Fig. 4 | Nature Communications

Fig. 4

From: Competition for nutrients and its role in controlling immune responses

Fig. 4

Competition for nutrients and the impact on signal transduction. Decreased levels of various nutrients within immune microenvironments could occur due to competitive uptake by surrounding cells. Alternatively, the expression of enzymes that consume nutrients, such as arginase, inducible nitric oxide synthase (iNOS) and Indoleamine-pyrrole 2,3-dioxygenase (IDO), can lead to reduced levels of arginine (Arg) and tryptophan (Trp). Limiting levels of nutrients will affect various signalling pathways. Mammalian target of rapamycin complex 1 (mTORC1) signalling is sensitive to levels of arginine, leucine (Leu) and glutamine (Gln). Glucose deprivation will also activate AMP-activated protein kinase (AMPK) due to reduced levels of ATP or fructose-1,6-bisphosphate (FBP) leading to the inhibition of mTORC1 activity. The metabolite phosphoenolpyruvate (PEP), generated when glucose is metabolised by glycolysis, can affect the duration of NFAT signalling. Gln and glucose are required for the production of uridine diphosphate N-acetylglucosamine (GlcNAc) that is important in sustaining the expression of the transcription factor cMyc. Decreased levels of amino acids in general will lead to the activation of general control nonderepressible 2 (GCN2). The product of IDO-mediated Trp metabolism, kynurenine (Kyn), can promote signalling through the aryl hydrocarbon receptor (AhR). NFAT nuclear factor of activated T cells

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