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| Figure 4: The metabolic stress in AD and the failure in the cholinergic system (simplified pathways) in a cholinergic neuron. On the left, a normal mitochondrion is depicted having a normal glycolysis that provides ATP and a normal oxidative Krebs cycle (=TCA) that provides GTP. The oxidation of NADH + and FADH + is expected to provides ATP molecules during oxidative phosphorylation (large arrow) within the mitochondrion. Beta-oxidation of fatty acid molecules is another common way to AcetylCoA and it has not been depicted. It requiers NAD + and FAD to function, hence this pathway is impaired in AD. On the right, during the Warburg effect, the conversion of pyruvate into lactate recyles NAD + to maintain glycolysis despite the mitochondrial dysfunction (and the related impaired NADH 2--NAD + interconversion). Indeed, according to the AD Gas Model, oxygen bubbles are depicted standing on Complexes I and IV, leading to complex dysfunctions and impairment of NADH + oxidation to NAD +. The figure is not as neat as it could be, since within the neuron, the energy supply mainly involves lactate rather than glucose, lactate being provided by the nearby astrocyte (the astrocyte-neuron lactate shuttle model is not depicted). |
