The process by which cells use oxygen to break down glucose and synthesize large amounts of ATP is cellular respiration (aerobic respiration). Let us understand it at the molecular level by dividing it into three stages.
Basic Knowledge
Stage 1: Glycolysis (cytosol): Glucose (C₆)→2 pyruvate (C₃). 2 ATP molecules are consumed and 4 are produced = net 2 ATP; 2 NADH molecules are produced. Oxygen is not required.
Stage 2: Citric acid cycle/TCA cycle (mitochondrial matrix): Pyruvate→acetyl-CoA (CO₂ released)→condensation with oxaloacetate→citrate→stepwise oxidation. One turn produces 1 ATP molecule (substrate-level phosphorylation), 3 NADH molecules, 1 FADH₂ molecule, and 2 CO₂ molecules. One glucose molecule completes 2 turns = net 2 ATP, 8 NADH molecules, and 2 FADH₂ molecules (including those from glycolysis).
Stage 3: Electron transport chain/oxidative phosphorylation (inner mitochondrial membrane): NADH and FADH₂ transfer electrons to complexes (I–IV) in the inner membrane → H⁺ is pumped into the intermembrane space, forming a concentration gradient → H⁺ passes through ATP synthase (complex V) → large amounts of ATP are synthesized (about 32–34 ATP per glucose). The final electron acceptor is O₂ (reduced to H₂O).
Total ATP yield from one glucose molecule: glycolysis 2 + citric acid cycle 2 + electron transport chain about 28–30 = total about 30–32 ATP.
Explain why the inner membrane of mitochondria is important for ATP synthesis, referring to the relationship between the H⁺ concentration gradient and ATP synthase.
Answer: Complexes in the electron transport chain receive electrons from NADH and FADH₂ and pump H⁺ into the intermembrane space, forming an H⁺ concentration gradient (proton-motive force) across the inner membrane. ATP synthase uses this energy to synthesize ATP from ADP and phosphate. Because the inner membrane is highly impermeable to H⁺, H⁺ can pass through only ATP synthase, allowing this mechanism to work.
- Glycolysis = cytosol, no O₂ required, net 2 ATP, produces 2 NADH
- Citric acid cycle = matrix, CO₂ released, 2 ATP, 8 NADH, 2 FADH₂
- Electron transport chain = inner membrane, O₂ required, about 28–30 ATP
- Final electron acceptor = O₂→H₂O
- Proton-motive force = H⁺ concentration gradient drives ATP synthase rotation
- Total ATP ≈30–32 molecules per glucose
- CO₂ release = during conversion of pyruvate→acetyl-CoA and in the citric acid cycle
Points of Caution
① Glycolysis does not require O₂, but the electron transport chain stops without O₂; NADH cannot be reoxidized, and glycolysis also stops. ② CO₂ is not released during glycolysis; it is released during conversion of pyruvate→acetyl-CoA and in the citric acid cycle. ③ Textbooks give a range of 30–38 for ATP yield, but about 30–32 is currently standard.
Practice
- Give the three stages of cellular respiration together with their locations inside the cell.
- What does O₂ ultimately become in aerobic respiration?
- What is the name of the enzyme that uses the H⁺ concentration gradient in the electron transport chain to synthesize ATP?