This pathway describes the metabolism of tryptophan, an essential amino acid. Originally adapted from: [https://www.genome.jp/kegg-bin/show_pathway?hsa00380 KEGG], and expanded with information from [https://doi.org/10.1016/j.chom.2018.05.003 Agus 2018], [https://doi.org/10.1177%2F1178646919852996 Dehhaghi 2019], and [https://doi.org/10.1093/advances/nmz127 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)." [https://doi.org/10.1016/j.chom.2018.05.003 Agus 2018]. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP465 CPTAC Assay Portal]. c2c ac1 c64 f98 2-Oxoadipate Anthranilate c64 AKA IAA, Indole Acetic Acid; Indole acetic acid is converted to skatole by Lactobacillus, Clostridium, Bacteroides, and others. c64 b24 5-Hydroxykynurenamine (S)-3-Hydroxybutanoyl-CoA 5-Methoxyindoleacetate 2-Aminomuconate AKA 3-Hydroxy-L-kynurenine, 3H-KYN c64 f98 Formylanthranilate 2-Aminomuconate 4,8-Dihydroxyquinoline Cinnavalininate 3-Hydroxykynurenamine AKA IAAId c64 2-Amino-3-carboxymuconate c64 AKA 3-(2-Aminoethyl)-1H-indol-5-ol f98 AKA 3-Hydroxyanthranilate, 3-HAA c64 f98 Formyl-N-acetyl-5-methoxykynurenamine 5-Hydroxyindoleacetate c64 f98 AKA indoleamine 2,3-dioxygenase, in both immune and epithelial cells [PMID: 22688187] c02 predicted Formylkynurenine AKA Indole-3-lactic acid c64 Indole acetic acid is converted to skatole by Lactobacillus, Clostridium, Bacteroides, and others. c64 b24 AKA IPYA, IP c64 Unclear which specific protein acts in this reaction f98 Acetyl-CoA AKA Trp hydroxylase 1, produced in intestinal epithelial cells; peripheral synthesis a06 f98 Family of proteins ef3 Unclear which specific protein acts in this reaction. c64 aka OADH AKA Tryptophan Decarboxylase; protein from different species, is also expressed in plants (e.g. tobacco, PMID:10712558] In Agus et al, this protein is called "AAAD", aka "aromatic amino acid decarboxylase", which is known in UniProt at DCC; AAAD is an unrelated protein and its addition to Figure 2 of this paper is questionable [PMID:29902437]. Fig. 1 [PMID:31825083] mentions AADC, in peripheral synthesis. f98 "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." f98 Known under two EC numbers: aromatic-L-amino-acid/L-tryptophan decarboxylase [EC:4.1.1.28; EC:4.1.1.105] L-Kynurenine c64 f98 AKA phenyllactate dehydrogenase or indolelactic acid dehydrogenase (ILDH); species: Clostridium sporogenes (strain ATCC 7955 / DSM 767 / NBRC 16411 / NCIMB 8053 / NCTC 8594 / PA 3679) AKA IAM AKA Aromatic amino acid aminotransferase, group of proteins liver PW f98 c64 AKA kynureninase Short-Chain-fatty-acids c64 KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1 c59 c64 AKA 3-hydroxyanthraniate 3,4-dioxygenase aka ABP1 AKA 5-HIAA AKA Monoamine Ozydase (MAO) c64 AKA Tryptophan 2,3-dioxygenase; abbreviation TMO is not know in UniProt (TDO2 is the gene name). liver PW f98 produced in the brain; central synthesis f98 AKA IAId AKA N-Acetylserotonin, NAS f98 AKA Tryptophanase (2); Species: Symbiobacterium thermophilum (strain T / IAM 14863) brain, liver and gut PW f98 c64 AKA Indole acrylic acid c64 AKA Indole-3-propionic acid c64 AKA 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] dee AKA pyruvate : ferrodoxin oxidoreductase B; Species: Helicobacter pylori (strain J99 / ATCC 700824) (Campylobacter pylori J99) AKA acyl-CoA dehydrogenase; Species: Bacillus subtilis (strain 168) AKA phenyllactate dehydrogenase or indolelactic acid dehydrogenase (ILDH); species: Clostridium sporogenes (strain ATCC 15579) AKA phenyllactate dehydratase; fldBC is know as two entries in UniProt (fldB and fldC); Species: Clostridium sporogenes AKA phenyllactate dehydratase; fldBC is know as two entries in UniProt (fldB and fldC); Species: Clostridium sporogenes AKA acyl-CoA dehydrogenase; Species: Clostridium