Tryptophan metabolism (Homo sapiens)

From WikiPathways

Revision as of 14:12, 3 June 2022 by DeSl (Talk | contribs)
Jump to: navigation, search
3-665, 666655, 6655556565 Enterochromaffin CellCinnavalininateIndole-3-acetateendogenous serotonin in the gut is mainly released from ECs in response to a number of metabolites:Protein found in differentspecies, leading to individualUniProt annotations.SerotoninFormyl-N-acetyl-5-methoxykynurenamine2-Aminomuconate3-Hydroxy-L-kynurenineNAD+ and niacin production5-hydroxykynurenamine2-Amino-3-carboxymuconateFormyl-5-hydroxykynurenamineLEGENDQuinolinate5-MethoxyindoleacetateIndole-3-acetaldehydemicrobial pathway interaction4,8-DihydroxyquinolineUnclear which route is takento produce indolyl acryloyl glycine.(S)-3-Hydroxybutyryl-CoA3-Hydroxyanthranilate2-Oxoadipate3-HydroxykynurenamineN-formylanthranilate5-HydroxyindoleacetateAnthranilateAhR ligandPMID:31258331.2-Aminomuconate65, 6665, 65, 66, 85Kynurenic AcidButyrateACMSDAcetyl-CoAINMTTMOECHS1SCFAsTDO25-HydroxykynurenineMAOAindole-sulfonic acidCATTryptopholIndicanN-AcetylserotoninAcetoacetyl-CoAIDO1Glycolysis/GluconeogenesisTyramineHAAOALDH2DDCL-KynurenineTrDAFMID4,6-DihydroxyquinolineKYAT1KMOIndole-3-acetamideGlutaryl-CoAKYNUHDACMAOAIDO21.5.1.-STAT1TpH1skatoleN-MethyltryptaminecholateINDO2AANATTNADDCN-MethylserotoninNicotinate and nicotinamide metabolismIndole-3-aldehydeBenzoate degradation via hydroxylationPhenylalanine, Tyrosine and Tryptophan metabolismTPH2MelatoninKYNUDLDCYP1A16-HydroxymelatoninTryptamineIndolyl acryloyl glycineMAOAIDO2IL4I1DDC5-Hydroxy-N-formylkynurenineMAOAAHRAOX1ASMTINMTALDH8A1ILAIndole4.1.1.-ALDH2AOC1GCDHCrotonoyl-CoA4-(2-Amino-3-hydroxyphenyl)-2,4-dioxobutanoateFormylkynurenineIndolepyruvateArATASMTfldHACAT1IDO1alpha-tocopherolAADAT4-aminobenzoic acid5-Hydroxy-L-tryptophan5-HydroxyindoleacetaldehydeXanthurenic acidL-Tryptophan655666559166, 85102, 5665565IDO25AFMIDKYNUpicolinate6HADHIDO266Potential AhR ligand(but in supraphysiological concentrations)IA6IPA6666porCporB11acdAfldHfldBfldCacdATNATNATNA6Quinaldic Acid6KYAT21KYAT3KYAT41166Indole acetic glutamine66, 865AhR ligandPMID:31825083.AHRAHRAHRIDO1IDO2105STAT1STAT1PSCFAs77777


Description

This pathway describes the metabolism of tryptophan, an essential amino acid.

Originally adapted from: KEGG, and expanded with information from Agus 2018, Dehhaghi 2019, and Gao 2020.

"The tryptophan (Trp) metabolism follows three major pathways in the gastrointestinal tract: 1. direct transformation of Trp, including ligands of the aryl hydrocarbon receptor (AhR), by the gut microbiota; 2. through the kynurenine pathway in both immune and epithelial cells via indoleamine 2,3-dioxygenase (IDO) 1; 3. the serotonin (5-hydroxytryptamine [5-HT]) production pathway in enterochromaffin cells via Trp hydroxylase 1 (TpH1)." Agus 2018.


Proteins on this pathway have targeted assays available via the CPTAC Assay Portal.

