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

Answer:

A) Decreases cellular energy production

B) DCCD also affects K+ transport

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.