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Metabolic regulation of immune responses: therapeutic opportunities
Nadine Assmann, David K. Finlay
Nadine Assmann, David K. Finlay
Published June 1, 2016
Citation Information: J Clin Invest. 2016;126(6):2031-2039. https://doi.org/10.1172/JCI83005.
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Review

Metabolic regulation of immune responses: therapeutic opportunities

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Abstract

Immune cell metabolism is dynamically regulated in parallel with the substantial changes in cellular function that accompany immune cell activation. While these changes in metabolism are important for facilitating the increased energetic and biosynthetic demands of activated cells, immune cell metabolism also has direct roles in controlling the functions of immune cells and shaping the immune response. A theme is emerging wherein nutrients, metabolic enzymes, and metabolites can act as an extension of the established immune signal transduction pathways, thereby adding an extra layer of complexity to the regulation of immunity. This Review will outline the metabolic configurations adopted by different immune cell subsets, describe the emerging roles for metabolic enzymes and metabolites in the control of immune cell function, and discuss the therapeutic implications of this emerging immune regulatory axis.

Authors

Nadine Assmann, David K. Finlay

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Figure 1

Glucose can be used for ATP synthesis and cellular biosynthesis.

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Glucose can be used for ATP synthesis and cellular biosynthesis.
ATP is ...
ATP is the key molecule that provides energy for cellular processes. Glucose can be metabolized via two integrated metabolic pathways, glycolysis and OxPhos, which efficiently convert glucose into ATP. Glycolysis converts glucose to pyruvate in the cytosol, generating two molecules of ATP. In the mitochondria, pyruvate is further metabolized to CO2 by the KREBS cycle, which drives OxPhos and ATP synthase activity, generating up to 34 ATP per molecule of glucose. Cells can also metabolize alternative substrates, such as lipids and glutamine, which feed into the KREBS cycle to drive OxPhos and ATP synthesis. Aerobic glycolysis supports biosynthetic processes, as it allows the uptake of larger amounts of glucose and the maintenance of elevated glycolytic flux. Glycolytic intermediates are then diverted into other pathways for synthesis of biomolecules that support biosynthetic processes. For instance, glucose-6-phosphate (G6P) can feed into the pentose phosphate pathway (PPP), generating ribulose-5-phosphate (R5P) to support nucleotide synthesis. This pathway also generates NADPH, a cofactor that is essential for various biosynthetic processes, including lipid synthesis. Glucose can also be converted into cytoplasmic acetyl-CoA via citrate in the KREBS cycle for the production of cholesterol and fatty acids. Glycolytic intermediates are also converted into other biomolecules for protein and lipid synthesis. Glutamine feeds into the KREBS cycle and can also supply biomolecules for biosynthetic processes under certain conditions. F6P, fructose-6-phosphate; DHAP, dihydroxyacetone phosphate; G3P, glyceraldehyde 3-phosphate; BPG, 2,3-bisphosphoglycerate; GP, glycerate 3-phosphate; OAA, oxaloacetate.

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