Cellular Respiration: The Chemistry of Burning Glucose

Hold a lit match to a sugar cube (with a pinch of ash as a catalyst) and it burns with a blue flame, releasing its energy as heat and light in seconds. Your cells “burn” the same sugar, glucose, with the same oxygen, making the same products, carbon dioxide and water. But they do it at 37 °C, without flames, and they capture a large part of the energy in a useful form. Cellular respiration is combustion tamed: a long chain of small, enzyme-controlled redox reactions.

The overall reaction

Aerobic respiration of glucose has the same overall equation as burning it:

C₆H₁₂O₆ + 6O₂ → 6CO₂ + 6H₂O

The free energy released is about ΔG ≈ −2,870 kJ mol⁻¹ of glucose. (The enthalpy of combustion is similar, about −2,800 kJ mol⁻¹.) This is a strongly exothermic, spontaneous reaction (see exothermic vs endothermic).

Chemically, it’s a redox reaction (see oxidation and reduction):

• glucose is oxidised to carbon dioxide: its carbon atoms lose electrons (the average oxidation state of carbon rises from 0 in glucose to +4 in CO₂);
• oxygen is reduced to water: its oxidation state falls from 0 to −2.

Why not just burn it?

If a cell released 2,870 kJ mol⁻¹ in one step, almost all of it would be lost as heat, and the cell would cook. Instead, respiration:

• breaks glucose down in many small steps, each catalysed by its own enzyme;
• removes electrons from glucose gradually, handing them to carrier molecules;
• releases energy in small packets that can be captured by making ATP (see ATP: the cell’s energy currency).

The trick is that glucose never meets oxygen directly. Electrons stripped from glucose are carried away by the coenzymes NAD⁺ and FAD, which become NADH and FADH₂. Only at the very end are these electrons passed to oxygen, down a series of proteins that capture their energy step by step.

The four stages

Stage 1: Glycolysis (in the cytoplasm)

• Glucose (6 carbons) is split into two pyruvate molecules (3 carbons each).
• Net gain: 2 ATP and 2 NADH per glucose.
• Needs no oxygen, so it’s the same in aerobic and anaerobic respiration.

Full details: glycolysis step by step.

Stage 2: The link reaction (in the mitochondrial matrix)

Each pyruvate enters a mitochondrion and is converted to acetyl-CoA:

pyruvate + CoA + NAD⁺ → acetyl-CoA + CO₂ + NADH

• One carbon leaves as CO₂, the first carbon dioxide produced.
• Per glucose (two pyruvates): 2 CO₂ and 2 NADH.
• The enzyme complex responsible, pyruvate dehydrogenase, needs several coenzymes made from B vitamins, including thiamine (see cofactors and coenzymes).

Stage 3: The Krebs cycle (in the mitochondrial matrix)

Each acetyl group (2 carbons) joins a 4-carbon molecule and is oxidised completely to 2 CO₂ as the cycle turns. Per glucose (two turns):

• 4 CO₂
• 6 NADH
• 2 FADH₂
• 2 ATP (as GTP or ATP)

By the end of this stage, all six carbon atoms of glucose have left as CO₂. Details: the Krebs cycle.

Stage 4: Oxidative phosphorylation (on the inner mitochondrial membrane)

This is where most of the ATP is made and where oxygen finally appears:

1. NADH and FADH₂ hand their electrons to the electron transport chain, a series of protein complexes in the inner membrane.
2. As electrons pass along the chain towards oxygen, their energy is used to pump protons (H⁺) out of the matrix, building up a concentration and charge difference across the membrane.
3. Protons flow back through ATP synthase, which uses their energy to make ATP from ADP and phosphate.
4. At the end, electrons combine with oxygen and protons to form water: O₂ + 4H⁺ + 4e⁻ → 2H₂O.

Details: the electron transport chain.

Summary table (per glucose)

Stage	Location	CO₂	NADH	FADH₂	ATP made directly
Glycolysis	Cytoplasm	0	2	0	2 (net)
Link reaction	Matrix	2	2	0	0
Krebs cycle	Matrix	4	6	2	2
Oxidative phosphorylation	Inner membrane	0	(used)	(used)	~26–28
Total		6	10	2	~30–32

The number from oxidative phosphorylation depends on how many protons are needed per ATP and how NADH from glycolysis gets into the mitochondrion. Modern estimates are about 2.5 ATP per NADH and 1.5 ATP per FADH₂, giving roughly 30 to 32 ATP per glucose. (Older textbooks often quote 36 or 38, based on earlier estimates.)

How efficient is respiration?

Under standard conditions, making one ATP stores about 30.5 kJ mol⁻¹. For 32 ATP:

32 × 30.5 ≈ 976 kJ captured out of 2,870 kJ released → about 34% efficient.

Using the larger free energy of ATP hydrolysis under real cell conditions (around 50 kJ mol⁻¹), the efficiency comes out higher, perhaps 50% or more. Either way, it compares well with a typical car engine (roughly 25 to 30%). The rest of the energy is released as heat, which is how mammals and birds keep warm.

Where the oxygen goes and where the carbon goes

A common exam trap: the oxygen atoms you breathe in end up in water, not in carbon dioxide. The oxygen atoms in the CO₂ you breathe out come from glucose and from water molecules used in the Krebs cycle. This was confirmed using oxygen-18 isotope labelling.

Other fuels

Glucose isn’t the only fuel. Cells feed other molecules into the same pathway:

• Fats: fatty acids are chopped into two-carbon acetyl-CoA units (β-oxidation), which enter the Krebs cycle. Fats yield much more ATP per gram because they’re more reduced.
• Proteins: amino acids lose their amino groups (which become urea) and their carbon skeletons enter glycolysis or the Krebs cycle at various points.

This is why the Krebs cycle is often called the hub of metabolism.

When there’s no oxygen

Without oxygen, the electron transport chain stops, NADH piles up and NAD⁺ runs out, so the Krebs cycle and link reaction halt. Cells can still make a little ATP from glycolysis if they regenerate NAD⁺ another way, by turning pyruvate into lactate (in animals) or ethanol and CO₂ (in yeast). See aerobic vs anaerobic respiration.

Common misconceptions

• “Respiration means breathing.” Breathing (ventilation) supplies oxygen and removes CO₂; respiration is the chemical process inside cells.
• “Respiration makes energy.” Energy can’t be created; respiration releases energy from glucose and captures some of it in ATP.
• “Only animals respire.” Plants respire all the time too, as do fungi and most bacteria.
• “The oxygen we breathe is turned into CO₂.” It’s turned into water.

Key takeaways

• Aerobic respiration: C₆H₁₂O₆ + 6O₂ → 6CO₂ + 6H₂O, ΔG ≈ −2,870 kJ mol⁻¹; it’s a controlled redox reaction.
• Energy is released in small steps, with electrons carried by NAD⁺ and FAD.
• Four stages: glycolysis (cytoplasm), link reaction and Krebs cycle (matrix), oxidative phosphorylation (inner membrane).
• Yield: about 30–32 ATP per glucose, roughly 34% efficient under standard conditions.
• Oxygen is the final electron acceptor and becomes water. For how plants make the glucose in the first place, see what is biochemistry?.