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Metabolic Stress and Immunity: Nutrient-Sensing Kinases and Tryptophan Metabolism

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Protein Kinase-mediated Decisions Between Life and Death

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1275))

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Abstract

The tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO-1) has gained major attention due the immunoregulatory nature of this pathway. Both depletion of tryptophan concentrations as well as the accumulation of downstream metabolites are relevant for the mediation of the manifold consequences of increased tryptophan metabolism. Increased tryptophan catabolism is indicative for several chronic inflammatory disorders such as infections, autoimmune diseases or cancer. Low tryptophan availability is likely to be involved in the manifestation of a variety of comorbidities such as anemia, cachexia, depression and neurocognitive disturbances.

Several nutrient sensing kinases are implicated in the downstream effects of dysregulated tryptophan metabolism. These include mechanisms that were conserved during evolution but have gained special features in multicellular eukaryotes, such as pathways regulated by eukaryotic translation initiation factor 2 (eIF-2)-alpha kinase (GCN2, also named general control nonderepressible 2 kinase), 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and target of rapamycin (TOR).

The interplay between IDO-1 and above-mentioned pathway seems to be highly context dependent. A better understanding of the crosstalk is necessary to support the search for druggable targets for the treatment of inflammatory and autoimmune disorders.

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Authors and Affiliations

  1. Institute of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria

    Johanna M. Gostner

  2. Institute of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria

    Dietmar Fuchs

  3. Department of Internal Medicine II, Infectious Diseases, Pneumology, Rheumatology, Medical University of Innsbruck, Innsbruck, Austria

    Katharina Kurz

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  1. Johanna M. Gostner
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  2. Dietmar Fuchs
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  3. Katharina Kurz
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Correspondence to Katharina Kurz .

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  1. Department of Toxicology, Faculty of Pharmacy, Gazi University, Ankara, Turkey

    Ayse Basak Engin

  2. Department of General Surgery, Faculty of Medicine, Gazi University, Ankara, Turkey

    Atilla Engin

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Gostner, J.M., Fuchs, D., Kurz, K. (2021). Metabolic Stress and Immunity: Nutrient-Sensing Kinases and Tryptophan Metabolism. In: Engin, A.B., Engin, A. (eds) Protein Kinase-mediated Decisions Between Life and Death. Advances in Experimental Medicine and Biology, vol 1275. Springer, Cham. https://doi.org/10.1007/978-3-030-49844-3_16

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