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Qian Han, Tao Cai, Danilo A. Tagle, Jianyong Li; ''Structure, expression, and function of kynurenine aminotransferases in human and rodent brains''; Cell Mol Life Sci., 2010 PubMed Europe PMC Scholia
  2. Jessica M Yano, Kristie Yu, Gregory P Donaldson, Gauri G Shastri, Phoebe Ann, Liang Ma, Cathryn R Nagler, Rustem F Ismagilov, Sarkis K Mazmanian, Elaine Y Hsiao; ''Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis''; Cell, 2015 PubMed Europe PMC Scholia
  3. Allison Agus, Julien Planchais, Harry Sokol 2; ''Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease''; Cell Host Microbe, 2018 PubMed Europe PMC Scholia
  4. ''''; https://www.genome.jp/dbget-bin/www_bget?pathway+rno00380,
  5. Kan Gao, Chun-Long Mu, Aitak Farzi, Wei-Yun Zhu; ''Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain''; Adv Nutr ., 2020 PubMed Europe PMC Scholia
  6. Mona Dehhaghi, Hamed Kazemi Shariat Panahi, Gilles J Guillemin; ''Microorganisms, Tryptophan Metabolism, and Kynurenine Pathway: A Complex Interconnected Loop Influencing Human Health Status''; Int J Tryptophan Res., 2019 PubMed Europe PMC Scholia
  7. Gary M Mawe, Jill M Hoffman; ''Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets''; Nat Rev Gastroenterol Hepatol., 2013 PubMed Europe PMC Scholia
  8. Jing Gao, Kang Xu, Hongnan Liu, Gang Liu, Miaomiao Bai, Can Peng, Tiejun Li, Yulong Yin; ''''; , PubMed Europe PMC Scholia
  9. Camille Martin-Gallausiaux, Pierre Larraufie, Anne Jarry, Fabienne Béguet-Crespe, Ludovica Marinelli, Florence Ledue, Frank Reimann, Hervé M Blottière, Nicolas Lapaque; ''Butyrate Produced by Commensal Bacteria Down-Regulates Indolamine 2,3-Dioxygenase 1 ( IDO-1) Expression via a Dual Mechanism in Human Intestinal Epithelial Cells''; Front Immunol., 2018 PubMed Europe PMC Scholia
  10. G Clarke, S Grenham, P Scully, P Fitzgerald, R D Moloney, F Shanahan, T G Dinan, J F Cryan; ''The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner''; Mol Psychiatry, 2013 PubMed Europe PMC Scholia
  11. Denisse Bravo, Anilei Hoare, Cristopher Soto, Manuel A Valenzuela, Andrew Fg Quest; ''Helicobacter pylori in human health and disease: Mechanisms for local gastric and systemic effects''; World J Gastroenterol., 2018 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
122957view14:15, 3 June 2022DeSlOntology Term : 'indoleamine and related compounds metabolic pathway' added !
122956view14:14, 3 June 2022DeSlOntology Term : 'indoleamine and related compounds biosynthetic pathway' added !
122955view14:13, 3 June 2022DeSlOntology Term : 'type EC enteroendocrine cell' added !
122954view14:13, 3 June 2022DeSlOntology Term : 'enterochromaffin-like cell' added !
122953view14:13, 3 June 2022DeSlOntology Term : 'regulatory pathway' added !
122952view14:12, 3 June 2022DeSlOntology Term : 'signaling pathway' added !
122951view14:12, 3 June 2022DeSlOntology Term : 'classic metabolic pathway' added !
122950view14:12, 3 June 2022DeSlOntology Term : 'aryl hydrocarbon receptor signaling pathway' added !
