Into the mitochondrion: the Krebs' cycle

Aerobic respiration breaks food down completely, using oxygen, into CO₂ and water, and releases much more energy. In eukaryotes it happens inside the mitochondria. The pyruvic acid made in the cytoplasm is carried into them.

The link step. In the mitochondrial matrix, the enzyme pyruvic dehydrogenase, with the help of NAD⁺ and coenzyme A, removes one carbon from pyruvic acid as CO₂ and oxidises it (oxidative decarboxylation): pyruvic acid → acetyl CoA + CO₂ + NADH + H⁺. Since one glucose gives two pyruvic acids, this gives two NADH per glucose.

The Krebs' cycle (also called the TCA cycle or citric acid cycle), named after Hans Krebs, starts when acetyl CoA (2C) joins oxaloacetic acid (4C) and water to form citric acid (6C), the cycle's first product, using the enzyme citrate synthase. Citric acid becomes isocitrate, then loses two carbons as CO₂ in two steps, passing through α-ketoglutaric acid to succinyl-CoA.

When succinyl-CoA becomes succinic acid, a molecule of GTP is made directly, which then gives an ATP. This is substrate level phosphorylation. Further oxidation turns succinic acid back into oxaloacetic acid, which is ready to accept the next acetyl CoA. So the cycle keeps turning. In each turn, three NAD⁺ become NADH + H⁺, and one FAD becomes FADH₂.

Tally for one glucose so far: eight NADH + H⁺ and two FADH₂ made in the mitochondria (2 from the link step + 6 from the cycle), and 2 ATP from the cycle. Notice that oxygen has not been used yet. That comes in the next stage.