1.8

• Oxidative phosphorylation


  ATP is synthesized from ADP as a result of the transfer of electrons and hydrogen ions from NADH or FADH2 to O2 through the electron carriers involved in the electron transport chain
• Oxidative phosphorylation is conceptually simple but mechanistically complex
• Learning the "details" of oxidative phosphorylation has been—and still is—one of the most challenging research areas in biochemistry
• Coupled reactions


  Pairs of biochemical reactions that occur concurrently in which energy released by one reaction is used in the other reaction
• Oxidative phosphorylation and the oxidation reactions of the electron transport chain are coupled systems
• Coupling of ATP synthesis with the reactions of the ETC

  • Related to the movement of protons (H ions) across the inner mitochondrial membrane
  • Three of the four protein complexes involved in the ETC chain (I, III, and IV) have a second function besides electron transfer down the chain - they also serve as "proton pumps", transferring protons from the matrix side of the inner mitochondrial membrane to the intermembrane space
• Some of the H ions crossing the inner mitochondrial membrane come from the reduced electron carriers, and some come from the matrix; the details of how the H ions cross the inner mitochondrial membrane are not fully understood
• For every two electrons passed through the ETC, four protons cross the inner mitochondrial membrane through complex I, four through complex III, and two more through complex IV
• This proton flow causes a buildup of H ions (protons) in the intermembrane space
• Chemiosmotic coupling


  An explanation for the coupling of ATP synthesis with electron transport chain reactions that requires a proton gradient across the inner mitochondrial membrane
• Chemiosmotic coupling


  • The result of the pumping of protons from the mitochondrial matrix across the inner mitochondrial membrane is a higher concentration of protons in the intermembrane space than in the matrix, constituting an electrochemical (proton) gradient
  • A spontaneous flow of protons from the region of high concentration to the region of low concentration occurs because of the electrochemical gradient, through enzyme complexes called ATP synthases located on the inner mitochondrial membrane
  • ATP synthase has two subunits, the F0 and F1 subunits - the F0 part is the channel for proton flow, whereas the formation of ATP takes place in the F1 subunit
• As protons return to the mitochondrial matrix through the F0 subunit, the potential energy associated with the electrochemical gradient is released and used in the F1 subunit for the synthesis of ATP
• Oxidative phosphorylation is not the only process by which ATP is produced in cells - substrate phosphorylation can also produce ATP, but the amount is much less than that produced by oxidative phosphorylation
• The difference in H ion concentration between the two sides of the inner mitochondrial membrane causes a pH difference of about 1.4 units, with the intermembrane space (the more acidic region) having 25 times more protons than the matrix
• Cyanide poisoning inhibits the electron transport chain by inactivating cytochrome c oxidase, the last complex in the chain, preventing the cell's use of oxygen and leading to tissue asphyxiation
• Treatments for cyanide poisoning

  • Administering nitrites to oxidize hemoglobin iron, drawing cyanide back into the bloodstream, and administering thiosulfate to convert cyanide to thiocyanate