Tryptophan metabolism (Homo sapiens)
From WikiPathways
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.
Quality Tags
Ontology Terms
Bibliography
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- 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
- 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
- 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
- ''''; https://www.genome.jp/dbget-bin/www_bget?pathway+rno00380,
- 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
- 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
- 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
- Jing Gao, Kang Xu, Hongnan Liu, Gang Liu, Miaomiao Bai, Can Peng, Tiejun Li, Yulong Yin; ''''; , PubMed Europe PMC Scholia
- 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
- 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
- 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
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
(S)-3-Hydroxy butyryl-CoA | Metabolite | C01144 (KEGG Compound) | (S)-3-Hydroxybutanoyl-CoA |
1.5.1.- | GeneProduct | 1.5.1.- (Enzyme Nomenclature) | Unclear which specific protein acts in this reaction. |
2-Amino-3-carboxymuconate | Metabolite | C04409 (KEGG Compound) | 2-Amino-3-carboxymuconate |
2-Aminomuconate | Metabolite | C02220 (KEGG Compound) | 2-Aminomuconate |
2-Aminomuconate | Metabolite | C03824 (KEGG Compound) | 2-Aminomuconate |
2-Oxoadipate | Metabolite | 19951093 (Chemspider) | 2-Oxoadipate |
3-Hydroxy- L-kynurenine | Metabolite | C03227 (KEGG Compound) | AKA 3-Hydroxy-L-kynurenine, 3H-KYN |
3-Hydroxyanthranilate | Metabolite | 7822291 (Chemspider) | AKA 3-Hydroxyanthranilate, 3-HAA |
3-Hydroxykynurenamine | Metabolite | HMDB0060281 (HMDB) | 3-Hydroxykynurenamine |
4,6-Dihydroxyquinoline | Metabolite | HMDB0004077 (HMDB) | |
4,8-Dihydroxyquinoline | Metabolite | CHEBI:28883 (ChEBI) | 4,8-Dihydroxyquinoline |
4-(2-Amino-3-hydroxyphenyl)- 2,4-dioxobutanoate | Metabolite | HMDB0004083 (HMDB) | |
4-aminobenzoic acid | Metabolite | CHEBI:30753 (ChEBI) | |
4.1.1.- | GeneProduct | 4.1.1.- (Enzyme Nomenclature) | Unclear which specific protein acts in this reaction |
5-Hydroxy-L-tryptophan | Metabolite | HMDB0000472 (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-formylkynurenine | Metabolite | HMDB0004086 (HMDB) | |
5-Hydroxyindoleacetaldehyde | Metabolite | HMDB0004073 (HMDB) | AKA 5-HIAA |
5-Hydroxyindoleacetate | Metabolite | 10637170 (Chemspider) | 5-Hydroxyindoleacetate |
5-Hydroxykynurenine | Metabolite | 484-78-6 (CAS) | |
5-Methoxyindoleacetate | Metabolite | 14533147 (Chemspider) | 5-Methoxyindoleacetate |
5-hydroxykynurenamine | Metabolite | CHEBI:62214 (ChEBI) | 5-Hydroxykynurenamine |
6-Hydroxymelatonin | Metabolite | 2208-41-5 (CAS) | |
AADAT | GeneProduct | 56267 (Entrez Gene) | |
AANAT | GeneProduct | 15 (Entrez Gene) | |
ACAT1 | GeneProduct | 38 (Entrez Gene) | |
ACMSD | GeneProduct | 130013 (Entrez Gene) | |
AFMID | GeneProduct | 125061 (Entrez Gene) | |
AHR | Protein | AHR (HGNC) | |
ALDH2 | GeneProduct | 217 (Entrez Gene) | |
ALDH2 | Protein | P05091 (Uniprot-TrEMBL) | |
ALDH8A1 | GeneProduct | 64577 (Entrez Gene) | |
AOC1 | GeneProduct | 26 (Entrez Gene) | aka ABP1 |
AOX1 | GeneProduct | 316 (Entrez Gene) | |
ASMT | GeneProduct | 438 (Entrez Gene) | |
Acetoacetyl-CoA | Metabolite | C00332 (KEGG Compound) | |
Acetyl-CoA | Metabolite | 72-89-9 (CAS) | Acetyl-CoA |
Anthranilate | Metabolite | 4573598 (Chemspider) | Anthranilate |