122949view14:12, 3 June 2022DeSlOntology Term : 'serotonin secreting cell' added !
122948view14:12, 3 June 2022DeSlOntology Term : 'kynurenine metabolic pathway' added !
122947view14:11, 3 June 2022DeSlOntology Term : 'tryptophan degradation pathway' added !
122946view14:11, 3 June 2022DeSlOntology Term : 'tryptophan biosynthetic pathway' added !
122945view14:10, 3 June 2022DeSlRemoved unconnected interaction
122944view14:05, 3 June 2022DeSlAdded serotonin stimuli
122943view13:54, 3 June 2022DeSlAdded HDAC regulation of IDO info.
122942view13:43, 3 June 2022DeSlAdded influence of butyrate to kynurenic PW
122941view13:20, 3 June 2022DeSlAdded details from Fig. 1 PMID:31825083
122940view13:09, 3 June 2022DeSlAdded more details from PMID: 31258331, Fig. 3
122939view12:48, 3 June 2022DeSlAdded more details on kynurenine PW
122938view12:30, 3 June 2022DeSlAdded more details from Agus et al to description.
122937view12:27, 3 June 2022DeSlAdded last step of Fig.2
122936view12:19, 3 June 2022DeSlFinalized annotation of INDOLE microbial genes/proteins
122935view11:48, 3 June 2022DeSlAdded more details for legend
122934view11:43, 3 June 2022DeSlAdded more microbial interactions to PW
122933view11:32, 3 June 2022DeSlAdded first microbial pathway interactions
122932view11:11, 3 June 2022DeSlAdded refs to PW
122931view11:06, 3 June 2022DeSlAdded more lit. refs to description
122928view10:07, 3 June 2022DeSlConnected unconnected line
122927view10:06, 3 June 2022DeSlAdded latest missing metabolite IDs.
122926view10:02, 3 June 2022DeSlUpdated last section of PW
122924view09:29, 3 June 2022DeSlChecked bottom part
122922view08:48, 3 June 2022DeSlChecked left middle section
122919view08:18, 3 June 2022DeSlStarting to remove elements not relevant for species.
119262view07:46, 23 June 2021Finterlyadded KEGG pathway info to publicationXref
113999view21:46, 16 December 2020EgonwAnother pathway clickable
106518view23:30, 5 September 2019Khanspersadded reference
106203view12:09, 16 August 2019MaintBotHMDB identifier normalization
105847view23:14, 15 August 2019KhanspersModified description
104898view15:43, 23 June 2019EgonwReplaced secondary ChEBI identifiers with a primary identifiers.
104829view14:28, 19 June 2019Fehrhartadded some more metabolite IDs
104828view14:20, 19 June 2019Fehrhartadded metabolite IDs
104821view12:57, 19 June 2019FehrhartModified description
103977view02:10, 20 April 2019AlexanderPicoFixed EC6.3.2.-
102311view21:09, 17 December 2018KhanspersModified description
102310view21:08, 17 December 2018Khanspersremoved GenMAPP comment
94086view12:40, 18 August 2017DeSlModified description
93713view12:41, 11 August 2017DeSlModified description
85055view10:47, 10 April 2016EgonwReplaced a Wikipedia ID with a ChEBI ID.
79226view18:51, 15 March 2015EgonwAdded a number of missing metabolite Chemspider identifiers (based on IUPAC names).
77387view12:04, 4 September 2014EgonwAdded a number of missing metabolite Chemspider identifiers (based on IUPAC names).

