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Electron Transport Chain _ETC Energy-rich molecules, such as glucose, are metabolized by a series of oxidation reactions ultimately yielding Co2 and water. The metabolic intermediates of these reactions donate electrons to specific coenzymes ( NAD+,FAD) and The reduced form of these coenzymes ( NADH,FADH2) can, in turn, each donate a pair of electrons to a specialized set of electron carriers, collectively called the electron transport chain, as electrons are passed down the electron transport chain, they lose much of their free energy. Part of this energy can be captured and stored by the production of ATP from ADP and inorganic phosphate (Pi). This process is called oxidative phosphorylation. The remainder of the free energy that not trapped as ATP is released as heat. ETC is a chain of protein (enzyme) complexes embedded in the inner mitochondrial membrane, called complexes I, II, III, IV, and V. Complexes I to IV transports electrons and pumps hydrogen ions into the inter membrane space to create a gradient,whereas complex V catalyzes ATP synthesis as figure below reveals. 1 Each complex accepts or donates electrons to relatively mobile electron carriers, such as ubiquinone (coenzyme Q) and cytochrome c. Each carrier in the electron transport chain can receive electrons from an electron donor, and can subsequently donate electrons to the next carrier in the chain. The electrons ultimately combine with oxygen (final electron acceptor) and protons to form water. These complexes are: Complex I; NADH-CoQ reductase (NADH dehydrogenase complex) Complex II; Succinate-Q-reductase Complex III; cytochrome reductase Complex IV; cytochrome oxidase 2 Complex V; ATP synthase F0 Proton pump and ATP synthesis The energy of electron transfer is used to drive protons out of the matrix by the complexes I, III and IV that are proton pumps. The proton pumps (complexes I, III and IV) expel H+ from inside to outside of the inner membrane. So, there is high H+ concentration outside the inner membrane. This causes H+ to enter into mitochondria through the channels (Fo); this proton influx causes ATP synthesis by ATP synthase. Energy yield (number of ATP generated) per molecule of glucose when it is completely oxidized through glycolysis plus citric acid cycle, under aerobic conditions is demonstrated below 3 Only 4 of 38 ATP ultimately produced by respiration of glucose are derived from substrate-level phosphorylation (2 from glycolysis and 2 from Krebs Cycle).The vast majority of the ATP (90%) comes from the energy in the electrons carried by NADH and FADH2 . Inhibitors of ETC and oxidative phosphorylation This has provided knowledge about the mechanism of action of several poisons 1. Complex I to Co-Q specific inhibitors i. Insecticide and fish poison ii. Barbiturates, sedative 2. Inhibitors of complex II to Co-Q i. Carboxin 4 3. Inhibitors of complex III to cytochrome c i.antidote of war gas ii. Antimycin 4. Complex IV inhibitors i. Carbon monoxide ii. Cyanide (CN–) iii. Azide (N3–) iv. Hydrogen sulphide (H2S) 5. Inhibitors of oxidative phosphorylation i. Oligomycin, inhibits flow of protons through Fo Uncouplers of Oxidative Phosphorylation Uncouplers will allow oxidation to proceed, but the energy instead of being trapped by phosphorylation is dissipated as heat. This is achieved by removal of the proton gradient. The uncoupling of oxidative phosphorylation is useful biologically as in hibernating animals and in newborn human infants, the liberation of heat energy is required to maintain body temperature. In Brown adipose tissue, thermogenesis is achieved by this process. Uncouplers i. 2,4-dinitrophenol (2,4-DNP) ii. 2,4-dinitrocresol (2,4-DNC) Physiological Uncouplers i.Thyroxin, in high doses ii. Thermogenin in brown adipose tissue 5