PKB/Akt phosphorylates RabGAPs (AS160/Tbc1d4, Tbc1d1) to prevent their inhibitory action (red type), increasing translocation of vesicles containing the glucose transporter GLUT4 to the membrane (blue arrow). This increases glucose uptake into the cell. Hexokinase II (HKII) converts glucose to glucose 6-phosphate (G6P). It is tethered to the mitochondrial membrane, interacting with the voltage-dependent anion channel (VDAC), allowing it to access ATP directly from the mitochondria, and facilitating direct transfer of ADP back into the mitochondria. HKII expression and activity is increased by PKB/Akt signalling (blue type) increasing production of G6P. Glycolysis (centre). G6P is converted to fructose 6-phosphate which is then converted to fructose 1,6-bisphosphate by phosphofructokinase (PFK) in the rate-limiting step of the pathway. Fructose 6-phosphate interconversion with fructose 2,6-bisphosphate is performed by the cardiac isoform of phosphofructokinase 2 (PFKB2), an enzyme with dual kinase (K) and phosphatase (P) activity. PKB/Akt phosphorylates and inhibits the phosphatase activity, resulting in accumulation of fructose 2,6-bisphosphate, an allosteric activator of PFK. This increases glycolytic flux to produce pyruvate for oxidative phosphorylation in the mitochondria. If oxidative phosphorylation is insufficient to manage additional pyruvate, pyruvate is converted to lactate by lactate dehydrogenase (LDH). This causes acidification and excess lactate is exported from the cell. Pentose phosphate pathway (left section). G6P is converted to 6-phospho-gluconolactone by G6P dehydrogenase (G6PDH), relying on production of G6P that is increased by PKB/Akt signalling. This reaction produces NADPH, required to reduce oxidised glutathione (GSSG) to GSH. GSH is a critical antioxidant in the cell, scavenging reactive oxygen species (ROS). 6-phospho-gluconolactone can be returned to the glycolytic pathway via further oxidative and non-oxidative reactions.