External references

DataNodes

View all...
NameTypeDatabase referenceComment
(S)-3-Hydroxy butyryl-CoAMetaboliteC01144 (KEGG Compound) (S)-3-Hydroxybutanoyl-CoA
1.5.1.-GeneProduct1.5.1.- (Enzyme Nomenclature) Unclear which specific protein acts in this reaction.
2-Amino-3-carboxymuconateMetaboliteC04409 (KEGG Compound) 2-Amino-3-carboxymuconate
2-AminomuconateMetaboliteC02220 (KEGG Compound) 2-Aminomuconate
2-AminomuconateMetaboliteC03824 (KEGG Compound) 2-Aminomuconate
2-OxoadipateMetabolite19951093 (Chemspider) 2-Oxoadipate
3-Hydroxy- L-kynurenineMetaboliteC03227 (KEGG Compound) AKA 3-Hydroxy-L-kynurenine, 3H-KYN
3-HydroxyanthranilateMetabolite7822291 (Chemspider) AKA 3-Hydroxyanthranilate, 3-HAA
3-HydroxykynurenamineMetaboliteHMDB0060281 (HMDB) 3-Hydroxykynurenamine
4,6-DihydroxyquinolineMetaboliteHMDB0004077 (HMDB)
4,8-DihydroxyquinolineMetaboliteCHEBI:28883 (ChEBI) 4,8-Dihydroxyquinoline
4-(2-Amino-3-hydroxyphenyl)- 2,4-dioxobutanoateMetaboliteHMDB0004083 (HMDB)
4-aminobenzoic acidMetaboliteCHEBI:30753 (ChEBI)
4.1.1.-GeneProduct4.1.1.- (Enzyme Nomenclature) Unclear which specific protein acts in this reaction
5-Hydroxy-L-tryptophanMetaboliteHMDB0000472 (HMDB) "The neurotransmitter 5-HT is produced in the brain through the Trp hydroxylase 2 enzyme (TpH2), [...], more than 90% of the body's 5-HT is produced in the gut and particularly in enterochromaffin cells (ECs), a specialized subtype of intestinal epithelial cell."
5-Hydroxy-N-formylkynurenineMetaboliteHMDB0004086 (HMDB)
5-HydroxyindoleacetaldehydeMetaboliteHMDB0004073 (HMDB) AKA 5-HIAA
5-HydroxyindoleacetateMetabolite10637170 (Chemspider) 5-Hydroxyindoleacetate
5-HydroxykynurenineMetabolite484-78-6 (CAS)
5-MethoxyindoleacetateMetabolite14533147 (Chemspider) 5-Methoxyindoleacetate
5-hydroxykynurenamineMetaboliteCHEBI:62214 (ChEBI) 5-Hydroxykynurenamine
6-HydroxymelatoninMetabolite2208-41-5 (CAS)
AADATGeneProduct56267 (Entrez Gene)
AANATGeneProduct15 (Entrez Gene)
ACAT1GeneProduct38 (Entrez Gene)
ACMSDGeneProduct130013 (Entrez Gene)
AFMIDGeneProduct125061 (Entrez Gene)
AHRProteinAHR (HGNC)
ALDH2GeneProduct217 (Entrez Gene)
ALDH2ProteinP05091 (Uniprot-TrEMBL)
ALDH8A1GeneProduct64577 (Entrez Gene)
AOC1GeneProduct26 (Entrez Gene) aka ABP1
AOX1GeneProduct316 (Entrez Gene)
ASMTGeneProduct438 (Entrez Gene)
Acetoacetyl-CoAMetaboliteC00332 (KEGG Compound)
Acetyl-CoAMetabolite72-89-9 (CAS) Acetyl-CoA
AnthranilateMetabolite4573598 (Chemspider) Anthranilate
ArATProtein2.6.1.57 (Enzyme Nomenclature) AKA Aromatic amino acid aminotransferase, group of proteins
Benzoate degradation via hydroxylationPathway
ButyrateMetaboliteCHEBI:17968 (ChEBI)
CATGeneProduct847 (Entrez Gene)
CYP1A1GeneProduct1543 (Entrez Gene)
CinnavalininateMetaboliteC05640 (KEGG Compound) Cinnavalininate
Crotonoyl-CoAMetaboliteC00877 (KEGG Compound)
DDCGeneProduct1644 (Entrez Gene) Known under two EC numbers: aromatic-L-amino-acid/L-tryptophan decarboxylase [EC:4.1.1.28; EC:4.1.1.105]
