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MetaCyc Pathway: L-tryptophan degradation III (eukaryotic)
Inferred from experiment

Enzyme View:

Pathway diagram: L-tryptophan degradation III (eukaryotic)

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: the kynurenine pathway

Superclasses: Degradation/Utilization/AssimilationAmino Acids DegradationProteinogenic Amino Acids DegradationL-tryptophan Degradation

Some taxa known to possess this pathway include : Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae

Expected Taxonomic Range: Fungi, Metazoa

Aerobic L-tryptophan degradation, also known as the L-kynurenine pathway, is the major route of L-tryptophan degradation in mammals. This complex network of biochemical transformations generates a number of neurologically active compounds, including quinolinate and kynurenate, some of which associated with neurological disorders (or a recent review see [Stone02]). The enzymology of the kynurenine pathway in humans and in yeast has been largely elucidated over the last 20 years, and the genes for most of the enzymes have been identified [AlberatiGiani96, AlberatiGiani97, Calderone02, Comings95, Kucharczyk98, Iwamoto95, Schott71].

This pathway spans the cytoplasmic and mitochondrial compartments. The first 8 reactions occur in the cytoplasm, but 2-oxoadipate is transported into the mitochondrial matrix where the rest of the reactions occur.

Subpathways: 2-amino-3-carboxymuconate semialdehyde degradation to glutaryl-CoA, L-tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde, glutaryl-CoA degradation

Variants: L-tryptophan degradation I (via anthranilate), L-tryptophan degradation II (via pyruvate), L-tryptophan degradation IV (via indole-3-lactate), L-tryptophan degradation V (side chain pathway), L-tryptophan degradation VI (via tryptamine), L-tryptophan degradation VII (via indole-3-pyruvate), L-tryptophan degradation VIII (to tryptophol), L-tryptophan degradation IX, L-tryptophan degradation X (mammalian, via tryptamine), L-tryptophan degradation XI (mammalian, via kynurenine), L-tryptophan degradation XII (Geobacillus)

Created 07-Sep-2007 by Caspi R, SRI International


AlberatiGiani96: Alberati-Giani D, Buchli R, Malherbe P, Broger C, Lang G, Kohler C, Lahm HW, Cesura AM (1996). "Isolation and expression of a cDNA clone encoding human kynureninase." Eur J Biochem 239(2);460-8. PMID: 8706755

AlberatiGiani97: Alberati-Giani D, Cesura AM, Broger C, Warren WD, Rover S, Malherbe P (1997). "Cloning and functional expression of human kynurenine 3-monooxygenase." FEBS Lett 410(2-3);407-12. PMID: 9237672

Calderone02: Calderone V, Trabucco M, Menin V, Negro A, Zanotti G (2002). "Cloning of human 3-hydroxyanthranilic acid dioxygenase in Escherichia coli: characterisation of the purified enzyme and its in vitro inhibition by Zn2+." Biochim Biophys Acta 1596(2);283-92. PMID: 12007609

Comings95: Comings DE, Muhleman D, Dietz G, Sherman M, Forest GL (1995). "Sequence of human tryptophan 2,3-dioxygenase (TDO2): presence of a glucocorticoid response-like element composed of a GTT repeat and an intronic CCCCT repeat." Genomics 29(2);390-6. PMID: 8666386

Iwamoto95: Iwamoto Y, Lee IS, Tsubaki M, Kido R (1995). "Tryptophan 2,3-dioxygenase in Saccharomyces cerevisiae." Can J Microbiol 41(1);19-26. PMID: 7728653

Kucharczyk98: Kucharczyk R, Zagulski M, Rytka J, Herbert CJ (1998). "The yeast gene YJR025c encodes a 3-hydroxyanthranilic acid dioxygenase and is involved in nicotinic acid biosynthesis." FEBS Lett 424(3);127-30. PMID: 9539135

Schott71: Schott HH, Staudinger H, Ullrich V (1971). "The regulatory function of L-kynurenine 3-hydroxylase (EC for the biosynthesis of pyridine nucleotides in anaerobically and aerobically grown Saccharomyces cerevisiae." Hoppe Seylers Z Physiol Chem 352(12);1654-8. PMID: 5145249

Stone02: Stone TW, Darlington LG (2002). "Endogenous kynurenines as targets for drug discovery and development." Nat Rev Drug Discov 1(8);609-20. PMID: 12402501

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Alber06: Alber BE, Spanheimer R, Ebenau-Jehle C, Fuchs G (2006). "Study of an alternate glyoxylate cycle for acetate assimilation by Rhodobacter sphaeroides." Mol Microbiol 61(2);297-309. PMID: 16856937

