Journal of Biological Chemistry, Год журнала: 2023, Номер 299(6), С. 104827 - 104827

Опубликована: Май 23, 2023

Regulated tryptophan metabolism by immune cells has been associated with the promotion of tolerance and poor outcomes in cancer. The main focus research centered on local depletion IDO1, an intracellular heme-dependent oxidase that converts to formyl-kynurenine. This is first step a complex pathway supplying metabolites for de novo NAD+ biosynthesis, 1-carbon metabolism, myriad kynurenine derivatives which several act as agonists arylhydrocarbon receptor (AhR). Thus, express IDO1 deplete while generating downstream metabolites. We now know another enzyme, secreted L-amino acid IL4i1 also generates bioactive from tryptophan. In tumor microenvironments, have overlapping expression patterns, especially myeloid cells, suggesting two enzymes control network tryptophan-specific metabolic events. New findings about shown both generate suite suppress oxidative cell death ferroptosis. within inflammatory environments, simultaneously essential amino depletion, AhR activation, suppression ferroptosis, biosynthesis key intermediates. Here, we summarize recent advances this field, focusing speculate inhibition remains viable adjuvant therapy solid tumors, effects must be accounted for, potentially may need inhibited at same time produce positive cancer therapy. 20 proteinogenic acids sustain cellular biochemistry by: (i) translation, (ii) source carbon skeletons nitrogen energy generation nucleotide (iii) "shuttles" move molecules different compartments tasks such malate-aspartate shuttle or methionine major methyl donor 1-carbon-folate cycle. Several dedicated additional functions precursors signaling (neurotransmitters), cofactors (heme, glycine), redox protective glutathione (from glycine, cysteine, glutamate). Because these diverse functions, balance their sources synthesis, transport, scavenging protein sinks therefore constantly monitor deficiencies excesses all acids. An facet concerns biochemical where regulated enzyme consumes distinct products. setting, events occur simultaneously: can become limiting, triggering defenses including increased reduction activation autophagy (and related measures) products modulatory effects. define "regulated" here specific, induced activity metabolizing via cytokines, pathogen products, other pathways, acquisition not normally present type interest. case latter, many patterns differ origin, presumably way obtain resources growth evade control. acid-metabolizing cytokines are arginases (ARG1 cytoplasm ARG2 mitochondria), oxidases (indole, 2,3 dioxygenase), TDO2 (tryptophan dioxygenase) (Interleukin 4-induced 1, oxidase) (1Murray P.J. Amino auxotrophy system immunological nodes.Nat. Immunol. 2016; 17: 132-139Google Scholar). 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