DLDGeneProduct1738 (Entrez Gene) aka OADH
ECHS1GeneProduct1892 (Entrez Gene)
Formyl-5-hydroxy kynurenamineMetaboliteHMDB0012948 (HMDB)
Formyl-N-acetyl-5- methoxykynurenamineMetaboliteC05642 (KEGG Compound) Formyl-N-acetyl-5-methoxykynurenamine
FormylkynurenineMetabolite1022-31-7 (CAS) Formylkynurenine
GCDHGeneProduct2639 (Entrez Gene) predicted
Glutaryl-CoAMetaboliteC00527 (KEGG Compound)
Glycolysis/GluconeogenesisPathwayWP534 (WikiPathways)
HAAOGeneProduct23498 (Entrez Gene) AKA 3-hydroxyanthraniate 3,4-dioxygenase
HADHProteinQ16836 (Uniprot-TrEMBL)
HDACProteinIPR000286 (InterPro) Family of proteins
IAMetaboliteCHEBI:132244 (ChEBI) AKA Indole acrylic acid
IDO1GeneProductENSG00000131203 (Ensembl)
IDO1ProteinP14902 (Uniprot-TrEMBL) AKA indoleamine 2,3-dioxygenase, in both immune and epithelial cells [PMID: 22688187]
IDO2GeneProduct169355 (Entrez Gene)
IDO2GeneProductENSG00000188676 (Ensembl)
IDO2ProteinQ6ZQW0 (Uniprot-TrEMBL) brain, liver and gut PW
IL4I1ProteinQ96RQ9 (Uniprot-TrEMBL)
ILAMetaboliteCHEBI:55528 (ChEBI) AKA Indole-3-lactic acid
INDO2GeneProduct3620 (Entrez Gene)
INMTGeneProduct11185 (Entrez Gene)
IPAMetaboliteCHEBI:43580 (ChEBI) AKA Indole-3-propionic acid
IndicanMetaboliteCHEBI:16700 (ChEBI)
Indole acetic glutamineMetaboliteCHEBI:176458 (ChEBI)
Indole-3-acetaldehydeMetabolite778 (Chemspider) AKA IAAId
Indole-3-acetamideMetaboliteCHEBI:16031 (ChEBI) AKA IAM
Indole-3-acetateMetabolite779 (Chemspider) AKA IAA, Indole Acetic Acid; Indole acetic acid is converted to skatole by Lactobacillus, Clostridium, Bacteroides, and others.
Indole-3-aldehydeMetaboliteCHEBI:28238 (ChEBI) AKA IAId
IndoleMetaboliteCHEBI:35581 (ChEBI)
IndolepyruvateMetaboliteC00331 (KEGG Compound) AKA IPYA, IP
Indolyl acryloyl glycineMetaboliteCHEBI:145761 (ChEBI)
KMOGeneProduct8564 (Entrez Gene) liver PW
KYAT1ProteinQ16773 (Uniprot-TrEMBL) KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1
KYAT2ProteinQ8N5Z0 (Uniprot-TrEMBL) KAT II/aminoadipate aminotransferase
KYAT3ProteinQ6YP21 (Uniprot-TrEMBL) KAT III/cysteine conjugate beta-lyase 2
KYAT4ProteinP00505 (Uniprot-TrEMBL) KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase
KYNUGeneProduct8942 (Entrez Gene)
Kynurenic AcidMetaboliteCHEBI:18344 (ChEBI)
L-KynurenineMetabolite343-65-7 (CAS) L-Kynurenine
L-TryptophanMetabolite73-22-3 (CAS)
MAOAGeneProduct4128 (Entrez Gene) AKA Monoamine Ozydase (MAO)
MelatoninMetaboliteHMDB0001389 (HMDB)
N-AcetylserotoninMetabolite1210-83-9 (CAS) AKA N-Acetylserotonin, NAS
N-MethylserotoninMetaboliteHMDB0004369 (HMDB)
N-MethyltryptamineMetaboliteCHEBI:28136 (ChEBI)
N-formylanthranilateMetaboliteQ27103061 (Wikidata) Formylanthranilate
Nicotinate and nicotinamide metabolismPathwayWP4210 (WikiPathways)
Phenylalanine, Tyrosine and Tryptophan metabolismPathwayWP3925 (WikiPathways)
Quinaldic AcidMetaboliteCHEBI:18386 (ChEBI)
QuinolinateMetabolite2777129 (Chemspider)
SCFAsMetaboliteCHEBI:26666 (ChEBI) Short-Chain-fatty-acids
