Citric acid cycle and oxidative phosphorylation

The journey of glucose that began in the cytoplasm continues in the mitochondrial matrix, in the citric acid cycle (also called the Krebs or TCA cycle). It is the common final route for burning carbohydrates, fats and proteins.

• Acetyl CoA (2C) joins oxaloacetate (4C) to make citrate (6C).
• Citrate becomes isocitrate. Isocitrate dehydrogenase removes CO₂ and makes NADH, giving alpha-ketoglutarate (5C).
• The alpha-ketoglutarate dehydrogenase complex removes another CO₂ and makes NADH, giving succinyl CoA (4C).
• Succinyl CoA synthetase makes GTP: the cycle's only substrate-level phosphorylation.
• Succinate dehydrogenase, the one enzyme bound to the inner membrane, makes FADH₂.
• Fumarase and malate dehydrogenase (making NADH) rebuild oxaloacetate, ready for the next turn.

Each turn gives 2 CO₂, 3 NADH, 1 FADH₂ and 1 GTP.

Most ATP is made next, by the electron transport chain in the inner mitochondrial membrane. It has four complexes:

• Complex I (NADH-Q oxidoreductase): takes electrons from NADH.
• Complex II (succinate-Q reductase): takes electrons from FADH₂. It does not pump protons.
• Complex III (Q-cytochrome c oxidoreductase).
• Complex IV (cytochrome c oxidase): hands the electrons to oxygen, making water.

The small carrier ubiquinone (Q) ferries electrons from complexes I and II to complex III.

As electrons pass down the chain, complexes I, III and IV pump protons across the membrane, building a proton motive force. When the protons flow back through ATP synthase, it turns and makes ATP. One NADH gives about 2.5 ATP; one FADH₂ about 1.5, because its electrons skip complex I.