Metabolic pathways match T cells’ functional demands. Schematic diagrams of metabolic pathways employed by T cells at different stages of activation and differentiation. Dominant pathways are indicated as red cascades. Blue arrows show pathways that are used at a steady level, and dashed arrows indicate pathways that might be utilized but are insufficiently investigated. (Left) Resting lymphocytes generate energy from glucose, fatty acids and amino acids. Most ATP is produced in mitochondria by fermentation of acetyl-coenzyme A (CoA) in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). (Middle) Effector lymphocytes (activated lymphocytes) swiftly and massively upregulate glycolysis and glutaminolysis, while keeping the TCA cycle low. These cells switch lipid metabolism from beta-oxidation towards fatty acid synthesis (lipogenesis). (Right) Memory lymphocytes mainly use beta-oxidation to support their energy needs. 3PG, 3-phosphoglycerate; FFA, free fatty acid; G-6-P, glucose-6-phosphate; NADPH, nicotinamide adenine dinucleotide phosphate; PPP, pentose phosphate pathway; R-5-P, ribose 5-phosphate.