Tryptophan metabolism (Homo sapiens)

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ArcPathVisio Brace Ellipse EndoplasmicReticulum GolgiApparatus HexagonPathVisio MimDegradation Mitochondria Octagon PentagonPathVisio Rectangle RoundedRectangle SarcoplasmicReticulum TriangleEquilateralEast TrianglePathVisio none Enterochromaffin Cell2-OxoadipateProtein found in differentspecies, leading to individualUniProt annotations.AnthranilateAhR ligandPMID:31258331.Indole-3-acetateUnclear which route is takento produce indolyl acryloyl glycine.5-hydroxykynurenamineendogenous serotonin in the gut is mainly released from ECs in response to a number of metabolites:(S)-3-Hydroxybutyryl-CoALEGEND5-MethoxyindoleacetateNAD+ and niacin production2-Aminomuconatemicrobial pathway interaction3-Hydroxy-L-kynurenineN-formylanthranilate2-Aminomuconate4,8-DihydroxyquinolineCinnavalininate3-HydroxykynurenamineIndole-3-acetaldehydeFormyl-5-hydroxykynurenamine2-Amino-3-carboxymuconateSerotonin3-HydroxyanthranilateFormyl-N-acetyl-5-methoxykynurenamine5-HydroxyindoleacetateQuinolinateALDH2IDO1IDO2GCDHALDH2Formylkynurenine4-(2-Amino-3-hydroxyphenyl)-2,4-dioxobutanoateILAskatoleIndolepyruvate4.1.1.-ASMTAcetyl-CoATpH1alpha-tocopherolIDO2HDAC1.5.1.-CYP1A1IndoleDLDMAOATrDMAOADDCCAT5-Hydroxy-L-tryptophanGlycolysis/GluconeogenesisSTAT1Nicotinate and nicotinamide metabolismDDCAHRDDCMAOAButyrateACAT1INDO2L-KynurenineAFMIDMelatoninAANATALDH8A1Benzoate degradation via hydroxylationAOX1IL4I15-HydroxykynurenineAADATACMSDXanthurenic acidfldHIndole-3-acetamideN-MethylserotoninArATKMOTryptopholTryptamineKYNU5-Hydroxy-N-formylkynurenine4,6-Dihydroxyquinolineindole-sulfonic acidSCFAsINMTL-TryptophanKynurenic AcidAcetoacetyl-CoAIndicanN-MethyltryptaminePhenylalanine, Tyrosine and Tryptophan metabolismCrotonoyl-CoAHAAOAOC15-HydroxyindoleacetaldehydeMAOAIDO1KYNU4-aminobenzoic acidINMTIndolyl acryloyl glycineTMOECHS1TDO2TPH2Tyramine6-HydroxymelatoninIndole-3-aldehydeGlutaryl-CoAcholateN-AcetylserotoninTNAASMTKYAT1KYAT2KYAT3KYAT4IDO2AFMIDKYNUpicolinateHADHIDO2Potential AhR ligand(but in supraphysiological concentrations)IAIPAporCporBacdAfldHfldBfldCacdATNATNATNAQuinaldic AcidIndole acetic glutamineAhR ligandPMID:31825083.AHRAHRAHRIDO1IDO2STAT1PSTAT1SCFAsName: Tryptophan metabolismOrganism: Homo sapiens


Description

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

Originally adapted from: [KEGG](https://www.genome.jp/kegg-bin/show_pathway?hsa00380), and expanded with information from [Agus 2018](https://doi.org/10.1016/j.chom.2018.05.003), [Dehhaghi 2019](https://doi.org/10.1177/1178646919852996), and [Gao 2020](https://doi.org/10.1093/advances/nmz127).

"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](https://doi.org/10.1016/j.chom.2018.05.003).

Proteins on this pathway have targeted assays available via the [CPTAC Assay Portal](https://assays.cancer.gov/available_assays?wp_id=WP465).

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Quality Tags

Image:Featured.pngFeatured version
Image:Curated.pngApproved version
Image:Unconnected.pngFix interactions
Image:MissingXref.pngAnnotate nodes

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
137474
Featured
Approved
view15:02, 2 March 2025EgonwModified description
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).

External references

DataNodes

View all...
Name  ↓Type  ↓Database reference  ↓Comment  ↓
(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"