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Tryptophan and Cell Death

  • Chapter
Tryptophan Metabolism: Implications for Biological Processes, Health and Disease

Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

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Abstract

Cell death attributed to the tryptophan (Trp) metabolites is dependent on the exposure time and intracellular concentrations of cytotoxic Trp derivatives such as 3-hydroxykynurenine (3HK), 3-hydroxyanthranilic acid (3HAA), 5-hydroxyanthranilic acid (5HAA), and quinolinic acid (QA). However, 3HAA, 3HK, and QA at low concentrations may also serve as a precursor for nicotinamide adenine dinucleotide [NAD+] which has vital importance to maintain cell viability. Inhibition of indoleamine 2,3-dioxygenase (IDO) activity results in a dose-dependent decrease in intracellular [NAD+] levels. Mitochondrial permeability transition occurs in several forms of necrotic cell death. Disturbances in the normal function of the mitochondria are associated with the alterations in the balance of Trp metabolism. While kynurenic acid (KA) has proven to be neuroprotective with the potential endogenous antioxidant properties, QA is a specific agonist at the N-methyl-d-aspartate (NMDA) receptors and a potent neurotoxin with the marked free radical-producing property. QA-induced cytotoxic effects are mediated by overactivation of NMDA-like receptors and overexpression of inducible nitric oxide synthase (iNOS). l-Kynurenine-derived neurotoxin-induced apoptosis occurs through reactive oxygen species (ROS)-mediated pathways and is blocked by antioxidants. Unlike the kynurenine pathway, the methoxyindole metabolites of Trp metabolism protect cells against oxidative stress-induced apoptosis. Furthermore, deprivation of Trp triggers autophagy in a mammalian target of rapamycin (mTOR)-dependent manner. mTOR inhibition can suppress the activation of cyclin-dependent kinases and then inhibits the cell cycle progress, suppresses cell proliferation, and finally results in cell apoptosis.

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Authors and Affiliations

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

    Atilla Engin M.D., Ph.D.

  2. Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey

    Atilla Engin M.D., Ph.D.

  3. Faculty of Pharmacy, Department of Toxicology, Gazi University, 06330, Hipodrom, Ankara, Turkey

    Ayse Basak Engin Ph.D.

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  1. Atilla Engin M.D., Ph.D.
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Correspondence to Atilla Engin M.D., Ph.D. .

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

    Atilla Engin

  2. Faculty of Pharmacy, Department of Toxicology, Gazi University, Hipodrom, Ankara, Turkey

    Ayse Basak Engin

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Engin, A., Engin, A.B. (2015). Tryptophan and Cell Death. In: Engin, A., Engin, A. (eds) Tryptophan Metabolism: Implications for Biological Processes, Health and Disease. Molecular and Integrative Toxicology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-15630-9_2

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