Cellular Respiration

The four stages

1 · Glycolysis (cytoplasm)

• Inputs: 1 glucose (6C), 2 ATP, 2 NAD⁺.
• Outputs: 2 pyruvate (3C each), 4 ATP gross / 2 ATP net, 2 NADH.
• Anaerobic-compatible — does not require O₂.
• Investment phase consumes 2 ATP; payoff phase generates 4 ATP via substrate-level phosphorylation.

2 · Pyruvate oxidation (mitochondrial matrix)

• Each pyruvate → 1 acetyl-CoA + 1 CO₂ + 1 NADH.
• Per glucose: 2 acetyl-CoA, 2 CO₂, 2 NADH.
• Requires the pyruvate dehydrogenase complex.

3 · Krebs / citric-acid cycle (mitochondrial matrix)

• Per acetyl-CoA: 3 NADH, 1 FADH₂, 1 ATP (GTP), 2 CO₂.
• Per glucose (×2): 6 NADH, 2 FADH₂, 2 ATP, 4 CO₂.
• All carbons from the original glucose have now left as CO₂.

4 · Oxidative phosphorylation (inner mitochondrial membrane)

• Electron transport chain (ETC): NADH donates electrons to complex I; FADH₂ to complex II; both feed into complex III → IV. As electrons move, energy pumps H⁺ from matrix to intermembrane space.
• Final electron acceptor: O₂ → reduced to H₂O. Without O₂, the chain backs up.
• Chemiosmosis: H⁺ flows back into the matrix through ATP synthase, driving phosphorylation of ADP → ATP.
• Yields: ~2.5 ATP per NADH; ~1.5 ATP per FADH₂.

ATP yield, full picture

Stage	Direct ATP	NADH	FADH₂
Glycolysis	2	2	—
Pyruvate oxidation	0	2	—
Krebs cycle	2	6	2
Subtotal	4	10	2
Oxidative phosphorylation	~25 ATP from 10 NADH (×2.5) + ~3 ATP from 2 FADH₂ (×1.5) = ~28 ATP
Total	~30–32 ATP per glucose

Locations summary

Glycolysis              → Cytoplasm
Pyruvate oxidation      → Mitochondrial matrix
Krebs / citric acid     → Mitochondrial matrix
ETC + ATP synthase      → Inner mitochondrial membrane (cristae)

The ETC, in ASCII

                INTERMEMBRANE SPACE
   ↑ H⁺          ↑ H⁺            ↑ H⁺
┌──┴─┐  ┌─Q─┐ ┌──┴─┐  ┌─cyt c─┐ ┌──┴─┐    ┌──ATP synthase──┐
│ I  │→     →│III │→         →│IV │      │   F₀ → F₁      │
└────┘  └───┘ └────┘  └───────┘ └─O₂─┘    │                │
   ↑                                     ↑↓ H⁺ flow
  NADH        FADH₂ → II                  drives ATP synthesis
                MATRIX

Complex I receives e⁻ from NADH; complex II receives them from FADH₂ (skipping I → fewer H⁺ pumped → lower ATP yield). Q and cytochrome c shuttle electrons between complexes.

Fermentation (anaerobic)

• Purpose: regenerate NAD⁺ so glycolysis can keep producing 2 ATP per glucose.
• Lactic-acid fermentation: pyruvate + NADH → lactate + NAD⁺ (muscle cells, some bacteria).
• Alcoholic fermentation: pyruvate → acetaldehyde + CO₂ → ethanol; NAD⁺ regenerated (yeast).
• Net ATP from fermentation: 2 ATP per glucose (glycolysis only).

Example questions

MCQ If oxygen is unavailable, ATP production is limited because: (A) Glycolysis cannot occur (B) The Krebs cycle continues but ETC stops, halting NAD⁺ regeneration (C) ATP synthase no longer functions (D) Both B and C

Answer: D. Without O₂ as the terminal electron acceptor, the ETC backs up. NADH cannot deposit its electrons → NAD⁺ regeneration in mitochondria stops → Krebs and pyruvate oxidation halt. The proton gradient collapses, so chemiosmosis ceases and ATP synthase has no driving force. Only fermentation-coupled glycolysis continues.

Long FRQ Describe how the structure of the inner mitochondrial membrane supports oxidative phosphorylation, and predict the effect of a drug that creates pores in this membrane on ATP production.

Answer: The inner mitochondrial membrane is folded into cristae, increasing surface area for ETC complexes and ATP synthase. It is impermeable to H⁺, allowing a steep proton gradient to build up in the intermembrane space as the ETC pumps protons. ATP synthase channels H⁺ back to the matrix, using that flow to phosphorylate ADP. A pore-forming drug allows H⁺ to leak through the membrane independent of ATP synthase, dissipating the proton gradient. Without the gradient, chemiosmosis cannot drive ATP synthesis, so ATP production drops dramatically and the energy of NADH/FADH₂ oxidation is dissipated as heat.

MCQ Which produces the LARGEST amount of ATP per glucose? (A) Glycolysis (B) Krebs cycle (C) Oxidative phosphorylation (D) Pyruvate oxidation

Answer: C. Oxidative phosphorylation generates ~28 of the ~30–32 ATP. The other stages produce small amounts via substrate-level phosphorylation, but they primarily supply electron carriers.

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