ArAT | Protein | 2.6.1.57 (Enzyme Nomenclature) | AKA Aromatic amino acid aminotransferase, group of proteins |
Benzoate degradation via hydroxylation | Pathway | ||
Butyrate | Metabolite | CHEBI:17968 (ChEBI) | |
CAT | GeneProduct | 847 (Entrez Gene) | |
CYP1A1 | GeneProduct | 1543 (Entrez Gene) | |
Cinnavalininate | Metabolite | C05640 (KEGG Compound) | Cinnavalininate |
Crotonoyl-CoA | Metabolite | C00877 (KEGG Compound) | |
DDC | GeneProduct | 1644 (Entrez Gene) | Known under two EC numbers: aromatic-L-amino-acid/L-tryptophan decarboxylase [EC:4.1.1.28; EC:4.1.1.105] |
DLD | GeneProduct | 1738 (Entrez Gene) | aka OADH |
ECHS1 | GeneProduct | 1892 (Entrez Gene) | |
Formyl-5-hydroxy kynurenamine | Metabolite | HMDB0012948 (HMDB) | |
Formyl-N-acetyl-5- methoxykynurenamine | Metabolite | C05642 (KEGG Compound) | Formyl-N-acetyl-5-methoxykynurenamine |
Formylkynurenine | Metabolite | 1022-31-7 (CAS) | Formylkynurenine |
GCDH | GeneProduct | 2639 (Entrez Gene) | predicted |
Glutaryl-CoA | Metabolite | C00527 (KEGG Compound) | |
Glycolysis/Gluconeogenesis | Pathway | WP534 (WikiPathways) | |
HAAO | GeneProduct | 23498 (Entrez Gene) | AKA 3-hydroxyanthraniate 3,4-dioxygenase |
HADH | Protein | Q16836 (Uniprot-TrEMBL) | |
HDAC | Protein | IPR000286 (InterPro) | Family of proteins |
IA | Metabolite | CHEBI:132244 (ChEBI) | AKA Indole acrylic acid |
IDO1 | GeneProduct | ENSG00000131203 (Ensembl) | |
IDO1 | Protein | P14902 (Uniprot-TrEMBL) | AKA indoleamine 2,3-dioxygenase, in both immune and epithelial cells [PMID: 22688187] |
IDO2 | GeneProduct | 169355 (Entrez Gene) | |
IDO2 | GeneProduct | ENSG00000188676 (Ensembl) | |
IDO2 | Protein | Q6ZQW0 (Uniprot-TrEMBL) | brain, liver and gut PW |
IL4I1 | Protein | Q96RQ9 (Uniprot-TrEMBL) | |
ILA | Metabolite | CHEBI:55528 (ChEBI) | AKA Indole-3-lactic acid |
INDO2 | GeneProduct | 3620 (Entrez Gene) | |
INMT | GeneProduct | 11185 (Entrez Gene) | |
IPA | Metabolite | CHEBI:43580 (ChEBI) | AKA Indole-3-propionic acid |
Indican | Metabolite | CHEBI:16700 (ChEBI) | |
Indole acetic glutamine | Metabolite | CHEBI:176458 (ChEBI) | |
Indole-3-acetaldehyde | Metabolite | 778 (Chemspider) | AKA IAAId |
Indole-3-acetamide | Metabolite | CHEBI:16031 (ChEBI) | AKA IAM |
Indole-3-acetate | Metabolite | 779 (Chemspider) | AKA IAA, Indole Acetic Acid; Indole acetic acid is converted to skatole by Lactobacillus, Clostridium, Bacteroides, and others. |
Indole-3-aldehyde | Metabolite | CHEBI:28238 (ChEBI) | AKA IAId |
Indole | Metabolite | CHEBI:35581 (ChEBI) | |
Indolepyruvate | Metabolite | C00331 (KEGG Compound) | AKA IPYA, IP |
Indolyl acryloyl glycine | Metabolite | CHEBI:145761 (ChEBI) | |
KMO | GeneProduct | 8564 (Entrez Gene) | liver PW |
KYAT1 | Protein | Q16773 (Uniprot-TrEMBL) | KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1 |
KYAT2 | Protein | Q8N5Z0 (Uniprot-TrEMBL) | KAT II/aminoadipate aminotransferase |
KYAT3 | Protein | Q6YP21 (Uniprot-TrEMBL) | KAT III/cysteine conjugate beta-lyase 2 |
KYAT4 | Protein | P00505 (Uniprot-TrEMBL) | KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase |
KYNU | GeneProduct | 8942 (Entrez Gene) | |
Kynurenic Acid | Metabolite | CHEBI:18344 (ChEBI) | |
L-Kynurenine | Metabolite | 343-65-7 (CAS) | L-Kynurenine |
L-Tryptophan | Metabolite | 73-22-3 (CAS) | |
MAOA | GeneProduct | 4128 (Entrez Gene) | AKA Monoamine Ozydase (MAO) |
Melatonin | Metabolite | HMDB0001389 (HMDB) | |
N-Acetylserotonin | Metabolite | 1210-83-9 (CAS) | AKA N-Acetylserotonin, NAS |
