Fig. 3

Main pathways for cellular energy production and molecular signal regulation. Glycolysis begins with the phosphorylation of glucose by hexokinase (HK), producing 6-phosphogluconate. Subsequently, phosphofructokinase-1 (PFK-1) converts 6-phosphofructose into 1,3-bisphosphoglycerate. In the subsequent cleavage reaction, aldolase (ALDO) cleaves 1,3-bisphosphoglycerate into two molecules of 3-phosphoglyceraldehyde. 3-phosphoglyceraldehyde is oxidized to 1,3-bisphosphoglycerate under the catalysis of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and reduced coenzyme II (NADH) is produced in the process. Thereafter, 1,3-bisphosphoglycerate is converted into 3-phosphoglycerate by phosphoglycerate kinase (PGK1), generating one molecule of ATP. 3-phosphoglycerate is then transformed into 2-phosphoglycerate by phosphoglycerate mutase (PGAM1), and then catalyzed by enolase (ENO1) to form 2-phosphoenolpyruvate. 2-phosphoenolpyruvate is ultimately converted into pyruvate under the action of pyruvate kinase (PK), releasing another molecule of ATP. Under anaerobic conditions, pyruvate is reduced to lactate by lactate dehydrogenase (LDH). Fatty acids first need to be activated into acyl-CoA (acyl-coenzyme A). After activation, the fatty acids are transferred from the cytoplasm to the mitochondrial matrix through Carnitine palmitoyltransferase I (CPT1). The fatty acids undergo a series of β-oxidation cycles, resulting in the production of acetyl-CoA and NADH. Glutamine enters the cell through ASCT2/SLC1A5 and is converted into glutamate by the deamination reaction catalyzed by glutaminase (GLS). Glutamate can be further converted into alpha-ketoglutarate (α-KG). Nutrient-derived acetyl-CoA enters the TCA cycle, which is catalyzed by enzymes such as succinate dehydrogenase (SDH), fumarate hydratase (FH), and isocitrate dehydrogenase (IDH), ultimately producing energy molecules ATP and reducing agents NADH and FADH2. NADH and FADH2 enter OXPHOS to further generate ATP. In the aforementioned process, various signaling molecules, such as AMP-activated protein kinase (AMPK), phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT), mechanistic target of rapamycin complex (mTORC), and sirtuins (SIRT), play crucial regulatory roles in controlling energy production under physiological conditions. PDH, pyruvate dehydrogenase; PDK, pyruvate dehydrogenase kinase; GDH, glutamate dehydrogenase; ACS, acyl-CoA synthetase; ACC, acetyl-CoA carboxylase; FASN, fatty acid synthase; ACLY, ATP citrate lyase