Chemiosmosis and the ATP payoff

The electron transport chain stores energy by crowding H⁺ into the intermembrane space. ATP synthase converts that stored energy into ATP, and in doing so it makes most of the ATP a cell gets from glucose.

Letting H⁺ back in

An H⁺ gradient is stored energy, like water held behind a dam. H⁺ tends to flow back into the matrix, down its gradient, and that flow releases energy. But the membrane’s lipid bilayer, the double layer of fatty molecules that forms the membrane, lets very little H⁺ through. The way back is through a channel in the membrane-embedded part of ATP synthase.

As H⁺ passes through, ATP synthase captures some of the released energy and uses it to join ADP and Pᵢ into ATP (ADP + Pᵢ → ATP + H₂O). The energy changes form, from an H⁺ gradient into the chemical energy of ATP. Making ATP with the energy of an H⁺ gradient is chemiosmosis (from the Greek osmos, “to push”).

Turning the rate up and down

Oxidative phosphorylation adjusts to the cell’s needs. Its rate depends on the supply of the chain’s substrates, NADH and O₂, and on the balance between ATP and ADP:

• When ATP is high, ATP binds to a subunit of cytochrome oxidase (complex IV), slowing the chain and, with it, ATP synthesis.
• When ADP is high, the process speeds up for two reasons: ADP stimulates cytochrome oxidase, and ADP (with Pᵢ) is the raw material for making ATP.

Glycolysis and the citric acid cycle have similar control points, and in all three stages, plenty of ATP puts on the brakes:

How much ATP per glucose

Oxidative phosphorylation can make at most 30–34 ATP from one glucose, while glycolysis and the citric acid cycle make only 2 each. That makes oxidative phosphorylation by far the cell’s biggest source of ATP.

That maximum is rarely reached, for two reasons:

• Cells use some of their NADH and FADH₂ in anabolic pathways, reactions that build larger molecules, such as the pathways that make certain amino acids. Those electrons never reach the chain.
• Mitochondria spend part of the H⁺ gradient on other jobs. For example, pyruvate enters the matrix through an H⁺/pyruvate symporter, a transporter that carries H⁺ and pyruvate across the membrane together.

Check yourselfA drug makes the inner mitochondrial membrane leaky to H⁺. Electrons still flow to oxygen. What happens to ATP production?

It drops sharply. H⁺ leaks back into the matrix without passing through ATP synthase, so the gradient can’t build up, and its energy is wasted instead of powering ATP synthesis.