Cellular respiration is the process by which cells extract energy from organic molecules (primarily glucose) and convert it to ATP. Aerobic respiration proceeds in four stages: glycolysis (cytoplasm), pyruvate oxidation (mitochondrial matrix), the Krebs cycle (mitochondrial matrix), and the electron transport chain/oxidative phosphorylation (inner mitochondrial membrane). The complete oxidation of one glucose molecule yields a theoretical maximum of ~30–32 ATP. Oxygen is the final electron acceptor in aerobic respiration, producing water as a byproduct.
Build an accounting table of ATP, NADH, and FADH₂ produced at each stage. Understand that most ATP comes not from substrate-level phosphorylation but from the electron transport chain using the electron carriers made in earlier stages.
Cellular respiration is the answer to a fundamental question: how does a cell turn a glucose molecule into the ATP it needs to do work? The answer involves four sequential stages that strip glucose of its electrons, use those electrons to pump protons, and then harvest the proton gradient as ATP.
Glycolysis happens in the cytoplasm and does not require oxygen. One glucose (6 carbons) is split into two pyruvate molecules (3 carbons each), yielding 2 ATP and 2 NADH. This is an ancient, universal pathway — every living organism uses it. The ATP yield is small, but the NADH produced is crucial for what follows.
The remaining three stages occur in or on the mitochondria. Pyruvate oxidation converts each pyruvate to acetyl-CoA (2 carbons), releasing CO₂ and producing NADH. The Krebs cycle (in the mitochondrial matrix) takes each acetyl-CoA through a series of reactions that release the remaining carbons as CO₂ while generating more NADH and FADH₂, plus a small amount of ATP directly. By the end of the Krebs cycle, glucose has been completely oxidized — every carbon has been released as CO₂ — but most of the energy is still trapped in the electron carriers NADH and FADH₂.
The electron transport chain (ETC), embedded in the inner mitochondrial membrane, is where the payoff happens. NADH and FADH₂ donate their electrons to protein complexes in the membrane. As electrons pass from one complex to the next, energy is released and used to pump H⁺ ions (protons) from the matrix to the intermembrane space, building an electrochemical gradient. ATP synthase acts like a turbine: protons flowing back through it power the synthesis of ATP from ADP + Pᵢ. This process — oxidative phosphorylation — generates roughly 26–28 of the total ~30–32 ATP per glucose. Oxygen is the final electron acceptor, combining with electrons and protons to form water. Without oxygen, the ETC stalls, NAD⁺ and FAD cannot be regenerated, and the entire pathway backs up.
One important correction to older textbooks: the commonly cited figure of 36–38 ATP is an overestimate. Current measurements, accounting for membrane leakage and the energy cost of transporting ATP out of the mitochondria, put the realistic yield closer to 30–32 ATP per glucose.