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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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for maintenance.
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MetaCyc Enzyme: tryptophan 2,3-dioxygenase

Gene: TDO2 Accession Number: G-11448 (MetaCyc)

Synonyms: TDO

Species: Homo sapiens

Summary:
A 2009 review described the subunit structure of eukaryotic tryptophan 2,3-dioxygenase as a tetramer [Rafice09]. Although the rat enzyme was reported to be a tetramer [Schutz72], the subunit structure of the human enzyme remains to be experimentally characterized. It is shown here as a monomer, to be updated when experimental data are available.

Despite this lack of subunit structure characterization, the reaction mechanism of the recombinant human enzyme expressed in Escherichia coli has been studied in detail using kinetic, spectroscopic and redox analyses [Basran08, Batabyal07].

In mammals this enzyme is present mostly in liver and is also found in skin. It is regulated by glucocorticoid hormones and its physiological substrate L-tryptophan. In other tissues, indoleamine 2,3-dioxygenase catalyzes the conversion of L-tryptophan to N-formylkynurenine (in [Batabyal07]). Catalytic differences between these two enzymes have been shown [Basran08]. Reviewed in [Rafice09].

Gene Citations: [Comings95]

Map Position: [156,824,847 -> 156,841,550]

Molecular Weight of Polypeptide: 47.872 kD (from nucleotide sequence)

Unification Links: ArrayExpress:P48775 , Entrez-gene:6999 , Mint:MINT-1446261 , PhosphoSite:P48775 , Pride:P48775 , Protein Model Portal:P48775 , SMR:P48775 , String:9606.ENSP00000281525 , UniProt:P48775

Relationship Links: InterPro:IN-FAMILY:IPR004981 , Panther:IN-FAMILY:PTHR10138 , Pfam:IN-FAMILY:PF03301

Gene-Reaction Schematic: ?


Enzymatic reaction of: tryptophan 2,3-dioxygenase

EC Number: 1.13.11.11

L-tryptophan + oxygen <=> N-formylkynurenine

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

Alternative Substrates for L-tryptophan: D-tryptophan [Batabyal07 ]

In Pathways: tryptophan degradation III (eukaryotic) , tryptophan degradation XI (mammalian, via kynurenine) , NAD biosynthesis II (from tryptophan) , tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde

Cofactors or Prosthetic Groups: heme b [Rafice09]

Kinetic Parameters:

Substrate
Km (μM)
Citations
L-tryptophan
190.0
[Batabyal07]


References

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

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

Rafice09: Rafice SA, Chauhan N, Efimov I, Basran J, Raven EL (2009). "Oxidation of L-tryptophan in biology: a comparison between tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase." Biochem Soc Trans 37(Pt 2);408-12. PMID: 19290871

Schutz72: Schutz G, Feigelson P (1972). "Purification and properties of rat liver tryptophan oxygenase." J Biol Chem 247(17);5327-32. PMID: 4626718


Report Errors or Provide Feedback
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 SRI International Pathway Tools version 18.5 on Mon Dec 22, 2014, biocyc11.