Figure 8

Schematic illustrations showing potential mechanisms underlying the increase in cellular ATP production by high fructose. In this scheme, high fructose upregulates both GluT2 and GluT5 expression, resulting in an increase in cellular uptake of fructose and subsequently a greater generation of pyruvate via activation of fructolysis. This high cellular level of pyruvate then enters the citric acid cycle as acetyl coenzyme to produce a greater amount of ATP via the mitochondrial respiratory chain complexes, resulting in an increase in the release of neurotransmitter. The shRNA gene silencing of the rate-limiting enzyme, ketohexokinase, blocks generation of pyruvate and the ATP synthase inhibitor, oligomycin, blunts the mitochondrial oxidative phosphorylation to prevent the high fructose-induced ATP generation.