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Amino Acids

, Volume 45, Issue 6, pp 1319–1329 | Cite as

Indoleamine 2,3-dioxygenase 2 (IDO2) and the kynurenine pathway: characteristics and potential roles in health and disease

  • Amos A. Fatokun
  • Nicholas H. Hunt
  • Helen J. Ball
Minireview Article

Abstract

The kynurenine pathway is the major route for the oxidative degradation of the amino acid tryptophan. Activity of the pathway is involved in several disease conditions, both in the periphery and the central nervous system, including cancer, inflammatory disorders, neurological conditions, psychiatric disorders and neurodegenerative diseases. Three enzymes are now known to catalyze the first and rate-limiting step in the catabolism of tryptophan along this pathway: tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO, subsequently named IDO1), both of which have been extensively studied, and a third enzyme, indoleamine 2,3-dioxygenase 2 (IDO2), a relative newcomer to the kynurenine pathway field. The adjuvant chemotherapeutic agent, 1-methyl-d-tryptophan, was intially suggested to target IDO2, implying involvement of IDO2 in tumorigenesis. Subsequently this compound has been suggested to have alternative actions and the physiological and pathophysiological roles of IDO2 are unclear. Targeted genetic interventions and selective inhibitors provide approaches for investigating the biology of IDO2. This review focuses on the current knowledge of IDO2 biology and discusses tools that will assist in further characterizing the enzymes of the kynurenine pathway.

Keywords

Kynurenine pathway Tryptophan Indoleamine 2,3-dioxygenase Tryptophan 2,3-dioxygenase 1-Methyltryptophan 

Abbreviations

CNS

Central nervous system

IDO

Indoleamine 2,3-dioxygenase

IFN-γ

Interferon-γ

LIP

Liver-enriched inhibitory protein

MB

Methylene blue

1DMT

1-Methyl-d-tryptophan

1LMT

1-Methyl-l-tryptophan

1MT

1-Methyltryptophan

NMDA

N-Methyl-d-aspartate

NAD+

Nicotinamide adenine dinucleotide

rmIDO

Recombinant mouse indoleamine 2,3-dioxygenase

rhIDO

Recombinant human indoleamine 2,3-dioxygenase

TDO

Tryptophan 2,3-dioxygenase

l-Trp

l-Tryptophan

Notes

Acknowledgments

Dr. Fatokun was funded by an International Visiting Research Fellowship (IVRF) Award from the University of Sydney, Australia, and was a Visiting Fellow (from the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA) in the laboratory of Prof. Nicholas Hunt. The work was supported by grants from the Australian Research Council and National Health and Medical Research Council of Australia to NH and HB.

Conflict of interest

None.

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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Amos A. Fatokun
    • 1
  • Nicholas H. Hunt
    • 2
  • Helen J. Ball
    • 2
  1. 1.School of Biomedical Sciences, Institute of Cell SignallingThe University of NottinghamNottinghamUK
  2. 2.Molecular Immunopathology Unit, Discipline of Pathology, School of Medical SciencesThe University of SydneySydneyAustralia

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