N-Methylserotonin | Metabolite | HMDB0004369 (HMDB) | |
N-Methyltryptamine | Metabolite | CHEBI:28136 (ChEBI) | |
N-formylanthranilate | Metabolite | Q27103061 (Wikidata) | Formylanthranilate |
Nicotinate and nicotinamide metabolism | Pathway | WP4210 (WikiPathways) | |
Phenylalanine, Tyrosine and Tryptophan metabolism | Pathway | WP3925 (WikiPathways) | |
Quinaldic Acid | Metabolite | CHEBI:18386 (ChEBI) | |
Quinolinate | Metabolite | 2777129 (Chemspider) | |
SCFAs | Metabolite | CHEBI:26666 (ChEBI) | Short-Chain-fatty-acids |
STAT1 | GeneProduct | ENSG00000115415 (Ensembl) | |
STAT1 | Protein | P42224 (Uniprot-TrEMBL) | FN-gamma–dependent phosphorylation of STAT1 |
Serotonin | Metabolite | 5013 (Chemspider) | AKA 3-(2-Aminoethyl)-1H-indol-5-ol |
TDO2 | GeneProduct | 6999 (Entrez Gene) | liver PW |
TMO | Protein | P48775 (Uniprot-TrEMBL) | AKA Tryptophan 2,3-dioxygenase; abbreviation TMO is not know in UniProt (TDO2 is the gene name). |
TNA | Protein | O07674 (Uniprot-TrEMBL) | AKA Tryptophanase; Species: Haemophilus influenzae |
TNA | Protein | P31014 (Uniprot-TrEMBL) | AKA Tryptophanase (1); Species: Symbiobacterium thermophilum (strain T / IAM 14863) |
TNA | Protein | P31015 (Uniprot-TrEMBL) | AKA Tryptophanase (2); Species: Symbiobacterium thermophilum (strain T / IAM 14863) |
TNA | Protein | Q9ZNA8 (Uniprot-TrEMBL) | AKA Tryptophanase; Species: Proteus inconstans |
TPH2 | GeneProduct | 121278 (Entrez Gene) | produced in the brain; central synthesis |
TpH1 | Protein | P17752 (Uniprot-TrEMBL) | AKA Trp hydroxylase 1, produced in intestinal epithelial cells; peripheral synthesis |
TrD | Protein | AKA Tryptophan Decarboxylase; protein from different species, is also expressed in plants (e.g. tobacco, PMID:10712558] | |
Tryptamine | Metabolite | 61-54-1 (CAS) | |
Tryptophol | Metabolite | CHEBI:17890 (ChEBI) | |
Tyramine | Metabolite | CHEBI:15760 (ChEBI) | |
Xanthurenic acid | Metabolite | HMDB0000881 (HMDB) | |
acdA | Protein | J7TF92 (Uniprot-TrEMBL) | AKA acyl-CoA dehydrogenase; Species: Clostridium sporogenes (strain ATCC 15579) |
acdA | Protein | P45867 (Uniprot-TrEMBL) | AKA acyl-CoA dehydrogenase; Species: Bacillus subtilis (strain 168) |
alpha-tocopherol | Metabolite | CHEBI:22470 (ChEBI) | |
cholate | Metabolite | CHEBI:29747 (ChEBI) | |
fldB | Protein | Q93AL9 (Uniprot-TrEMBL) | AKA phenyllactate dehydratase; fldBC is know as two entries in UniProt (fldB and fldC); Species: Clostridium sporogenes |
fldC | Protein | Q93AL8 (Uniprot-TrEMBL) | AKA phenyllactate dehydratase; fldBC is know as two entries in UniProt (fldB and fldC); Species: Clostridium sporogenes |
fldH | Protein | G9EZR6 (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) |
fldH | Protein | J7SHB8 (Uniprot-TrEMBL) | AKA phenyllactate dehydrogenase or indolelactic acid dehydrogenase (ILDH); species: Clostridium sporogenes (strain ATCC 15579) |
indole-sulfonic acid | Metabolite | 12904055 (PubChem-compound) | |
picolinate | Metabolite | C10164 (KEGG Compound) | |
porB | Protein | Q9ZKA3 (Uniprot-TrEMBL) | AKA pyruvate : ferrodoxin oxidoreductase B; Species: Helicobacter pylori (strain J99 / ATCC 700824) (Campylobacter pylori J99) |
porC | Protein | 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] | |
skatole | Metabolite | CHEBI:9171 (ChEBI) | Indole acetic acid is converted to skatole by Lactobacillus, Clostridium, Bacteroides, and others. |
Annotated Interactions
No annotated interactions