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/Assimilation → Amino Acids Degradation → Proteinogenic Amino Acids Degradation → L-tryptophan Degradation|
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.
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)
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
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 18.104.22.168) for the biosynthesis of pyridine nucleotides in anaerobically and aerobically grown Saccharomyces cerevisiae." Hoppe Seylers Z Physiol Chem 352(12);1654-8. PMID: 5145249
Alber06a: 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
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
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
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
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
Chen91a: 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
Christensen07a: 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
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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