STAT1GeneProductENSG00000115415 (Ensembl)
STAT1ProteinP42224 (Uniprot-TrEMBL) FN-gamma–dependent phosphorylation of STAT1
SerotoninMetabolite5013 (Chemspider) AKA 3-(2-Aminoethyl)-1H-indol-5-ol
TDO2GeneProduct6999 (Entrez Gene) liver PW
TMOProteinP48775 (Uniprot-TrEMBL) AKA Tryptophan 2,3-dioxygenase; abbreviation TMO is not know in UniProt (TDO2 is the gene name).
TNAProteinO07674 (Uniprot-TrEMBL) AKA Tryptophanase; Species: Haemophilus influenzae
TNAProteinP31014 (Uniprot-TrEMBL) AKA Tryptophanase (1); Species: Symbiobacterium thermophilum (strain T / IAM 14863)
TNAProteinP31015 (Uniprot-TrEMBL) AKA Tryptophanase (2); Species: Symbiobacterium thermophilum (strain T / IAM 14863)
TNAProteinQ9ZNA8 (Uniprot-TrEMBL) AKA Tryptophanase; Species: Proteus inconstans
TPH2GeneProduct121278 (Entrez Gene) produced in the brain; central synthesis
TpH1ProteinP17752 (Uniprot-TrEMBL) AKA Trp hydroxylase 1, produced in intestinal epithelial cells; peripheral synthesis
TrDProteinAKA Tryptophan Decarboxylase; protein from different species, is also expressed in plants (e.g. tobacco, PMID:10712558]
TryptamineMetabolite61-54-1 (CAS)
TryptopholMetaboliteCHEBI:17890 (ChEBI)
TyramineMetaboliteCHEBI:15760 (ChEBI)
Xanthurenic acidMetaboliteHMDB0000881 (HMDB)
acdAProteinJ7TF92 (Uniprot-TrEMBL) AKA acyl-CoA dehydrogenase; Species: Clostridium sporogenes (strain ATCC 15579)
acdAProteinP45867 (Uniprot-TrEMBL) AKA acyl-CoA dehydrogenase; Species: Bacillus subtilis (strain 168)
alpha-tocopherolMetaboliteCHEBI:22470 (ChEBI)
cholateMetaboliteCHEBI:29747 (ChEBI)
fldBProteinQ93AL9 (Uniprot-TrEMBL) AKA phenyllactate dehydratase; fldBC is know as two entries in UniProt (fldB and fldC); Species: Clostridium sporogenes
fldCProteinQ93AL8 (Uniprot-TrEMBL) AKA phenyllactate dehydratase; fldBC is know as two entries in UniProt (fldB and fldC); Species: Clostridium sporogenes
fldHProteinG9EZR6 (Uniprot-TrEMBL) AKA phenyllactate dehydrogenase or indolelactic acid dehydrogenase (ILDH); species: Clostridium sporogenes (strain ATCC 7955 / DSM 767 / NBRC 16411 / NCIMB 8053 / NCTC 8594 / PA 3679)
fldHProteinJ7SHB8 (Uniprot-TrEMBL) AKA phenyllactate dehydrogenase or indolelactic acid dehydrogenase (ILDH); species: Clostridium sporogenes (strain ATCC 15579)
indole-sulfonic acidMetabolite12904055 (PubChem-compound)
picolinateMetaboliteC10164 (KEGG Compound)
porBProteinQ9ZKA3 (Uniprot-TrEMBL) AKA pyruvate : ferrodoxin oxidoreductase B; Species: Helicobacter pylori (strain J99 / ATCC 700824) (Campylobacter pylori J99)
porCProteinAKA pyruvate : ferrodoxin oxidoreductase C; in UniProt known as porG; Species: Helicobacter pylori, various strains (32 in UniProt). "Helicobacter pylori (H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. " [PMID:30065554]
skatoleMetaboliteCHEBI:9171 (ChEBI) Indole acetic acid is converted to skatole by Lactobacillus, Clostridium, Bacteroides, and others.

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP465"
Personal tools