Glucose is taken apart in stages: split in the cytoplasm, then fed into the mitochondrial matrix two carbons at a time. Carbon leaves as carbon dioxide, and the real prize, hydrogen, is loaded onto NAD and FAD.
Aerobic respiration has four stages: glycolysis in the cytoplasm, the link reaction and Krebs cycle in the mitochondrial matrix, and oxidative phosphorylation on the inner mitochondrial membrane. In glycolysis, glucose is phosphorylated using 2 ATP to fructose 1,6-bisphosphate (6C), which splits into two triose phosphates (3C); these are oxidised to pyruvate (3C), giving a net 2 ATP and 2 reduced NAD. If oxygen is available, pyruvate enters the mitochondrion. In the link reaction it is decarboxylated and dehydrogenated, and the 2C acetyl group is carried by coenzyme A. In the Krebs cycle, oxaloacetate (4C) accepts the acetyl group to form citrate (6C), which is converted back to oxaloacetate in small steps, releasing CO2 and reducing NAD and FAD.
Click each structure of the mitochondrion in turn: outer membrane, inner membrane, cristae, matrix, ATP synthase, ribosomes and circular DNA. Read what each one does and rotate the model to see the folds.
| Stage | Where in a eukaryotic cell |
|---|---|
| glycolysis | cytoplasm |
| link reaction | mitochondrial matrix |
| Krebs cycle | mitochondrial matrix |
| oxidative phosphorylation | inner mitochondrial membrane |
| Structure | How it suits its function |
|---|---|
| outer membrane | contains transport proteins that let pyruvate into the mitochondrion |
| intermembrane space | small volume, so protons pumped into it quickly build a steep gradient |
| inner membrane folded into cristae | large surface area for electron transport chains and ATP synthase; impermeable to protons except through ATP synthase |
| ATP synthase (stalked particles) | on the cristae, facing the matrix; make ATP as protons flow through |
| matrix | contains the enzymes of the link reaction and Krebs cycle, NAD, FAD, circular DNA and 70S ribosomes that make some mitochondrial proteins |
In an electron micrograph a mitochondrion appears as an oval organelle about 1 μm wide, with a double membrane and inner folds (cristae) crossing a granular matrix. Very active cells, such as muscle and sperm tail cells, have many mitochondria with densely packed cristae.
Glycolysis does not happen in the mitochondrion. Glucose never enters it: only pyruvate does, and only when oxygen is available.
Press Next step and follow the carbon atoms of one glucose through the first four steps. Watch the ATP (net) and reduced NAD counters after each step, then keep going through the link reaction and the Krebs cycle.
| Step | What happens | Per glucose |
|---|---|---|
| phosphorylation | two phosphate groups from ATP are added, forming fructose 1,6-bisphosphate (6C); this makes the sugar more reactive and easier to split | 2 ATP used |
| lysis | fructose 1,6-bisphosphate splits into two triose phosphate molecules (3C) | - |
| oxidation | hydrogen is removed from each triose phosphate (dehydrogenation) and reduces NAD; the triose phosphate is converted to pyruvate (3C) | 2 reduced NAD |
| ATP formation | phosphate groups are transferred to ADP: substrate-linked phosphorylation | 4 ATP made, so a net gain of 2 ATP |
Glycolysis makes 4 ATP but uses 2, so the net yield is 2 ATP per glucose. Questions that ask for the net yield expect 2, not 4.
Four quick checks. Each correct answer earns XP and records this skill on your profile.
In the mitochondrion sim, which structure is described as the site of oxidative phosphorylation?
In the glycolysis sim, the ATP (net) counter reads −2 after the second step. Why?
When the sim reaches pyruvate, the tally shows a net 2 ATP and 2 reduced NAD. How are the 4 ATP of this step made?
At the last step of the sim, the CO2 counter reads 6. Where were these released?
Each step removes carbon as carbon dioxide or hydrogen for NAD and FAD. Keep a tally per glucose: two pyruvates, so two link reactions and two turns of the cycle.
| Per glucose | CO2 | reduced NAD | reduced FAD | ATP |
|---|---|---|---|---|
| glycolysis | 0 | 2 | 0 | 2 (net) |
| link reaction (×2) | 2 | 2 | 0 | 0 |
| Krebs cycle (×2) | 4 | 6 | 2 | 2 |
| total | 6 | 10 | 2 | 4 |
The Krebs cycle itself makes very little ATP. Its main job is to supply reduced NAD and reduced FAD, whose hydrogen drives oxidative phosphorylation on the inner membrane.
Unlocks once the four checks above are done. Worth more XP, written to A Level Paper 4 standard.
What is the role of coenzyme A in aerobic respiration?
In the Krebs cycle, which molecule accepts the acetyl group and what is formed?
Which description of the link reaction is correct?
Why does pyruvate enter the link reaction only when oxygen is available?
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