Electron Transport Chain (ETC)

Glycolysis, the link reaction and the Krebs cycle between them generate a large pool of reduced coenzymes -- $NADH+H^+$ and $FADH_2$ -- and it is the electron transport chain (ETC), located on the folded cristae of the inner mitochondrial membrane, that finally uses these to build most of respiration's ATP, in a process called terminal oxidation. According to Peter Mitchell's Chemiosmotic Theory (for which he won the 1978 Nobel Prize in Chemistry), electron transport through the chain is tightly coupled to ATP synthesis via a proton gradient. Electrons and protons pass through four sequential multiprotein complexes: Complex I (NADH dehydrogenase), containing a flavoprotein (FMN) and an iron-sulphur protein, passes electrons and protons from matrix NADH to ubiquinone (UQ, also called Coenzyme Q -- a small, lipid-soluble mobile carrier within the inner membrane); Complex II (succinate dehydrogenase), also carrying FAD and an iron-sulphur protein, receives electrons directly from succinate as it is converted to fumarate in the Krebs cycle and passes them likewise to ubiquinone ($\text{Succinate} + UQ \rightarrow \text{Fumarate} + UQH_2$); Complex III (cytochrome bc1 complex) oxidises the reduced ubiquinone (ubiquinol) and passes its electrons via an iron-sulphur centre to cytochrome c, a small mobile protein carrier attached to the outer face of the inner membrane ($UQH_2 + 2\,Cyt\,c_{ox} \rightarrow UQ + 2\,Cyt\,c_{red} + 2H^+$); and Complex IV (cytochrome c oxidase), containing two copper centres and cytochromes a and a3, is the terminal oxidase that finally reduces half a molecule of O2 to water, consuming two protons in the process ($2\,Cyt\,c_{ox} + 2H^+ + \tfrac{1}{2}O_2 \rightarrow 2\,Cyt\,c_{red} + H_2O$). This electron flow from NADH through Complexes I-IV to oxygen is coupled to ATP synthesis (oxidative phosphorylation) by the F0F1-ATP synthase, also called Complex V: its F1 head, attached to the matrix side of the inner membrane, actually converts ADP and Pi to ATP, while its F0 portion embedded in the membrane forms the channel through which protons re-enter the matrix, driving F1's rotation. Oxidising one molecule of matrix $NADH+H^+$ yields 3 ATP, and one $FADH_2$ yields 2 ATP; but NADH generated in the cytoplasm during glycolysis cannot cross the inner membrane directly, and is instead re-oxidised by an external NADH dehydrogenase present (in plants) on the outer face of the inner membrane, yielding only 2 ATP per cytosolic NADH rather than 3 -- so the two cytosolic $NADH+H^+$ from glycolysis contribute $2 \times 2 = 4$ ATP instead of the 6 ATP they would have given inside the matrix. A newer 'recent view' recalculates the true cost of transporting ATP out of the matrix into the cytosol, giving a more realistic yield of 2.5 ATP per NADH and 1.5 ATP per FADH2 -- under this accounting, plant cells net about 30 ATP for the complete aerobic oxidation of one glucose molecule (versus 32 ATP in animal cells that use the malate shuttle). Several well-known poisons act specifically on this chain: 2,4-dinitrop …