Fig. 3
M1/M2 macrophage metabolic signaling pathways and immune regulation. M1 macrophage is featured by aerobic glycolysis, which leads to lactate development. The ROS and NO are produced accordingly. The PPP produces NADPH correlated with arginine synthesis and the aspartate-arginosuccinate shunt pathway (AASS). In addition, the tricarboxylic acid cycle (TCA) produces essential citrate and succinate vital to the metabolism of fatty acids and the stabilization of HIF-1α, leading to the transcription of pro-inflammatory and glycolytic genes and epigenetic alterations. On the other hand, M2 macrophage primarily generates ATP in an oxidative TCA cycle, combined with OXPHOS. This also metabolizes arginine. Similarly, the process depends on the energy sources of β-oxidation and glutamine metabolism. Also, precise signaling and immune regulation are vital in metabolic pathways, including aerobic glycolysis leading to lactate, NO, fatty acid synthesis, and glutamine pathways. Equally, acetyl-CoA, citrate, itaconate, and succinate are involved in immune regulation in the TCA cycle. Similarly, hexokinase 2 (HK-II), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and arginase 1 play their roles in immune regulation. All enzymes are shown in orange. GLUT1 glucose transporter 1, NOX2 NADPH oxidase 2, iNOS inducible nitric oxide synthase, HK hexokinase, PFK1 phosphofructo-1-kinase, PFK2 phosphofructokinase-2, LDHA lactate dehydrogenase A, MCT4 monocarboxylate transporter 4, ME1 malic enzyme, ACLY ATP-citrate lyase, FA fatty acids, FAS: fatty acid synthase, CIC citrate carrier, PDH pyruvate dehydrogenase, MDH malate dehydrogenase, FH fumarate hydratase, SDH succinate dehydrogenase, CII complex II, CAD cis-aconitate decarboxylase, ACO2 aconitase 2, IDH isocitrate dehydrogenase, SLC3a2 solute carrier family 3 member 2, LAL lysosomal acid lipase, CPT-1 carnitine palmitoyltransferase I, CD36 cluster of differentiation 36
