Electron Transport Chain and Oxidative Phosphorylation

Wherever NADH+H⁺ and FADH₂ are produced - during glycolysis, the connecting-link reaction, and the Krebs cycle - they are ultimately re-oxidised with the help of a series of electron carriers and enzymes known as the electron transport chain (ETC), or electron transport system (ETS). These carriers and enzymes are arranged, as a series of complexes labelled Complex I, II, III, IV and V, on the inner mitochondrial membrane (Fig. 13.2).

NADH+H⁺ is oxidised by NADH dehydrogenase (Complex I), and its electrons are transferred to ubiquinone (coenzyme Q, or CoQ), which sits in the inner mitochondrial membrane; once reduced, CoQ is called ubiquinol. FADH₂ is oxidised by Complex II (succinate dehydrogenase), and these electrons are also fed into CoQ. During the oxidation of both NADH+H⁺ and FADH₂, protons and electrons are both released, but only the electrons are carried onward along the chain - the protons are instead pumped out into the outer chamber of the mitochondrion.

Ubiquinol is then oxidised by Complex III (the cytochrome bc1 complex), and its electrons are transferred to cytochrome C - a small, iron-containing protein loosely associated with the inner membrane, which acts as a mobile electron carrier shuttling electrons between Complex III and Complex IV. Cytochrome C is in turn oxidised by Complex IV (cytochrome C oxidase, made up of cytochromes a and a3), which transfers the electrons to molecular oxygen - the terminal oxidation step of respiration. The reduced oxygen then combines with protons to form a molecule of water.

The protons needed for this final step, and pumped out earlier into the outer chamber, are channelled back into the inner chamber (matrix) through the F₀ part of the membrane-embedded oxysome, or Complex V. This proton channelling through F₀ is coupled to the catalytic F₁ head, which uses the energy of the returning proton flow to synthesise ATP from ADP and inorganic phosphate - this coupled process is oxidative phosphorylation. Because the transport of protons is directly coupled to ATP synthesis in this way, the mechanism is named chemiosmosis, a term coined by Peter Mitchell.

The oxidation of one NADH+H⁺ yields 3 ATP molecules, while the oxidation of one FADH₂ yields 2 ATP molecules - though the exact number produced can vary somewhat with physiological conditions and with which respiratory substrate is actually being oxidised.

It is worth remembering, too, that although oxygen is consumed and CO₂ released during respiration, this can give the false impression that respiratory materials unite directly with oxygen. In fact, oxygen does not play so direct a role: the primary event in respiration is the removal of hydrogen from the respiratory material, a reaction catalysed by enzymes called dehydrogenases (free hydrogen cannot exist inside the cell, so as soon as it is removed it is picked up by an acceptor coenzyme). In aerobic respiration, this hydrogen is finally handed over to oxygen at Complex IV, and the two combine to form water.

The ATP balance sheet (Table 13.3). Adding up every ATP-generating step for the complete aerobic oxidation of one glucose molecule: glycolysis consumes 2 ATP and produces 4 ATP by substrate-level phosphorylation plus 6 ATP from its 2 NADH+H⁺ (each worth 3 ATP) by oxidative phosphorylation, a step total of 10 ATP (net 8 after the 2 consumed); the conversion of the 2 pyruvate molecules to acetyl-CoA produces 6 ATP from their 2 NADH+H⁺ by oxidative phosphorylation; and the Krebs cycle (which turns twice per glucose) produces 2 ATP by substrate-level phosphorylation (2 GTP) plus 18 ATP from its 6 NADH+H⁺ and 4 ATP from its 2 FADH₂ by oxidative phosphorylation, a step total of 24 ATP. Summed across all three stages, this gives 2 ATP consumed, 6 ATP by substrate-level phosphorylation, and 34 ATP by oxidative phosphorylation (30 from NADH+H⁺ and 4 from FADH₂) - a gross total of 40 ATP, and, after subtracting the 2 ATP consumed early in glycolysis, a final net gain of 38 ATP per glucose molecule. …