Figure 2 Metabolic reprogramming of immune cells upon activation Figure 2 | Metabolic reprogramming of immune cells upon activation. During inflammation, immune cells are activated and convert from a resting state into an effector mode, reprogramming their metabolism to aerobic glycolysis. An increase in glucose transportation into the cell drives elevated glycolytic activity, causing excessive availability of glycolytic intermediates, which serve as precursor molecules for biosynthetic processes. For example, glucose 6-phosphate (generated by the first step in glycolysis) can feed into the pentose phosphate pathway (PPP), supporting nucleotide synthesis and the generation of NADPH. Another example is cytoplasmic acetyl-CoA (generated from glucose via pyruvate), which supports the production of cholesterol and fatty acids for lipid synthesis. Of note, many pyruvate molecules are converted to lactate, which is secreted from cells and can substantially affect the pH of the surrounding milieu. Although aerobic glycolysis is an inefficient way to generate ATP (creating only two molecules of ATP per molecule of glucose), high rates of flux through this pathway enables energy homeostasis to be sustained, even when mitochondrial ATP synthesis is impaired. Alternative fuels such as glutamine feed into the tricarboxylic acid (TCA) cycle and supply biomolecules for biosynthetic processes. ETC, electron transport chain; GLUT1, glucose transporter type 1. Gaber, T. et al. (2017) Metabolic regulation of inflammation Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2017.37