Figure: electron transport

Expression

• tissues with high rates of oxidative phosphorylation include:
  • muscle, heart, & brain

Pathology

• the overall process is hugely inefficient
• the free energy for the formation of ATP from ADP is only +7.3 kcal/mole
• the 52.6 kcal/mole used from electron transfer to accomplish this leads to an efficiency of about 14%

• inefficient transfer of electrons leads to potential hazzards, especially with transfer of electrons to O2
• partial reduction products of O2, peroxides, hydroxyl radical & superoxide are cytotoxic & mutagenic
• thus mechanisms have evolved to scavenge these reactive oxygen species produced during oxidative phosphorylation
• considerable debate regarding the biological significance these reactive oxygen species surrounds the 'Free Radical Theory of Aging' proposed by Denham Harman in 1956.

Biochemistry

• reduction of molecular oxygen at the inner mitochondrial membrane with production of ATP
• H+ gradient (higher pH with the mitochondrial matrix) provides driving force for F1 ATPase.

• oxidative phosphorylation or electron transport in eukaryotes occurs in mitochondria
• it takes place in the inner mitochondrial membrane, in contrast to the reactions of the citric acid cycle & fatty acid oxidation which occur in the mitochondrial matrix

• in oxidative phosphorylation, the electron transfer potential of NADH or FADH2 is converted into the phosphate-transfer potential of ATP
• the driving force of oxidative phosphorylation is the electron transfer potention of NADH or FADH2 relative to molecular oxygen (O2). For NADH this is:

1/2 O2 + 2 H+ + 2 e-      ->    H2O                 Eo = +0.82 V
                NADH      ->    NAD+  + H+  + 2e-   Eo = +0.32 V
----------------------------------------------------------------
1/2 O2  +  NADH  +  H+    ->     H2O  + NAD+         E = +1.14 V

• the free energy is thus given by: G = nfE = (-2) (23.06) (1.14) = - 52.6 kcal/mole

• electrons are transferred from NADH to O2 through a chain of 3 macromolecular complexes: complex I (NADH dehydrogenase), complex III (CoQ-cytochrome C reductase) & complex IV (cytochrome C oxidase)
• electron flow within these complexes leads to pumping of protons from the mitochondrial matrix across the inner mitochondrial membrane into the intermembrane space.
• electrons are transferred from FADH2 to O2 through complex II (succinate dehydrogenase), complex III & complex IV
• electrons are shuttled between the complexes (complex I & complex II) & (complex II & complex III) by reduced coenzyme Q (CoQH2)
• cytochrome C shuttles electrons from complex III to complex IV

• complex IV catalyzes transfer of electrons from reduced cytochrome C to O2, the final electron acceptor
• 4 electrons are transferred to O2 to completely reduce it to H2O with concomitant transfer of H+ from the mitochondrial matrix across the inner mitochondrial membrane into the intermembrane space

• complex V utilizes the proton-motive force generated by movement of protons across the inner mitochondrial membrane during electron transport to phosphorylate ATP