Tryptophan and Cell Death

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 dosedependent 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 specifi c 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 fi nally results in cell apoptosis.

Saccharomyces cerevisiae and Torulaspora delbrueckii Intra- and Extra-Cellular Aromatic Amino Acids Metabolism

“…Via the Ehrlich pathway, the amino acids TRP, PHE, and TYR produce the aromatic higher alcohols TOL, phenylethanol, and tyrosol (TYL), respectively. The biosynthesis of these compounds is positively correlated with ethanol stress-tolerant yeasts that have an enhanced expression of genes related to TRP metabolism . These compounds, as autoinducers, are able to transmit information about the population density and the amount of available nitrogen. , Excessive concentration of these higher alcohols can result in a strong, pungent smell and taste, whereas optimal levels have a positive impact, producing wines with a flowery character .…”

“…These compounds, as autoinducers, are able to transmit information about the population density and the amount of available nitrogen. , Excessive concentration of these higher alcohols can result in a strong, pungent smell and taste, whereas optimal levels have a positive impact, producing wines with a flowery character . Moreover, through the TRP pathway, yeast contributes to wine aroma directly by biotransforming odorless metabolites into flavor-active compounds, such as methyl mercaptan and indole, and indirectly via chemical reactions during wine aging, since the indolic metabolites are putative precursors of other aromatic substances, like 2-aminoacetophenon (2AA; Figure ). In addition, indoles can react with the SO 2 , when added to wine for protection against oxygen and microorganisms, delivering sulfonated metabolites and effecting wine shelf life and a metabolic fingerprint …”