Compared with fermentation, aerobic respiration gives access to much more of the free energy that is available from organic substrates such as sugars, fats and proteins. The complete catabolism of carbohydrates begins with the glycolytic pathway, but the pyruvate that is formed is then passed into the mitochondrion, where it is oxidatively decarboxylated to acetyl CoA. This, in turn, is then oxidised fully to CO2 by enzymes of the TCA cycle. Fatty acids are alternative substrates for energy metabolism in many cells.

Their catabolism occurs in the mitochondrial matrix and begins with ft oxidation to acetyl CoA, which then enters the TCA cycle. Proteins can also be used as energy sources, particularly under conditions of fasting or starvation. In such cases,proteins are degraded to amino acids, each of which is then catabolised to one or more end products that enter either the glycolytic pathway or the TCA cycle. Most of the energy yield from the aerobic catabolism of glucose is obtained as the reduced coenzymes (NADH and FADH2) are reoxidised by an electron transport system. This system consists of respiratory complexes that are large multi-protein assemblies embedded in the inner mitochondrial membrane (or, in the case of prokaryotes, in the plasma membrane).The respiratory complexes are free to move laterally within the membrane. Key intermediates in the electron transport system are coenzyme Q and cytochrome c, which transfer electrons between the complexes. In aerobic organisms, oxygen is the ultimate electron acceptor and water is the final product. Of the four main respiratory complexes, three (I, III, and IV) couple the transfer of electrons to the outward pumping of protons.

This establishes an electrochemical proton gradient that is the driving force for ATP generation. The ATP-synthesising system consists of a proton translocator,F0,embedded in the membrane, and an ATP synthase, F1,a knoblike structure that projects from the inner membrane on the matrix side (or on the cytoplasmic side of the plasma membrane in prokaryotic cells). ATP is synthesised by F1, as the proton gradient powers the movement of protons through F0. Thus, the electrochemical proton gradient and ATP are, in effect, interconvertible forms of stored energy. Mitochondria are the site of respiratory metabolism in eukaryotic cells and are prominent organelles in both size and numbers. Mitochondria may form large, interconnected networks in some cell types but are regarded here as discrete organelles. They are usually several micrometres long and range in abundance from one or a few up to hundreds or even a few thousand per cell.

A mitochondrion is surrounded by two membranes, the inner one having many infoldings, called cristae, that greatly increase the surface area of the membrane and hence its ability to accommodate the numerous respiratory complexes, FoF1, and transport proteins needed for respiratory function. The outer membrane of the mitochondrion is freely permeable to ions and small molecules due to the presence of porins. However, specific carriers are required for the inward transport of pyruvate, fatty acids and other organic molecules across the inner membrane of the organelle. ATP transport outward is coupled to the inward movement of ADP, and the concurrent inward movement of phosphate ions is coupled to the outward movement of hydroxyl ions, driven by the proton gradient. The electrons of coenzyme molecules that undergo reduction in the cytosol must be passed inward to the electron transport system by specific electron shuttle mechanisms because the inner membrane is not permeable to the coenzymes themselves.

This, then, is aerobic energy metabolism. No transistors, no mechanical parts, no noise, no pollution — and all done in units of organisation that require an electron microscope to visualise. Yet the process goes on continuously in living cells with a degree of integration, efficiency, fidelity and control that we can scarcely understand well enough to appreciate fully, let alone aspire to reproduce in our test tubes.