The citric acid cycle is a crucial metabolic process that breaks down nutrients to generate energy. It's the central hub where carbs, fats, and proteins converge, producing molecules that power our cells. This cycle is like a cellular recycling plant, constantly churning out energy-rich compounds.

The electron transport chain and oxidative phosphorylation are the grand finale of cellular respiration. They use the products from the citric acid cycle to create a massive energy surge, pumping out ATP like a power plant. It's here that our cells truly maximize their energy production.

Citric Acid Cycle

Steps of citric acid cycle

1. Acetyl-CoA combines with oxaloacetate to form citrate, catalyzed by citrate synthase
2. Citrate is converted to isocitrate by aconitase, which involves a dehydration and rehydration step
3. Isocitrate dehydrogenase oxidizes isocitrate to α-ketoglutarate, reducing NAD+ to NADH and releasing CO2
4. α-Ketoglutarate dehydrogenase complex converts α-ketoglutarate to succinyl-CoA, reducing NAD+ to NADH and releasing CO2
5. Succinyl-CoA synthetase catalyzes the conversion of succinyl-CoA to succinate, generating GTP (or ATP) via substrate-level phosphorylation
6. Succinate dehydrogenase (Complex II) oxidizes succinate to fumarate, reducing FAD to FADH2
7. Fumarase catalyzes the hydration of fumarate to malate
8. Malate dehydrogenase oxidizes malate to oxaloacetate, reducing NAD+ to NADH, completing the cycle

• The citric acid cycle is a central metabolic hub that oxidizes acetyl-CoA derived from carbohydrates (glucose), fats (fatty acids), and proteins (amino acids)
• The NADH and FADH2 generated during the cycle are used in the electron transport chain to produce ATP through oxidative phosphorylation

Electron Transport Chain and Oxidative Phosphorylation

Organization of electron transport chain

• Complex I (NADH dehydrogenase) oxidizes NADH, transferring electrons to ubiquinone (Q) and pumping protons into the intermembrane space
• Complex II (succinate dehydrogenase) oxidizes FADH2, transferring electrons to ubiquinone without pumping protons
• Complex III (cytochrome bc1 complex) transfers electrons from ubiquinol (QH2) to cytochrome c, pumping protons into the intermembrane space
• Complex IV (cytochrome c oxidase) transfers electrons from cytochrome c to oxygen, reducing it to water and pumping protons into the intermembrane space
• Electron transport through the complexes is coupled to the pumping of protons, creating an electrochemical gradient across the inner mitochondrial membrane

Process of oxidative phosphorylation

1. The proton gradient generated by the electron transport chain is used to drive ATP synthesis via ATP synthase (Complex V)
2. Protons flow down their electrochemical gradient through the F0 subunit of ATP synthase, causing the rotation of the F1 subunit
3. The rotation of the F1 subunit catalyzes the synthesis of ATP from ADP and inorganic phosphate (Pi)
4. The proton motive force, consisting of both the pH gradient (ΔpH) and the membrane potential (ΔΨ), drives the flow of protons through ATP synthase
5. ATP is released from the F1 subunit into the mitochondrial matrix and can be transported to other parts of the cell for energy-requiring processes

Concept of chemiosmosis

• Chemiosmosis is the process by which an electrochemical gradient (proton gradient) is used to drive the synthesis of ATP
• The electron transport chain pumps protons from the mitochondrial matrix into the intermembrane space, creating a proton gradient
• The proton gradient represents a form of potential energy called the proton motive force
• ATP synthase harnesses the proton motive force to generate ATP as protons flow back into the matrix through the enzyme complex
• Chemiosmosis couples the redox reactions of the electron transport chain to the phosphorylation of ADP, producing ATP

Energy yield comparisons in respiration

• Aerobic respiration yields the most ATP per glucose molecule (30-32 ATP)
  • Glycolysis: 2 ATP
  • Citric acid cycle: 2 ATP
  • Oxidative phosphorylation: 26-28 ATP
• Anaerobic respiration yields less ATP than aerobic respiration
  • Nitrate respiration (some prokaryotes): 20-25 ATP per glucose
  • Sulfate respiration (some prokaryotes): 15-20 ATP per glucose
• Fermentation yields the least ATP per glucose molecule (2 ATP)
  • Lactic acid fermentation (muscle cells): 2 ATP from glycolysis
  • Ethanol fermentation (yeast): 2 ATP from glycolysis
  • Fermentation relies on substrate-level phosphorylation in glycolysis and does not involve the citric acid cycle or electron transport chain