Figure 3.

The main metabolic pathways in macrophages. In the cytosol, glucose is converted into L-lactate by glycolysis, in which HK, PFK1 and PK are key enzymes. In the progress of glycolysis, glucose-6-P can be shunted to PPP pathway sustaining pentose phosphates and NADPH production. Pentose phosphates are used for the synthesis of amnio acid and nucleotide, while NADPH contributes to the production of ROS and NO. Pyruvate is induced to lactate in hypoxic conditions, whereas decarboxylated into acetyl-CoA within the mitochondria in normoxic conditions. Here, acetyl-CoA enters into the TCA cycle, providing reducing agents to the ETC through OXPHOS to generate energy. Citrate, a metabolite in TCA, participates in fatty acid synthesis when exported to the cytoplasm. Acetyl-CoA produced from FAS can be transferred into mitochondria and take part in the FAO. In M1 macrophages, two breakpoints cause the production of itaconate and the accumulation of succinate that induces HIF-1α mediated upregulation of glycolysis and IL-1β production.What’s more, the production of NO inhibits ETC. M2 macrophages can obtain enough ATP from OXPHOS through the TCA cycle. As for energy gain, FAO is essential. HK, hexokinase; Glucose 6-P, glucose 6-phosphate; Fructose 6-P, fructose 6-phosphate; PFK1, 6-phosphofructokinase 1; PK, pyruvate kinase; PPP, pentose phosphate pathway; G6PD, glucose 6-phosphate dehydrogenase; iNOS, inducible nitric oxide synthase; NO, nitric oxide; ETC, electron transport chain; TCA, tricarboxylic acid; OXPHOS, oxidative phosphorylation; IDH, isocitrate dehydrogenase; NADPH, nicotinamide-adenine dinucleotide phosphate; SDH, succinate dehydrogenase; FAS, fatty acid synthesis; FAO, fatty acid oxidation; Acetyl-CoA, acetyl-Coenzyme A; IL-1β, interleukin-1β; HIF-1α, hypoxia inducible factor 1α.