Cellular Respiration Phases

Why This Matters

Cellular respiration is the metabolic backbone of nearly every living organism—it's how your cells extract usable energy from the food you eat. On the AP exam, you're being tested on more than just memorizing steps; you need to understand energy transformation, electron flow, and the role of compartmentalization in making this process efficient. Questions often ask you to trace carbon atoms through the pathway, explain why oxygen is essential, or compare energy yields across stages.

Think of cellular respiration as a story of energy currency conversion: glucose holds chemical energy in its bonds, and through a series of carefully orchestrated reactions, cells convert that energy into ATP—the molecule that actually powers cellular work. Each phase has a specific location, specific inputs and outputs, and a specific role in the bigger picture. Don't just memorize the phases—know what each phase accomplishes and why it happens where it does.

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Substrate-Level Reactions: Direct ATP Production

These phases generate ATP directly through enzyme-catalyzed reactions, without requiring the electron transport chain. The phosphate group is transferred directly from a substrate molecule to ADP.

Glycolysis

• Occurs in the cytoplasm and is completely anaerobic—this is the universal first step shared by all respiration pathways, including fermentation
• Splits one glucose ($C_6H_{12}O_6$) into two pyruvate molecules—net yield of 2 ATP and 2 NADH after the energy investment phase
• Two phases within glycolysis: the energy investment phase uses 2 ATP, while the energy payoff phase generates 4 ATP and 2 NADH

Citric Acid Cycle (Krebs Cycle)

• Located in the mitochondrial matrix—requires acetyl-CoA from pyruvate oxidation to combine with oxaloacetate and begin the cycle
• Completes glucose oxidation by releasing the remaining carbons as $CO_2$—produces 3 NADH, 1 $FADH_2$, and 1 ATP (or GTP) per turn
• Runs twice per glucose molecule—since each glucose yields two acetyl-CoA, total cycle output doubles for complete glucose breakdown

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Preparatory Reactions: Setting Up for Energy Extraction

This transitional phase doesn't produce ATP directly but is essential for connecting glycolysis to the citric acid cycle. It converts pyruvate into a form that can enter the cycle.

Pyruvate Oxidation

• Occurs in the mitochondrial matrix—pyruvate crosses both mitochondrial membranes to reach this location
• Converts each pyruvate to acetyl-CoA—releases one $CO_2$ and generates one NADH per pyruvate molecule
• Links glycolysis to the Krebs cycle—happens twice per glucose since glycolysis produces two pyruvate molecules

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Oxidative Reactions: Harvesting Energy from Electrons

These final phases extract the majority of ATP by using electron carriers (NADH and $FADH_2$) built up in earlier stages. The energy stored in electrons is used to establish a proton gradient, which then drives ATP synthesis.

Electron Transport Chain

• Embedded in the inner mitochondrial membrane—consists of protein complexes (I, II, III, IV) and mobile carriers that pass electrons in sequence
• Pumps protons ($H^+$) into the intermembrane space—electron energy is used to establish a proton gradient (also called the proton-motive force)
• Oxygen is the final electron acceptor—combines with electrons and $H^+$ to form water; without $O_2$, the chain stops and ATP production crashes

Oxidative Phosphorylation

• Driven by the proton gradient—$H^+$ ions flow back through ATP synthase, and this flow powers the enzyme to synthesize ATP from ADP + $P_i$
• Produces approximately 26-28 ATP per glucose—this is the vast majority of cellular respiration's total ATP yield
• Chemiosmosis is the mechanism—the coupling of electron transport to ATP synthesis via a proton gradient; this concept appears frequently on exams

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Quick Reference Table

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Self-Check Questions

1. Which two phases produce ATP through substrate-level phosphorylation, and how does this differ from oxidative phosphorylation?

2. Trace a single carbon atom from glucose through cellular respiration—at which phase(s) is it released as $CO_2$?

3. Compare the roles of NADH in glycolysis versus in the electron transport chain. Why is NADH considered an "electron carrier"?

4. If a cell is exposed to cyanide (which blocks Complex IV of the ETC), what happens to ATP production and why does the citric acid cycle also stop?

5. Explain why glycolysis can continue during anaerobic conditions while the citric acid cycle cannot. What must happen to pyruvate instead?