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The NADH, H+, and FADH2 that accumulate as the TCA cycle operates form an enormous potential en­ergy pool.

The reduced coenzymes are reoxidized and transfer their reducing capabilities through a se­quence of compounds to oxygen, which accepts elec­trons and H+ to form water.

The sequence of carriers through which the electrons and H + pass is called the electron transport system.

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Each transfer of elec­trons (or H+) from one compound to the next results, in the oxidation (electron loss) by the donor molecule and the reduction (electron gain) by the acceptor mol­ecule.

Such a transfer occurred in reaction 16-3 in the matrix during pyruvate dehydrogenase action. The enzyme-linked FAD (E3-FAD) accepted the electrons from the substrate and was reduced, thereby forming E3

FADH2. Subsequently, the E3-FADH2 transferred hydrogens and electrons to NAD+, which therefore was reduced while the FADH2 was reoxidized (Fig. 16-21).

Sequential Reduction and Oxidation of FAD linked to E3

In the electron transport system the electrons are shuttled from one to another of about 12 to 17 inter­mediate compounds before they eventually reach oxy­gen to form water. Although it is possible to directly reoxidize NADH with oxygen, in the mitochondria this is usually prevented.

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The enzymes of the electron transport system appear to be arranged in the inner membrane in such a manner that the transfer of the electrons must proceed through the specified series of intermediates. An energy change occurs during elec­tron transfer; a proton gradient and membrane poten­tial are ultimately created across the inner mem­brane. The proton gradient and membrane potential provide the energy to phosphorylate ADP—a process termed oxidative phosphorylation.