Quantification of IDO1 enzyme activity in normal and malignant tissues

Lijie Zhai, Erik Ladomersky, April Bell, Corey Dussold, Krislyn Cardoza, Jun Qian, Kristen L. Lauing, Derek Alan Wainwright*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first and rate-limiting reaction of L-tryptophan (Trp) conversion into L-kynurenine (Kyn). The depletion of Trp, and the accumulation of Kyn have been proposed as mechanisms that contribute to the suppression of the immune response—primarily evidenced by in vitro study. IDO1 is therefore considered to be an immunosuppressive modulator and quantification of IDO1 metabolism may be critical to understanding its role in select immunopathologies, including autoimmune- and oncological-conditions, as well as for determining the potency of IDO1 enzyme inhibitors. Because tryptophan 2,3-dioxygenase (TDO), and to a significantly lesser extent, IDO2, also catabolize Trp into Kyn, it's important to differentiate the contribution of each enzyme to Trp catabolism and Kyn generation. Moreover, a great variety of detection methods have been developed for the quantification of Trp metabolites, but choosing the suitable protocol remains challenging. Here, we review the differential expression of IDO1/TDO/IDO2 in normal and malignant tissues, followed by a comprehensive analysis of methodologies for quantifying Trp and Kyn in vitro and in vivo, with an emphasis on the advantages/disadvantages for each application.

Original languageEnglish (US)
Title of host publicationMethods in Enzymology
PublisherAcademic Press Inc
DOIs
StatePublished - Jan 1 2019

Publication series

NameMethods in Enzymology
ISSN (Print)0076-6879
ISSN (Electronic)1557-7988

Fingerprint

Indoleamine-Pyrrole 2,3,-Dioxygenase
Kynurenine
Enzyme activity
Tryptophan
Tissue
Enzymes
Tryptophan Oxygenase
Enzyme Inhibitors
Immunosuppressive Agents
Metabolites
Metabolism
Modulators

Keywords

  • IDO
  • Kynurenine
  • Metabolism
  • TDO
  • Tryptophan

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Zhai, L., Ladomersky, E., Bell, A., Dussold, C., Cardoza, K., Qian, J., ... Wainwright, D. A. (2019). Quantification of IDO1 enzyme activity in normal and malignant tissues. In Methods in Enzymology (Methods in Enzymology). Academic Press Inc. https://doi.org/10.1016/bs.mie.2019.07.006
Zhai, Lijie ; Ladomersky, Erik ; Bell, April ; Dussold, Corey ; Cardoza, Krislyn ; Qian, Jun ; Lauing, Kristen L. ; Wainwright, Derek Alan. / Quantification of IDO1 enzyme activity in normal and malignant tissues. Methods in Enzymology. Academic Press Inc, 2019. (Methods in Enzymology).
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abstract = "Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first and rate-limiting reaction of L-tryptophan (Trp) conversion into L-kynurenine (Kyn). The depletion of Trp, and the accumulation of Kyn have been proposed as mechanisms that contribute to the suppression of the immune response—primarily evidenced by in vitro study. IDO1 is therefore considered to be an immunosuppressive modulator and quantification of IDO1 metabolism may be critical to understanding its role in select immunopathologies, including autoimmune- and oncological-conditions, as well as for determining the potency of IDO1 enzyme inhibitors. Because tryptophan 2,3-dioxygenase (TDO), and to a significantly lesser extent, IDO2, also catabolize Trp into Kyn, it's important to differentiate the contribution of each enzyme to Trp catabolism and Kyn generation. Moreover, a great variety of detection methods have been developed for the quantification of Trp metabolites, but choosing the suitable protocol remains challenging. Here, we review the differential expression of IDO1/TDO/IDO2 in normal and malignant tissues, followed by a comprehensive analysis of methodologies for quantifying Trp and Kyn in vitro and in vivo, with an emphasis on the advantages/disadvantages for each application.",
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Zhai, L, Ladomersky, E, Bell, A, Dussold, C, Cardoza, K, Qian, J, Lauing, KL & Wainwright, DA 2019, Quantification of IDO1 enzyme activity in normal and malignant tissues. in Methods in Enzymology. Methods in Enzymology, Academic Press Inc. https://doi.org/10.1016/bs.mie.2019.07.006

Quantification of IDO1 enzyme activity in normal and malignant tissues. / Zhai, Lijie; Ladomersky, Erik; Bell, April; Dussold, Corey; Cardoza, Krislyn; Qian, Jun; Lauing, Kristen L.; Wainwright, Derek Alan.

Methods in Enzymology. Academic Press Inc, 2019. (Methods in Enzymology).

Research output: Chapter in Book/Report/Conference proceedingChapter

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T1 - Quantification of IDO1 enzyme activity in normal and malignant tissues

AU - Zhai, Lijie

AU - Ladomersky, Erik

AU - Bell, April

AU - Dussold, Corey

AU - Cardoza, Krislyn

AU - Qian, Jun

AU - Lauing, Kristen L.

AU - Wainwright, Derek Alan

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PB - Academic Press Inc

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Zhai L, Ladomersky E, Bell A, Dussold C, Cardoza K, Qian J et al. Quantification of IDO1 enzyme activity in normal and malignant tissues. In Methods in Enzymology. Academic Press Inc. 2019. (Methods in Enzymology). https://doi.org/10.1016/bs.mie.2019.07.006