In cellular respiration in eukaryotic cells, which stage of the pathway (from glycolysis through the Krebs cycle to oxidative phosphorylation) produces the greatest amount of ATP per molecule of glucose?

Introduction / Context:
Cellular respiration is the process by which cells harvest energy from glucose and store it in the form of ATP (adenosine triphosphate). It occurs in several stages: glycolysis, the link reaction, the Krebs cycle, and the electron transport chain with oxidative phosphorylation. Many students remember the names of these stages but are not always clear about which stage produces the bulk of the ATP. This question tests your understanding of the relative ATP yield of each stage of cellular respiration.

Given Data / Assumptions:

• Aerobic respiration of one molecule of glucose is considered.
• The standard pathway includes glycolysis, the Krebs cycle, and the electron transport chain with oxidative phosphorylation.
• ATP production at each stage is being compared.
• We assume oxygen is available and the electron transport chain is functioning normally.

Concept / Approach:
Glycolysis occurs in the cytoplasm and yields a small net gain of ATP directly by substrate level phosphorylation. The Krebs cycle, located in the mitochondrial matrix, also produces a small amount of ATP directly but generates high energy electron carriers NADH and FADH2. The majority of ATP comes later, when these carriers donate electrons to the electron transport chain in the inner mitochondrial membrane. As electrons pass through a series of carriers, energy is released and used to pump protons, which then flow back through ATP synthase, driving oxidative phosphorylation. Therefore, the stage that produces the most ATP is the electron transport chain coupled to oxidative phosphorylation.

Step-by-Step Solution:
Step 1: Recall that glycolysis yields a net of about 2 ATP directly per glucose molecule. Step 2: Remember that the Krebs cycle produces only 1 ATP (or GTP) per turn, which is 2 ATP per glucose, but generates many NADH and FADH2 molecules. Step 3: Note that each NADH and FADH2 can drive the synthesis of multiple ATP molecules when their electrons enter the electron transport chain. Step 4: Understand that the electron transport chain uses these electrons to create a proton gradient that powers ATP synthase during oxidative phosphorylation. Step 5: Compare the direct ATP from glycolysis and the Krebs cycle with the much larger ATP yield from oxidative phosphorylation, and conclude that the electron transport chain stage produces the most ATP.

Verification / Alternative check:
In most textbook calculations, complete aerobic oxidation of one molecule of glucose yields about 30 to 32 ATP. Of this total, glycolysis contributes only a small fraction directly, and the Krebs cycle contributes a small fraction directly. The remainder, usually more than 80 percent of the ATP, comes from oxidative phosphorylation driven by the electron transport chain. This quantitative comparison confirms that the electron transport chain and oxidative phosphorylation stage is the major ATP producing step of cellular respiration.

Why Other Options Are Wrong:
Glycolysis in the cytoplasm: This stage produces only a small net gain of ATP (about 2 ATP per glucose) and is not the main ATP source. Krebs cycle (citric acid cycle) in the mitochondrial matrix: This cycle produces a little ATP directly but mainly generates NADH and FADH2 for later stages. Link reaction (pyruvate oxidation) between glycolysis and the Krebs cycle: This step produces NADH but does not directly generate large amounts of ATP. All stages produce approximately the same amount of ATP: This is incorrect because the electron transport chain produces far more ATP than the earlier stages.

Common Pitfalls:
A common mistake is to assume that the Krebs cycle must produce the most ATP because it is called the central metabolic hub. While it is central for generating reduced coenzymes, the majority of ATP is actually produced later through oxidative phosphorylation. Another pitfall is forgetting the distinction between substrate level phosphorylation (direct ATP formation in glycolysis and the Krebs cycle) and oxidative phosphorylation (ATP formed using a proton gradient in the electron transport chain). Keeping this distinction clear makes it easier to remember which stage yields the most ATP.

Final Answer:
The stage of cellular respiration that produces the greatest amount of ATP is the Electron transport chain and oxidative phosphorylation in the inner mitochondrial membrane.