ATP Synthase and Chemiosmotic Coupling

MCAT Biochemistry

Sample MCAT Biochemistry Question

In terms of the proton gradient created during the oxidative phosphorylation, which of the following is true?

a) Low [H⁺] in the intermembrane space; High [H⁺] in the mitochondrial matrix

b) Low [H⁺] in the intermembrane space; Low [H⁺] in the mitochondrial matrix

c) Low [H⁺] in the mitochondrial matrix; High [H⁺] in the intermembrane space

d) High [H⁺] in the intermembrane space; High [H⁺] in the mitochondrial matrix

Click to Reveal the Answer

C is correct. Low [H⁺] in the mitochondrial matrix; High [H⁺] in the intermembrane space In oxidative phosphorylation, NADH and FADH₂ are oxidized to produce a proton gradient, and this proton gradient is used to produce ATP. The protons in this process are pumped from the mitochondrial matrix into the intermembrane space. Thus, there will be a high proton concentration in the intermembrane space and a low proton concentration in the mitochondrial matrix.

Oxidative Phosphorylation

Recall that oxidative phosphorylation, the process of oxidizing NADH and FADH₂ to power ATP, has two steps. The first step is the electron transport chain, where NADH and FADH₂ are oxidized to produce a proton gradient, and the second step is chemiosmotic coupling where ATP synthase utilizes the proton gradient to produce ATP. We explain how this latter step works in this post!

Chemiosmotic Coupling

In order to understand how the proton gradient generates ATP, it is first important to understand the basic concepts involved in the transfer of ions. Chemiosmotic coupling is one such concept that is important to understand for the MCAT exam. Chemiosmotic coupling is based on the chemiosmotic theory, which states that the energy produced from oxidizing NADH and FADH₂ is stored as a proton concentration difference across the inner mitochondrial membrane.

Recall that protons are pumped from the mitochondrial matrix to the intermembrane space during the electron transport chain. This movement of protons creates a high proton concentration in the intermembrane space and a low proton concentration in the mitochondrial matrix. The energy stored in the proton concentration difference is also called the proton motive force. This proton motive force is what will be used to produce ATP. (Figure 1).

The reason why the proton gradient can power so much ATP production is because it stores both chemical potential energy and electrical potential energy. The chemical potential energy is due to the concentration difference across the membrane (recall that chemicals naturally want to flow from a higher concentration to a lower concentration) (Figure 1) and the electrical potential energy refers to the charge difference between the mitochondrial matrix and the intermembrane space. By pumping positive charges into the intermembrane space, the mitochondrial matrix carries a net negative charge in comparison to the intermembrane space. In this way, the mitochondrial matrix will be able to attract positive charges as a result of stored up electrical potential energy, motivating protons to move back into the matrix.

ATP Synthase

The formation of ATP from ADP and inorganic phosphate is an energetically unfavorable reaction. By coupling ATP synthesis with an electrochemical gradient, an energetically unfavorable, endergonic reaction is paired with an energetically favorable, exergonic one. Figure 2 illustrates a special protein pore in the inner mitochondrial membrane called ATP synthase. The function of ATP synthase is to couple the favorable movement of protons down their concentration gradient with the unfavorable synthesis of new ATP molecules.