Regulation of Oxidative Phosphorylation

• ATP yield from complete oxidation of glucose

  • Glycolysis
  • 2 cytosolic NADH then yields 3 or 5 ATP
  • 2 ATP
  • Pyruvate oxidation, two per glucose
  • 2 mitochondrial matrix NADH then yield 5 ATP
  • Acetyl CoA oxidation if the citric acid cycle, two per glucose
  • 6 mitochondrial matrix NADH then yield 15 ATP
  • 2 FADH2 then yield 3 ATP
  • 2 ATP or 2 GTP
  • Total yield per glucose: 30 or 32 ATP
• Glycolysis under anaerobic conditions yields only 2 ATP per glucose
• Oxidative phosphorylation is regulated by cellular energy needs.
• The acceptor control of respiration is ADP

  • The rate of oxygen consumption depends on the availability of ADP, the Pi acceptor
• The acceptor control ratio of the maximal rate of ADP induced oxygen consumption to the basal rate in the absence of ADP

  • At least 10 in some animal tissues
• The mass action ration is [ATP]/ ([ADP][Pi])

  • Usually this ratio is very high
  • When lowered (and more ADP is available) the rate of respiration increases.
• Which molecule is part of an important mass action ratio in most cells is a modulator of the three major ATP producing pathways?

  • ADP
  • NAD+
  • AMP
  • Acetate
  • NADH


  ADP. The mass action ration of the ATP-ADP system is [ATP]/([ADP][Pi]). With more ADP available for oxidative phosphorylation, the rate of respiration increases, causing regeneration of ATP. This continues until the mass action ratio returns to its normal high level, at which point respiration slows again.
• IF1 is a protein inhibitor that simultaneously binds 2 ATP molecules to inhibit enzyme activity in both directions.

  • Active in its dimeric form, which occurs when pH < 6.5
• In hypoxic (oxygen deprived) cells, IF1 binds and prevents a drastic drop in ATP concentration.
• Hypoxia leads to ROS production and several adaptive responses.
• Defenses against ROS:

  • Glutathione peroxidase system
  • Regulation of pyruvate dehydrogenase
  • Phosphorylated (inactive) under hypoxic conditions
  • Modification of a subunit of Complex IV (COX4-1 to COX4-2)
  • Acts more efficiently under hypoxic conditions
• ATP and ADP relative concentrations control the rates of:

  • Electron transfer
  • Oxidative phosphorylation
  • The citric acid cycle
  • Pyruvate oxidation
  • Glycolysis
• Glycolysis

  • Hexokinase is inhibited by glucose 6-phosphate and stimulated by Pi
  • Phosphofructokinase-1 is inhibited by ATP and citrate and stimulated by AMP and ADP
  • Pyruvate kinase is inhibited by ATP and NADH and stimulated by ADP
• Pyruvate dehydrogenase complex is inhibited by acetyl CoA, ATP, and NADH and is stimulated by AMP, ADP, and NAD+
• Citric Acid cycle:

  • Citrate synthase is inhibited by citrate, ATP, and NADH and stimulated by ADP
  • Isocitrate dehydrogenase is inhibited by ATP and stimulated by ADP
  • Alpha-ketoglutarate dehydrogenase is inhibited by succinyl CoA, ATP, and NADH
• Oxidative phosphorylation is stimulated by ADP and Pi
• How is oxidative phosphorylation inhibited during anaerobic conditions?

  • A lack of terminal electron acceptor blocks the electron transfer chain
  • ADP levels decrease
  • A buildup of glycolytic products (pyruvic acid, lactic acid) lowers pH
  • Inhibitory protein IF1 becomes functionally dimeric under acidic conditions and binds ATP synthase, inhibiting it
  • All of the answers are correct

  All of the answers are correct
• Under anaerobic conditions, the main source of ATP becomes glycolysis, and the pyruvic or lactic acid formed lowers the pH in the cytosol and the mitochondrial matrix. This favors IF1, dimerization, leading to inhibition of ATP synthase. The rate of oxidative phosphorylation also decreases when less ADP (the substrate) and oxygen (the terminal electron acceptor) are available.