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].c2cac1c64f982-OxoadipateAnthranilatec64AKA IAA, Indole Acetic Acid; Indole acetic acid is converted to skatole by Lactobacillus, Clostridium, Bacteroides, and others.c64b245-Hydroxykynurenamine(S)-3-Hydroxybutanoyl-CoA5-Methoxyindoleacetate2-AminomuconateAKA 3-Hydroxy-L-kynurenine, 3H-KYNc64f98Formylanthranilate2-Aminomuconate4,8-DihydroxyquinolineCinnavalininate3-HydroxykynurenamineAKA IAAIdc642-Amino-3-carboxymuconatec64AKA 3-(2-Aminoethyl)-1H-indol-5-olf98AKA 3-Hydroxyanthranilate, 3-HAAc64f98Formyl-N-acetyl-5-methoxykynurenamine5-Hydroxyindoleacetatec64f98AKA indoleamine 2,3-dioxygenase, in both immune and epithelial cells [PMID: 22688187]c02predictedFormylkynurenineAKA Indole-3-lactic acidc64Indole acetic acid is converted to skatole by Lactobacillus, Clostridium, Bacteroides, and others.c64b24AKA IPYA, IPc64Unclear which specific protein acts in this reactionf98Acetyl-CoAAKA Trp hydroxylase 1, produced in intestinal epithelial cells; peripheral synthesisa06f98Family of proteinsef3Unclear which specific protein acts in this reaction.c64aka OADHAKA 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."f98Known under two EC numbers: aromatic-L-amino-acid/L-tryptophan decarboxylase [EC:4.1.1.28; EC:4.1.1.105]L-Kynureninec64f98AKA phenyllactate dehydrogenase or indolelactic acid dehydrogenase (ILDH); species: Clostridium sporogenes (strain ATCC 7955 / DSM 767 / NBRC 16411 / NCIMB 8053 / NCTC 8594 / PA 3679)AKA IAMAKA Aromatic amino acid aminotransferase, group of proteinsliver PWf98c64AKA kynureninaseShort-Chain-fatty-acidsc64KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1c59c64AKA 3-hydroxyanthraniate 3,4-dioxygenaseaka ABP1AKA 5-HIAAAKA Monoamine Ozydase (MAO)c64AKA Tryptophan 2,3-dioxygenase; abbreviation TMO is not know in UniProt (TDO2 is the gene name).liver PWf98produced in the brain; central synthesisf98AKA IAIdAKA N-Acetylserotonin, NASf98AKA Tryptophanase (2); Species: Symbiobacterium thermophilum (strain T / IAM 14863)brain, liver and gut PWf98c64AKA Indole acrylic acidc64AKA Indole-3-propionic acidc64AKA 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]deeAKA 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 sporogenesAKA phenyllactate dehydratase; fldBC is know as two entries in UniProt (fldB and fldC); Species: Clostridium sporogenesAKA acyl-CoA dehydrogenase; Species: Clostridium sporogenes (strain ATCC 15579)AKA Tryptophanase (1); Species: Symbiobacterium thermophilum (strain T / IAM 14863)AKA Tryptophanase; Species: Proteus inconstansAKA Tryptophanase; Species: Haemophilus influenzaec64KAT II/aminoadipate aminotransferasec59KAT III/cysteine conjugate beta-lyase 2c59KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferasec59c64AKA indoleamine 2,3-dioxygenase, in both immune and epithelial cells [PMID: 22688187]c02brain, liver and gut PWf98FN-gamma–dependent phosphorylation of STAT1Short-Chain-fatty-acidscentral synthesisf98peripheral synthesis (TPH1) vs central synthesis (TPH2)f98c64c64c64liver PWc64f98f98c64f98f98c64f98central synthesisf98f98c64c64c64(A) Decarboxylation of tryptophan to tryptamine by Clostridium sporogenes and Ruminococcus gnavus.c64c64c64c64c64c64c64c64c64b24c64f98b1ab1ab1ab1ab1a"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 pathwayPW:0000054Pathway Ontologytryptophan biosynthetic pathwayPW:0001280Pathway Ontologytryptophan degradation pathwayPW:0001281Pathway Ontologykynurenine metabolic pathwayPW:0001282Pathway Ontologyserotonin secreting cellCL:0000458Cell Ontologyaryl hydrocarbon receptor signaling pathwayPW:0000370Pathway Ontologyclassic metabolic pathwayPW:0000002Pathway Ontologysignaling pathwayPW:0000003Pathway Ontologyregulatory pathwayPW:0000004Pathway Ontologyenterochromaffin-like cellCL:0000504Cell Ontologytype EC enteroendocrine cellCL:0000577Cell Ontologyindoleamine and related compounds biosynthetic pathwayPW:0001238Pathway Ontologyindoleamine and related compounds metabolic pathwayPW:0000444Pathway Ontologyrno00380KEGG Pathwayhttps://www.genome.jp/dbget-bin/www_bget?pathway+rno0038029902437PubMedGut Microbiota Regulation of Tryptophan Metabolism in Health and DiseaseCell Host Microbe2018Allison AgusJulien PlanchaisHarry Sokol 231258331PubMedMicroorganisms, Tryptophan Metabolism, and Kynurenine Pathway: A Complex Interconnected Loop Influencing Human Health StatusInt J Tryptophan Res.2019Mona DehhaghiHamed Kazemi Shariat PanahiGilles J Guillemin31825083PubMedTryptophan Metabolism: A Link Between the Gut Microbiota and BrainAdv Nutr .2020Kan GaoChun-Long MuAitak FarziWei-Yun Zhu29468141PubMedImpact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan MetabolismFront Cell Infect Microbiol.2018Jing GaoKang XuHongnan LiuGang LiuMiaomiao BaiCan PengTiejun LiYulong Yin22688187PubMedThe microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent mannerMol Psychiatry2013G ClarkeS GrenhamP ScullyP FitzgeraldR D MoloneyF ShanahanT G DinanJ F Cryan25860609PubMedIndigenous bacteria from the gut microbiota regulate host serotonin biosynthesisCell2015Jessica M YanoKristie YuGregory P DonaldsonGauri G ShastriPhoebe AnnLiang MaCathryn R NaglerRustem F IsmagilovSarkis K MazmanianElaine Y Hsiao30619249PubMedButyrate Produced by Commensal Bacteria Down-Regulates Indolamine 2,3-Dioxygenase 1 ( IDO-1) Expression via a Dual Mechanism in Human Intestinal Epithelial CellsFront Immunol.2018Camille Martin-GallausiauxPierre LarraufieAnne JarryFabienne Béguet-CrespeLudovica MarinelliFlorence LedueFrank ReimannHervé M BlottièreNicolas Lapaque19826765PubMedStructure, expression, and function of kynurenine aminotransferases in human and rodent brainsCell Mol Life Sci.2010Qian HanTao CaiDanilo A. TagleJianyong Li30065554PubMedHelicobacter pylori in human health and disease: Mechanisms for local gastric and systemic effectsWorld J Gastroenterol.2018Denisse BravoAnilei HoareCristopher SotoManuel A ValenzuelaAndrew Fg Quest23797870PubMedSerotonin signalling in the gut--functions, dysfunctions and therapeutic targetsNat Rev Gastroenterol Hepatol.2013Gary M MaweJill M Hoffman