sporogenes (strain ATCC 15579) AKA Tryptophanase (1); Species: Symbiobacterium thermophilum (strain T / IAM 14863) AKA Tryptophanase; Species: Proteus inconstans AKA Tryptophanase; Species: Haemophilus influenzae c64 KAT II/aminoadipate aminotransferase c59 KAT III/cysteine conjugate beta-lyase 2 c59 KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase c59 c64 AKA indoleamine 2,3-dioxygenase, in both immune and epithelial cells [PMID: 22688187] c02 brain, liver and gut PW f98 FN-gamma–dependent phosphorylation of STAT1 Short-Chain-fatty-acids central synthesis f98 peripheral synthesis (TPH1) vs central synthesis (TPH2) f98 c64 c64 c64 liver PW c64 f98 f98 c64 f98 f98 c64 f98 central synthesis f98 f98 c64 c64 c64 (A) Decarboxylation of tryptophan to tryptamine by Clostridium sporogenes and Ruminococcus gnavus. c64 c64 c64 c64 c64 c64 c64 c64 c64 b24 c64 f98 b1a b1a b1a b1a b1a "Enterochromaffin cells (EC) containing 5-hydroxytryptamine (5-HT) are present throughout the ductal system of the pancreas, including the small ducts that are the major site of HCO3− secretion." Source:[https://www.sciencedirect.com/science/article/pii/B9780123820266000518] tryptophan metabolic pathway PW:0000054 Pathway Ontology tryptophan biosynthetic pathway PW:0001280 Pathway Ontology tryptophan degradation pathway PW:0001281 Pathway Ontology kynurenine metabolic pathway PW:0001282 Pathway Ontology serotonin secreting cell CL:0000458 Cell Ontology aryl hydrocarbon receptor signaling pathway PW:0000370 Pathway Ontology classic metabolic pathway PW:0000002 Pathway Ontology signaling pathway PW:0000003 Pathway Ontology regulatory pathway PW:0000004 Pathway Ontology enterochromaffin-like cell CL:0000504 Cell Ontology type EC enteroendocrine cell CL:0000577 Cell Ontology indoleamine and related compounds biosynthetic pathway PW:0001238 Pathway Ontology indoleamine and related compounds metabolic pathway PW:0000444 Pathway Ontology rno00380 KEGG Pathway https://www.genome.jp/dbget-bin/www_bget?pathway+rno00380 29902437 PubMed Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease Cell Host Microbe 2018 Allison Agus Julien Planchais Harry Sokol 2 31258331 PubMed Microorganisms, Tryptophan Metabolism, and Kynurenine Pathway: A Complex Interconnected Loop Influencing Human Health Status Int J Tryptophan Res. 2019 Mona Dehhaghi Hamed Kazemi Shariat Panahi Gilles J Guillemin 31825083 PubMed Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain Adv Nutr . 2020 Kan Gao Chun-Long Mu Aitak Farzi Wei-Yun Zhu 29468141 PubMed Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism Front Cell Infect Microbiol. 2018 Jing Gao Kang Xu Hongnan Liu Gang Liu Miaomiao Bai Can Peng Tiejun Li Yulong Yin 22688187 PubMed The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner Mol Psychiatry 2013 G Clarke S Grenham P Scully P Fitzgerald R D Moloney F Shanahan T G Dinan J F Cryan 25860609 PubMed Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis Cell 2015 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 30619249 PubMed 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 Camille Martin-Gallausiaux Pierre Larraufie Anne Jarry Fabienne Béguet-Crespe Ludovica Marinelli Florence Ledue Frank Reimann Hervé M Blottière Nicolas Lapaque 19826765 PubMed Structure, expression, and function of kynurenine aminotransferases in human and rodent brains Cell Mol Life Sci. 2010 Qian Han Tao Cai Danilo A. Tagle Jianyong Li 30065554 PubMed Helicobacter pylori in human health and disease: Mechanisms for local gastric and systemic effects World J Gastroenterol. 2018 Denisse Bravo Anilei Hoare Cristopher Soto Manuel A Valenzuela Andrew Fg Quest 23797870 PubMed Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets Nat Rev Gastroenterol Hepatol. 2013 Gary M Mawe Jill M Hoffman