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===Aerobic regeneration of NAD<sup>+</sup> and further catabolism of pyruvate=== In [[aerobic organism|aerobic]] [[eukaryote]]s, a complex mechanism has developed to use the oxygen in air as the final electron acceptor, in a process called [[oxidative phosphorylation]]. [[aerobic organism|Aerobic]] [[prokaryotes]], which lack mitochondria, use a variety of [[Oxidative phosphorylation#Prokaryotic electron transport chains|simpler mechanisms]]. * Firstly, the [[Nicotinamide adenine dinucleotide|NADH + H<sup>+</sup>]] generated by glycolysis has to be transferred to the mitochondrion to be oxidized, and thus to regenerate the NAD<sup>+</sup> necessary for glycolysis to continue. However the inner mitochondrial membrane is impermeable to NADH and NAD<sup>+</sup>.<ref name=stryer5>{{cite book | vauthors = Stryer L | title = Biochemistry |chapter= Oxidative phosphorylation. |edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |pages= 537β549 |isbn= 0-7167-2009-4 }}</ref> Use is therefore made of two "shuttles" to transport the electrons from NADH across the mitochondrial membrane. They are the [[malate-aspartate shuttle]] and the [[glycerol phosphate shuttle]]. In the former the electrons from NADH are transferred to cytosolic [[Oxaloacetic acid|oxaloacetate]] to form [[Malic acid|malate]]. The malate then traverses the inner mitochondrial membrane into the mitochondrial matrix, where it is reoxidized by NAD<sup>+</sup> forming intra-mitochondrial oxaloacetate and NADH. The oxaloacetate is then re-cycled to the cytosol via its conversion to aspartate which is readily transported out of the mitochondrion. In the glycerol phosphate shuttle electrons from cytosolic NADH are transferred to [[dihydroxyacetone]] to form [[glycerol-3-phosphate]] which readily traverses the outer mitochondrial membrane. Glycerol-3-phosphate is then reoxidized to dihydroxyacetone, donating its electrons to [[Flavin adenine dinucleotide|FAD]] instead of NAD<sup>+</sup>.<ref name=stryer5 /> This reaction takes place on the inner mitochondrial membrane, allowing FADH<sub>2</sub> to donate its electrons directly to coenzyme Q ([[ubiquinone]]) which is part of the [[electron transport chain]] which ultimately transfers electrons to molecular oxygen {{chem2|O2}}, with the formation of water, and the release of energy eventually captured in the form of [[Adenosine triphosphate|ATP]]. * The glycolytic end-product, pyruvate (plus NAD<sup>+</sup>) is converted to [[acetyl-CoA]], {{chem2|CO2}} and NADH + H<sup>+</sup> within the [[mitochondria]] in a process called [[pyruvate decarboxylation]]. * The resulting acetyl-CoA enters the [[citric acid cycle]] (or Krebs Cycle), where the acetyl group of the acetyl-CoA is converted into carbon dioxide by two decarboxylation reactions with the formation of yet more intra-mitochondrial NADH + H<sup>+</sup>. * The intra-mitochondrial NADH + H<sup>+</sup> is oxidized to NAD<sup>+</sup> by the [[electron transport chain]], using oxygen as the final electron acceptor to form water. The energy released during this process is used to create a hydrogen ion (or proton) gradient across the [[inner membrane of the mitochondrion]]. * Finally, the proton gradient is used to produce about 2.5 [[Adenosine triphosphate|ATP]] for every NADH + H<sup>+</sup> oxidized in a process called [[oxidative phosphorylation]].<ref name=stryer5 />
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