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

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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.

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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

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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.

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  1. School of Biomedical Sciences, Institute of Cell Signalling, The University of Nottingham, Nottingham, NG7 2UH, UK

    Amos A. Fatokun

  2. Molecular Immunopathology Unit, Discipline of Pathology, School of Medical Sciences, The University of Sydney, Sydney, NSW, 2006, Australia

    Nicholas H. Hunt & Helen J. Ball

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  1. Amos A. Fatokun
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  2. Nicholas H. Hunt
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  3. Helen J. Ball
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Correspondence to Helen J. Ball.

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Fatokun, A.A., Hunt, N.H. & Ball, H.J. Indoleamine 2,3-dioxygenase 2 (IDO2) and the kynurenine pathway: characteristics and potential roles in health and disease. Amino Acids 45, 1319–1329 (2013). https://doi.org/10.1007/s00726-013-1602-1

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  • DOI: https://doi.org/10.1007/s00726-013-1602-1

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