Question

Certain drugs, which are called ionophores, cause the mitochondrial membrane to be highly permeable to \(\mathrm{H}^{+} .\) How would such drugs affect oxidative phosphorylation? a. Movement of electrons down the ETC would be inhibited. b. ATP synthesis would be inhibited. c. ATP synthesis would be unaffected. d. ATP synthesis would be stimulated. e. Both a and b would occur.

Short answer

The correct option is (b), ATP synthesis would be inhibited.

Step-by-step solution

Understanding Oxidative Phosphorylation

Oxidative phosphorylation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing energy which is used to produce ATP. During this process, electrons are transferred from electron donors to electron acceptors such as oxygen, in redox reactions. This process takes place in mitochondria.

Impact of Ionophores on Mitochondrial Membrane

Ionophores are substances that are able to integrate into cell membranes and allow specific ions to cross the membrane down their electrochemical gradient. In this case, the ionophores would cause the mitochondrial membrane to be highly permeable to \( \mathrm{H}^{+} \) ions. The flow of \( \mathrm{H}^{+} \) ions, also called protons, across the mitochondrial membrane provides the energy that drives ATP synthesis.

Effect on Oxidative Phosphorylation

If ionophores caused an increased permeability to \( \mathrm{H}^{+} \), it means there would be an increased flow of \( \mathrm{H}^{+} \) ions across the membrane. However, ATP synthesis relies on a controlled flow of \( \mathrm{H}^{+} \) across the mitochondrial membrane. If the mitochondrial membrane becomes highly permeable to \( \mathrm{H}^{+} \), it would disrupt this flow, leading to a dissipation of the proton gradient that is needed for ATP synthesis.

Key concepts

Mitochondrial Membrane Permeability

The mitochondrial membrane is critical for maintaining an environment conducive to ATP generation. In oxidative phosphorylation, mitochondria rely on the semi-permeability of their inner membrane to create a proton gradient. This gradient is a form of stored energy, harnessed to produce ATP. Imagine the membrane as a dam, with protons as water building up pressure. If this dam becomes highly permeable, the proton 'water' would simply flow through without generating power—in this case, ATP.

The controlled movement of protons across the mitochondrial membrane is the heart of the chemiosmotic theory, which describes how ATP is synthesized. The inner mitochondrial membrane normally allows a carefully regulated flow of protons back into the mitochondrial matrix, which drives the ATP synthase to convert ADP to ATP. When membrane permeability alters, so too does the entirety of this energy production process.

Ionophores Impact on Metabolism

Ionophores are like gate-crashers in the mitochondrial membrane's party. They disrupt the delicate balance of ion flow that mitochondria maintain. Specifically, when it comes to metabolism, the role of ionophores is to increase the permeability of the membrane to specific ions, such as protons (H+).

By allowing more protons to move freely across the membrane, ionophores effectively collapse the proton gradient. This action interrupts the usual metabolic processes that keep a cell powered. While ionophores can be useful in research for deliberately manipulating ion gradients, their disruptive nature on the mitochondrial membrane can lead to a metabolic quandary, stunting the cell's ability to generate ATP efficiently.

ATP Synthesis Inhibition

ATP synthesis is arguably the most critical step in a cell's energy provision. It is the culmination of a complex series of transactions in the electron transport chain and oxidative phosphorylation pathway. When ionophores increase the permeability of the mitochondrial membrane, they inhibit ATP synthesis. This is akin to removing the turbine from a hydroelectric power station; the potential energy is present, but no work is done to harness it into a useful form.

When discussing ATP synthesis inhibition, it is essential to recognize that the cell's energy economy hinges on the precise control of proton flow through ATP synthase. Any factor that undermines this control, such as the indiscriminate flow of protons enabled by ionophores, disrupts the cell's energy production.

Proton Gradient Dissipation

The dissipation of the proton gradient is a dire consequence of increased mitochondrial membrane permeability caused by ionophores. This gradient is a source of potential energy created by the separation of charges, with a higher concentration of protons in the intermembrane space than in the mitochondrial matrix. The dissipation is similar to a punctured balloon—the stored, potential energy rapidly escapes, and the proton gradient collapses.

Without a proton gradient, the force that drives protons through ATP synthase diminishes, curtailing ATP production. It's like standing in front of a deflating balloon and expecting a gust of wind strong enough to turn a wind turbine. The gradient's dissipation means the mitochondrial 'wind' fades, and so does the cell's ability to synthesize ATP from ADP and inorganic phosphate.