Figure 1:

Fructose metabolism results in intracellular ATP depletion and triggers a survival response. (A) The metabolism of fructose by fructokinase (FK) results in rapid ATP consumption with a fall in ATP and intracellular phosphate (Pi) in the cell. The low intracellular phosphate activates the enzyme AMP deaminase-2 (AMPD2) which removes the AMP substrate to make inosine monophosphate (IMP) and eventually uric acid. The rise in intracellular uric acid results in the translocation of the NADPH oxidase to the mitochondria resulting in oxidative stress that suppresses oxidative phosphorylation. This is also associated with an increase in lipogenesis and a block in fatty acid oxidation. (B) As ATP levels fall, the survival response is stimulated as noted by hunger, foraging, excessive food intake, reduced resting energy metabolism, fat storage, insulin resistance, systemic inflammation and hypertension.