Austin09: Austin CJ, Astelbauer F, Kosim-Satyaputra P, Ball HJ, Willows RD, Jamie JF, Hunt NH (2009). "Mouse and human indoleamine 2,3-dioxygenase display some distinct biochemical and structural properties." Amino Acids 36(1);99-106. PMID: 18274832

Bairoch93a: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Ball09: Ball HJ, Yuasa HJ, Austin CJ, Weiser S, Hunt NH (2009). "Indoleamine 2,3-dioxygenase-2; a new enzyme in the kynurenine pathway." Int J Biochem Cell Biol 41(3);467-71. PMID: 18282734

Barker82: Barker HA, Kahn JM, Hedrick L (1982). "Pathway of lysine degradation in Fusobacterium nucleatum." J Bacteriol 152(1);201-7. PMID: 6811551

Basran08: Basran J, Rafice SA, Chauhan N, Efimov I, Cheesman MR, Ghamsari L, Raven EL (2008). "A kinetic, spectroscopic, and redox study of human tryptophan 2,3-dioxygenase." Biochemistry 47(16);4752-60. PMID: 18370401

Batabyal07: Batabyal D, Yeh SR (2007). "Human tryptophan dioxygenase: a comparison to indoleamine 2,3-dioxygenase." J Am Chem Soc 129(50);15690-701. PMID: 18027945

Bendrat93: Bendrat K, Buckel W (1993). "Cloning, sequencing and expression of the gene encoding the carboxytransferase subunit of the biotin-dependent Na+ pump glutaconyl-CoA decarboxylase from Acidaminococcus fermentans in Escherichia coli." Eur J Biochem 1993;211(3);697-702. PMID: 8382157

Bennett84: Bennett MJ, Hosking GP, Smith MF, Gray RG, Middleton B (1984). "Biochemical investigations on a patient with a defect in cytosolic acetoacetyl-CoA thiolase, associated with mental retardation." J Inherit Metab Dis 7(3);125-8. PMID: 6150136

Berg07: Berg IA, Kockelkorn D, Buckel W, Fuchs G (2007). "A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea." Science 318(5857);1782-6. PMID: 18079405

Brady75: Brady FO (1975). "Tryptophan 2,3-dioxygenase: a review of the roles of the heme and copper cofactors in catalysis." Bioinorg Chem 5(2);167-82. PMID: 178384

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Breton00: Breton J, Avanzi N, Magagnin S, Covini N, Magistrelli G, Cozzi L, Isacchi A (2000). "Functional characterization and mechanism of action of recombinant human kynurenine 3-hydroxylase." Eur J Biochem 267(4);1092-9. PMID: 10672018

Brown86: Brown D, Hitchcock MJ, Katz E (1986). "Purification and characterization of kynurenine formamidase activities from Streptomyces parvulus." Can J Microbiol 32(6);465-72. PMID: 2425918

Buckel83: Buckel W, Semmler R (1983). "Purification, characterisation and reconstitution of glutaconyl-CoA decarboxylase, a biotin-dependent sodium pump from anaerobic bacteria." Eur J Biochem 1983;136(2);427-34. PMID: 6628393

Chen91c: Chen GL, Balfe A, Erwa W, Hoefler G, Gaertner J, Aikawa J, Chen WW (1991). "Import of human bifunctional enzyme into peroxisomes of human hepatoma cells in vitro." Biochem Biophys Res Commun 178(3);1084-91. PMID: 1651711

Chen94: Chen D, Swenson RP (1994). "Cloning, sequence analysis, and expression of the genes encoding the two subunits of the methylotrophic bacterium W3A1 electron transfer flavoprotein." J Biol Chem 269(51);32120-30. PMID: 7798207

Christensen07: Christensen M, Duno M, Lund AM, Skovby F, Christensen E (2007). "Xanthurenic aciduria due to a mutation in KYNU encoding kynureninase." J Inherit Metab Dis 30(2);248-55. PMID: 17334708

Colabroy05: Colabroy KL, Begley TP (2005). "Tryptophan catabolism: identification and characterization of a new degradative pathway." J Bacteriol 187(22);7866-9. PMID: 16267312

Colby92: Colby GD, Chen JS (1992). "Purification and properties of 3-hydroxybutyryl-coenzyme A dehydrogenase from Clostridium beijerinckii ("Clostridium butylicum") NRRL B593." Appl Environ Microbiol 58(10);3297-302. PMID: 1444364

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Mon Feb 8, 2016, biocyc13.