-tryptophan	Serotonin	Not Available	VMH	1540578
MMDBr0000119	5-Hydroxy-L-tryptophan	5-Hydroxy-N-formylkynurenine	indoleamine 2,3-dioxygenase 1	VMH	10564724
MMDBr0002276	L-erythro-tetrahydrobiopterin	5-Hydroxy-L-tryptophan	tryptophan hydroxylase 1	VMH	10727395 12379098
MMDBr0002541	L-erythro-tetrahydrobiopterin	5-Hydroxy-L-tryptophan	tryptophan hydroxylase 1	VMH	30371894

Health Effects and Bioactivity

Health Outcome/Bioactivity	Metabolite Response/Effect	Evidence Type	Host and Biospecimen	Data Source	Reference
Aromatic l-amino acid decarboxylase deficiency		Association	Human Cerebrospinal Fluid (CSF)	HMDB	9686366

Microbial Sources

Superkingdom/Kingdom	Phylum	Total species	Hosts and Body Sites	Microbial Links
Bacteria	Firmicutes	89	Human feces; Pig ; Human ; Cattle	Metabolic reconstruction
Bacteria	Proteobacteria	207	Human feces; Human sputum; Human ; Human unknown; Pig ; Human pleural fluid plaque; Human dental plaque; Human nasal swab	Metabolic reconstruction
Bacteria	Actinobacteria	86	Human feces; Human ; Human supragingival plaque	Metabolic reconstruction
Bacteria	Bacteroidetes	6	Human feces	Metabolic reconstruction
Archaea	Euryarchaeota	2		Metabolic reconstruction
Bacteria	Fusobacteria	2	Human ; Human feces	Metabolic reconstruction
Bacteria	Planctomycetes	2	Human feces	Metabolic reconstruction

Exposure Sources

Source Type	Source Sub-type	Species	Data Source	Reference
Animal	Milk	Bos taurus	FooDB	28342601
Plant	Plant	Musa x paradisiaca	FooDB	DUKE

Source Type	Activity	Data Source	Reference
Drugs	Antimicrobial	U.S. Environmental Protection Agency	CompTox
Cosmetics	Not Available	U.S. Environmental Protection Agency	CompTox
Domestics	Not Available	U.S. Environmental Protection Agency	CompTox

Host Biospecimen and Location

Host and Biospecimen	Status	Mean	Std	Min	Max	Units	Age	Sex	Health Condition	Data Source	Reference
Human Feces	Detected but not Quantified									HMDB
Human Cerebrospinal fluid (csf)	Detected and Quantified	0.063				uM	Infant (0-1 year old)	Female	Aromatic L-amino acid decarboxylase deficiency	HMDB	9686366
Human Cerebrospinal fluid (csf)	Detected and Quantified			0.0970	0.136	uM	Children (1-13 years old)	Female	Aromatic L-amino acid decarboxylase deficiency	HMDB	9686366
Human Urine	Detected and Quantified	0.0078				umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	19309105
Human Cerebrospinal fluid (csf)	Detected and Quantified	<0.0100				uM	Children (1-13 years old)	Female	Normal	HMDB	9686366
Human Cerebrospinal fluid (csf)	Detected and Quantified	0.005		0.00	0.010	uM	Infant (0-1 year old)	Both	Normal	HMDB	11486900
Human Blood	Detected and Quantified	0.018	0.0027			uM	Adult (>18 years old)	Both	Normal	HMDB	11910264
Human Prostate	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Urine	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057
Human Blood	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057

External Links

HMDB ID

HMDB0000472

DrugBank ID

DB02959

Phenol Explorer Compound ID

Not Available

FooDB ID

KNApSAcK ID

Chemspider ID

KEGG Compound ID

BioCyc ID

BiGG ID

Not Available

Wikipedia Link

5-Hydroxytryptophan

METLIN ID

Not Available

PubChem Compound

439280

PDB ID

Not Available

ChEBI ID

17780

Food Biomarker Ontology

Not Available

References

Synthesis Reference

Not Available

General References

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. doi: 10.1139/o79-126. [PubMed:39668 ]
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 ]
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. doi: 10.1177/030006059001800304. [PubMed:2193835 ]
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 ]
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. doi: 10.1111/j.1600-0773.1981.tb00890.x. [PubMed:6175178 ]
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. doi: 10.1007/BF01061381. [PubMed:6182005 ]
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. doi: 10.1254/jjp.32.803. [PubMed:6983619 ]
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. doi: 10.1056/NEJM198010023031403. [PubMed:6997735 ]
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. doi: 10.1001/archneur.1995.00540290042016. [PubMed:7733839 ]
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. doi: 10.1042/cs0850607. [PubMed:8287650 ]
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. doi: 10.1042/cs0910177. [PubMed:8795441 ]
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. doi: 10.1007/BF01277663. [PubMed:9295177 ]
Birdsall TC: 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-80. [PubMed:9727088 ]
Shaw K, Turner J, Del Mar C: Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198. doi: 10.1002/14651858.CD003198. [PubMed:11869656 ]
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. doi: 10.1016/j.mehy.2005.01.026. [PubMed:15893130 ]
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. doi: 10.1016/j.pharmthera.2005.06.004. Epub 2005 Jul 14. [PubMed:16023217 ]
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. doi: 10.1016/j.ymgme.2006.12.001. Epub 2007 Jan 19. [PubMed:17240182 ]
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 ]
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 ]

Showing metabocard for 5-Hydroxy-L-tryptophan (MMDBc0047911)

MOL for #<Metabolite:0x00007fdb3b480c38>

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Structure for #<Metabolite:0x00007fdb3b480c38>

3D Structure for #<Metabolite:0x00007fdb3b480c38>