1. INTRODUCTION During reactions involved in fatty acid oxidation and the TCA cycle, reducing equivalents (such as electrons) are derived from sequential breakdown and oxidation of the substrates. The reducing equivalents are transferred to NADH and FADH2, which are subsequently oxidized by the electron transport chain (ETC). (ETC) is: a system of electron carriers located in the inner membrane of the mitochondria. In the presence of O2, this system converts reducing equivalents (electrons) into utilizable energy, such as ATP by the process of oxidative phosphorylation. The complete oxidation of NADH and FADH2 by the ETC results in the production of approximately 2.5 and 1.5 mol of ATP per mole of reducing equivalent transferred to O2, respectively.

2. ELECTRON TRANSPORT CHAIN DR SAMEER FATANI

3. OXIDATION-REDUCTION REACTIONS The mitochondrial electron transport chain is an example for the oxidation-reduction reactions. oxidation-reduction reactions occurs when there is a transfer of electrons from suitable electron donor to (reductant) to a suitable electron acceptor (oxidant). Two types of transferrable reducing equivalents: - In some oxidation-reduction reactions only electrons are transferred from reductant to oxidant (i.e., electron transfer between cytochromes, cytochrome c and a) - Whereas in other types of reactions, both electrons and protons (hydrogen atoms) are transferred (e.g. electron transfer between NADH and FAD: NADH + H+ + FAD ====== NAD+ + FADH2 Oxidized and reduced forms of compounds or groups operating in oxidation-reduction reactions are referred to as redox couples or pairs. Oxidation-reduction potential: the facility or how ease and readily, the given electron donor (reductant) to give up its electrons to an electron acceptor (oxidant) is expressed quantitatively as the oxidation-reduction potential of the system. Electron donor ------------------ electron acceptor Electron donor ========== electron acceptor An oxidation-reduction potential is measured in volts as an electromotive force (emf) of a half-cell made up of both members of an oxidation-reduction couple when compared to a standard reference half-cell (usually hydrogen electrode reaction). REDUCTANT of an oxidation-reduction pair with a LARGE NEGATIVE POTENTIAL will give up its electrons more READILY than redox pairs with smaller negative or positive redox potentials.

4. Compounds with large negative potentials are considered to be strong reducing agents (i.e. strongly donate and give up its electrons to another compound which will be in reduced form). By contrast, a strong oxidant (e.g. characterized by a large positive potential) has a very high affinity for electrons and will act to oxidize compounds with more negative standard potentials. THE NERNEST EQUATION: characterizes the relationship between standard oxidation- reduction potential of a particular redox pair, observed potential, and ratio of concentrations of oxidant and reductant in the system. Midpoint potential: occurs when: Observed potential = the standard potential In this case also, concentration of oxidant = concentration of reductant

5. Free-Energy Changes in Redox Reactions Oxidation-reduction potential differences between two redox pairs are similar to free-energy changes in chemical reactions, in that both quantities depend on concentration of reactants and products of the reaction and the following relationship exists: ΔG01 = - nf ΔE Using this expression. The free-energy change for electron transfer reactions can be calculated if the potential difference between two oxidation-reduction pairs is known. Hence, for the mitochondrial electron transfer process in which electrons are transferred between the NAD+ - NADH couple (E = -0.32 V) and the 1l2O2-H2O couple (E = + 0.82 V), the free-energy change for this process can be calculated: ΔG = -nf ΔE = -2 X 96.5 KJ v -1 X 1.14 V ΔG = -219 kJ mol-1. Where 96.5 is the Faraday constant in KJ V-1 and n is number of electrons transferred; for example, in the case of NADH → O2, n=2.

6. The free energy available from the potential span between NADH and O2 in the electron transfer chain is capable of generating more than enough energy to synthesize three molecules of ATP per two reducing equivalents or two electrons transported to O2. In addition, because of the negative sign of the free energy available in the electron transfer, this process is exergonic.

7. Mitochondrial Electron Transport Is a Multicomponent System The final steps in the overall oxidation of foodstuffs— carbohydrates, fats, and amino acids – results in formation of NAD and FADH2 in the matrix. The electron transport chain oxidizes these reduced cofactors by transferring electrons in a series of steps to O2, the terminal electron acceptor, while capturing the free energy of the oxidation-reductions to drive the synthesis of ATP. During removal of electrons from the coenzymes, protons are also removed and pumped from the matrix across the inner membrane to form an electrochemical gradient, which provides energy for synthesis of ATP. The various electron carriers involved in transfer of electrons from NADH to O2 have standard redox potentials that span the range from that of the most electronegative electron donor NADH, with a standard redox potential of -0.32 V, to the most electropositive electron acceptor O2 with a standard redox potential of +0.82 V. electrons are removed from reactants with more negative reduction potentials and transferred to electron acceptors with more positive reduction potentials.

8. The mitochondrial electron carriers : Are grouped into four large multisubunit enzyme complexes: (complexes I-IV) that catalyze different partial reactions of the electron transport chain. The four complexes of the electron transport chain include: 1-Complex I: NADH-ubiquinone oxidoreductase, that catalyzes the transfer of electrons from NADH to ubiquinone (UQ) or also referred to as coenzyme Q (CoQ); 2-Complex II: succinate –ubiquinone oxidoreductase or succinate dehydrogenase, that transfers electrons from succinate to coenzyme Q; 3- Complex III: the cytochrome bc1 complex, ubiquinol- cytochrome c reductase, that transfers electrons from ubiquinol (reduced form of ubiquinone abbreviated as CoQH2 or UQH2) to cytochrome c; 4- Complex IV: cytochrome c oxidase, that transfers electrons from cytochrome c to O2. Another multiprotein complex, the ATP synthase, also called complex V, uses energy of the electrochemical gradient produced during electron transfer for synthesis of ATP.