Biology · Introductory biology · Concept

Cellular respiration: from glucose to ATP

Cellular respiration releases the energy stored in glucose a little at a time and captures it as ATP. Glycolysis splits glucose into two pyruvate in the cytosol. In the mitochondrion each pyruvate becomes acetyl-CoA, and the citric acid cycle oxidizes the acetyl group to CO₂. These stages make only 4 ATP per glucose directly; most of the energy leaves them as electrons carried by NADH and FADH₂, which the electron transport chain passes to oxygen while it builds the proton gradient that drives ATP synthase.

The overall reaction

Respiration oxidizes glucose completely to carbon dioxide and reduces oxygen to water. Burning glucose releases the same energy all at once as heat; respiration releases it in small steps, and a cell captures about a third of it as ATP.

C_{6} H_{12} O_{6} + 6 O_{2} \to 6 {CO}_{2} + 6 H_{2} O

\begin{array}{c} C_{6} H_{12} O_{6} + 6 O_{2} \\ \to 6 {CO}_{2} + 6 H_{2} O \end{array}

Glycolysis: glucose to pyruvate

In the cytosol, glycolysis splits one glucose, with six carbons, into two pyruvate of three carbons each. It spends 2 ATP and makes 4, a net gain of 2, and reduces 2 NAD⁺ to NADH. It needs no oxygen, and nearly all organisms use it.

Pyruvate oxidation and the citric acid cycle

Each pyruvate enters the mitochondrial matrix and loses one carbon as CO₂, becoming acetyl-CoA and making one NADH. The citric acid cycle, also called the Krebs cycle, joins each two-carbon acetyl group to oxaloacetate, with four carbons, to make citrate, with six. Two oxidations that each release CO₂ bring it back to four carbons, and the rest of the cycle regenerates oxaloacetate. One turn makes 3 NADH, 1 FADH₂ and 1 ATP or GTP; a glucose supplies two acetyl groups, so the cycle turns twice.

One turn of the citric acid cycle

Step	Reaction	Carbons	Made
1	Acetyl-CoA + oxaloacetate → citrate	2 + 4 → 6	—
2	Citrate → isocitrate	6	—
3	Isocitrate → α-ketoglutarate	6 → 5	NADH, CO₂
4	α-ketoglutarate → succinyl-CoA	5 → 4	NADH, CO₂
5	Succinyl-CoA → succinate	4	ATP or GTP
6	Succinate → fumarate	4	FADH₂
7	Fumarate → malate	4	—
8	Malate → oxaloacetate	4	NADH

Oxidative phosphorylation

NADH and FADH₂ hand their electrons to the electron transport chain in the inner mitochondrial membrane. As the electrons pass along the chain to oxygen, the final acceptor, which becomes water, the chain pumps protons into the intermembrane space. The protons flow back through ATP synthase, which uses their flow to make ATP; this coupling is called chemiosmosis. Common estimates are about 2.5 ATP per NADH and 1.5 per FADH₂, so this stage makes most of the ATP.

Without oxygen: fermentation

With no oxygen to accept electrons, the chain stops and NADH can no longer be reoxidized there. Fermentation regenerates NAD⁺ instead by passing NADH’s electrons to pyruvate or a product made from it: muscle makes lactate, and yeast makes ethanol and CO₂. Glycolysis can then keep going, but a glucose yields only its 2 ATP.

Common mistakes

Saying the citric acid cycle makes most of the ATP: it makes 2 per glucose directly; most comes from oxidative phosphorylation.
Counting one turn of the cycle per glucose: each glucose gives two acetyl-CoA, so the cycle turns twice.
Forgetting the CO₂ released when pyruvate becomes acetyl-CoA: glucose’s six carbons leave as six CO₂, two there and four in the cycle.
Thinking the citric acid cycle uses oxygen: oxygen is used only at the end of the electron transport chain, though the cycle stops without it because NAD⁺ and FAD are not regenerated.

Key terms

Cellular respiration: A set of reactions extracting usable energy from fuel molecules. Aerobic respiration uses oxygen as the terminal electron acceptor in its respiratory chain.
Glycolysis: A pathway converting glucose into pyruvate while producing ATP and reduced electron carrier. Glycolysis itself does not directly require molecular oxygen.
Citric acid cycle: A cyclic pathway oxidizing acetyl-derived carbon and regenerating its starting acceptor. It supplies reduced electron carriers and intermediates for other metabolism.
Acetyl group: A two-carbon chemical group transferred in metabolism, often carried by coenzyme A. Entry into the citric acid cycle does not mean every carbon exits immediately.
Reduced electron carrier: A molecule carrying reducing equivalents between reactions. Different carriers serve different metabolic roles; their presence does not identify a complete pathway by itself.
Electron transport chain: A series of proteins and carriers in a membrane that pass electrons along, pumping protons across the membrane as they go. In respiration it takes electrons from NADH and FADH₂ and hands them to oxygen; in a chloroplast it carries them from water to NADP⁺.
Oxidative phosphorylation: ATP synthesis powered by the electron transport chain: protons pumped across the inner mitochondrial membrane flow back through ATP synthase, which uses their flow to make ATP, a coupling called chemiosmosis. It makes most of the ATP from glucose.
Fermentation: A way to keep glycolysis running without oxygen: NADH passes its electrons to pyruvate or a product made from it, regenerating NAD⁺. Muscle cells make lactate; yeast makes ethanol and CO₂. Only glycolysis’s 2 ATP per glucose are made.
Adenosine triphosphate: A nucleotide used in cellular energy coupling. Its hydrolysis can drive an otherwise unfavorable process when reactions are coupled under suitable conditions.
Mitochondrion: An organelle central to aerobic energy metabolism in many eukaryotes. It supports oxidative phosphorylation and also performs other cellular functions.

Work through an example

Follow one glucose molecule through glycolysis, pyruvate oxidation and the citric acid cycle. How many ATP, NADH, FADH₂ and CO₂ does it make? About how many ATP does it give in all once NADH and FADH₂ pass their electrons to the electron transport chain? Use 2.5 ATP per NADH and 1.5 per FADH₂.

Count the ATP made from one glucose →

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