The increase in reduced nicotinamide adenine dinucleotide (NADH) within the mitochondria has several effects. It decreases the tricarboxylic acid (TCA) cycle, fatty acid (FA) oxidation, and gluconeogenesis. NADH inhibits the isocitrate dehydrogenase reaction and the α-ketoglutarate dehydrogenase reaction, both of which are key regulated steps in the TCA cycle. NADH also promotes the reduction of oxaloacetate (OAA) to malate, reducing the availability of OAA for the condensation process with acetyl coenzyme A (CoA) in the TCA cycle and for gluconeogenesis. Additionally, the rise in NADH inhibits FA oxidation, as it requires the oxidized form of nicotinamide adenine dinucleotide (NAD+) for the 3-hydroxyacyl CoA dehydrogenase step. The decrease in FA oxidation leads to a decrease in ATP and acetyl CoA production, which is necessary for gluconeogenesis. During fasting, lipolysis is activated due to the decrease in insulin and the increase in catecholamines, which subsequently activates hormone-sensitive lipase.
RQ1.Answer = D. The rise in reduced nicotinamide adenine dinucleotide (NADH) in the mitochondria decreases the tricarboxylic acid (TCA) cycle, fatty acid (FA) oxidation, and gluconeogenesis. NADH inhibits the isocitrate dehydrogenase reaction, the key regulated step of the TCA cycle, and the αketoglutarate dehydrogenase reaction (see figure at bottom right). It also favors the reduction of oxaloacetate (OAA) to malate (not malate to OAA), decreasing the availability of OAA for condensation with acetyl coenzyme A (CoA) in the TCA cycle and for gluconeogenesis. FA oxidation requires the oxidized form of nicotinamide adenine dinucleotide (NAD+) for the 3-hydroxyacyl CoA dehydrogenase step and, thus, is inhibited by the rise in NADH. The decrease in FA oxidation decreases the production of ATP and acetyl CoA (the allosteric activator of pyruvate carboxylase) needed for gluconeogenesis. Lipolysis is activated in fasting as a consequence of the fall in insulin and the rise in catecholamines that result in activation of hormone-sensitive lipase.