Figure 3.

Glycolysis and aerobic respiration. The first phase of glycolysis (blue box) is the destabilization of glucose, resulting in the formation of glucose 6-phosphate (Glucose-6-P), which is further processed to β-d-Fructose 1,6-bisphosphate (FBP). In the second phase of glycolysis, FBP is converted to glyceraldehyde 3-phosphate (G-3-P). In the final phase of glycolysis, G-3-P undergoes several steps to generate pyruvate and 2 ATP molecules. In the presence of sufficient oxygen, pyruvate is transported into the mitochondria where pyruvate is processed by the tricarboxylic acid (TCA) cycle that transfers electrons to the electron transport chain (ETC) for oxidative phosphorylation, which produces ~36 molecules of ATP. In contrast, anaerobic or aerobic glycolysis instead uses LDH to facilitate the conversion of pyruvate and NADH to lactate, NAD⁺, and two ATP molecules. Growth factors mediate glycolytic metabolism through activation of tyrosine kinases (such as HER2/ErbB2) and/or Akt activation. Akt activates glycolytic enzymes such as hexokinase (HK) and phosphofructokinase (PFK). In addition to activating Akt, tyrosine kinases increase the levels of peptides phosphorylated on tyrosine residues. As pyruvate kinases M2 (PKM) binds to phosphotyrosine on peptides, this subsequently results in increased binding of phosphotyrosine peptides to PKM. This binding suppresses the PKM-mediated generation of pyruvate to be used in glycolysis. Furthermore, Akt activates the mTOR pathway, thereby stimulating protein synthesis and up-regulating numerous components of the glycolytic pathway. With low levels of ATP, LKB1-activated AMPK can inhibit mTOR-dependent protein synthesis and the activation of glycolytic genes.