Question

DCCD (dicyclohexylcarbodiimide) inhibits oxidative phosphorylation when the substrate is mitochondrial NADH. DCCD is a drug that binds to ATP synthase and blocks proton transport through the ion channel. A) Explain what the consequences are of DCCD on cellular energy production. B) Suggest at least one other cellular effect of DCCD, and prepare an explanation of this effect.

Answer 1

DCCD binding to ATP synthase leads to decreased ATP production and could affect other cellular processes reliant on ATP for energy. Cyanide poisoning would increase the pH of the intermembrane space and stop ATP synthesis.

Step-by-step explanation:

Consequences of DCCD on Cellular Energy Production

When DCCD binds to ATP synthase, it prevents proton transport through the ion channel which is crucial for the production of ATP during oxidative phosphorylation. This inhibition leads to a decreased production of ATP, which is the main energy currency of the cell. As a direct consequence, cells would have less energy to perform vital functions, leading to cellular dysfunction or death if ATP levels fall too low.

Other Cellular Effects of DCCD

Beyond the reduction in ATP synthesis, DCCD can influence other cellular processes that are energy-dependent. One effect could be the inhibition of active transport mechanisms across the cell membrane that require ATP. Cells would struggle to maintain proper ion gradients, which are essential for various physiological processes, including nerve impulse transmission and muscle contraction.

Example of Oxidative Phosphorylation Inhibition

Regarding cyanide, which is another inhibitor of the electron transport chain, if cyanide poisoning were to occur, one would expect the pH of the intermembrane space to increase (become less acidic) because proton pumping would be halted. The lack of protons in the intermembrane space would directly halt ATP synthesis, as the proton gradient is necessary to drive the phosphorylation of ADP to ATP.

Answer 2

A) Decreases cellular energy production

B) DCCD also affects K+ transport

Step-by-step explanation:

A) Consequences are of DCCD on cellular energy production: Decreases cellular energy production

ATP-synthase pump is composed of two subunits: F1 catalytic subunit that synthesizes ATP, and F0 proton pumping subunits, that transport H+ through the membrane. F1 subunit might act independently of F0 to produce ATP, but this molecule can not be released without H+ gradient, which generates a movement necessary for ATP release from the catalytic center.

When any of the parts composing F0 react with DCCD, the subunit can not transport H+ through the membrane. DCCD inhibits the enzyme activity by blocking the protons´ flow.

As DCCD blocks the protons´ flow, and the protons´ flow is necessary to release the ATP molecule from the F1 subunit, no other ADP + Pi can enter to F1 subunit, and the production of ATP stops.

B) Other cellular effects of DCCD

There seem to be other effects of DCCD on cell activity, some of which are still under study. To name a few:

• Diimide from DCCD seems to stimulate cytochrome b reduction and inhibits its reoxidation by ferricyanide.
• When exposing the cell to high concentrations of DCCD for a long time, might occur an alteration in the electron transporting chain
• Inhibition of ubiquinol-cytochrome c reductase activity when exposing the cell to high concentrations of DCCD.
• Inhibition of K+ transport, associated with the inhibition of H+ transport.

Concerning the effect of DCCD on the K+ transport, DCCD stops the extrusion of H+ and the consequent intrusion of K+.

DCCD strongly inhibits the simultaneous flow of H+ and K+. First, it inhibits H+ flow, acidification of the environment stops, but at this point, K+ keeps moving through the membrane. Once the H+ flow has ceased, the K+ flow slowly decreases until it finally stops moving. There is a lag time in the DCCD effect on K+ flow to the instantaneous effect on H+ flow.