Leakage of electrons from the ETC produces reactive oxygen species (ROS), such as superoxide (O2−·), hydrogen peroxide (H2O2), and hydroxyl radicals (OH·). ROS damage DNA and proteins and cause lipid peroxidation. Enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase are cellular defenses against ROS (see p. 148).
D. Free energy release during electron transport
The free energy released as electrons are transferred along the ETC from an electron donor (reducing agent or reductant) to an electron acceptor (oxidizing agent or oxidant) is used to pump H+ at Complexes I, III, and IV. [Note: The electrons can be transferred as hydride ions to NAD+; as hydrogen atoms to FMN, CoQ, and FAD; or as electrons to cytochromes.] 1.
Redox pairs: Oxidation (loss of electrons) of one substance is always accompanied by reduction (gain of electrons) of a second. For example, Figure 6.11 shows the oxidation of NADH to NAD+ by NADH dehydrogenase at Complex I, accompanied by the reduction of FMN, the prosthetic group, to FMNH2. Such redox reactions can be written as the sum of two separate half reactions, one an oxidation and the other a reduction (see Fig. 6.11). NAD+ and NADH form a redox pair, as do FMN and FMNH2. Redox pairs differ in their tendency to lose electrons. This tendency is a characteristic of a particular redox pair and can be quantitatively specified by a constant, E0 (the standard reduction potential), with units in volts.
2.
Standard reduction potential: The E0 of various redox pairs can be ordered from the most negative E0 to the most positive. The more negative the E0 of a redox pair, the greater the tendency of the reductant member of that pair to lose electrons. The more positive the E0, the greater the tendency of the oxidant member of that pair to accept electrons. Therefore, electrons flow from the pair with the more negative
E0 to that with the more positive E0. The E0 values for some members of the ETC are shown in Figure 6.12. [Note: The components of the chain are arranged in order of increasingly positive E0 values.] 3. Relationship of ∆G0 to ∆E0: The ∆G0 is related directly to the magnitude of the change in E0: where n = number of electrons transferred (1 for a cytochrome, 2 for NADH, FADH2, and CoQ)
F = Faraday constant (23.1 kcal/volt mol) ∆E0 = E0 of the electron-accepting pair minus the E0 of the electron-donating pair ∆G0 = change in the standard free energy 4. ∆G0 of ATP: The ∆G0 for the phosphorylation of ADP to ATP is +7.3 kcal/mol. The transport of a pair of electrons from NADH to O2 through the ETC releases 52.6 kcal. Therefore, more than sufficient energy is available to produce three ATP from three ADP and three Pi (3 × 7.3 = 21.9 kcal/mol), sometimes expressed as a P/O ratio (ATP made per O atom reduced) of 3:1. The remaining calories are used for ancillary reactions or released as heat. [Note: The P:O for FADH2 is 2:1 because
Complex I is bypassed.]
VI. PHOSPHORYLATION OF ADP TO ATP
The transfer of electrons down the ETC is energetically favored because NADH is a strong electron donor and O2 is an avid electron acceptor. However, the flow of electrons does not directly result in ATP synthesis.
A. Chemiosmotic hypothesis
The chemiosmotic hypothesis (also known as the Mitchell hypothesis) explains how the free energy generated by the transport of electrons by the ETC is used to produce ATP from ADP + Pi.
1.