ETC and Oxidative Phosphorylation

Question 1

Discuss what is happening biochemically with malignant hypothermia

Answer 1

Major inhalation anesthetics trigger a reaction in certain folks that results in the uncoupling of oxidative phosphorylation from electron transport. Because of this, ATP goes down, heat is generated, and the TCA cycle is stimulated leading to excessive CO2 and respiratory acidosis.

Question 2

How do we begin the electron transport chain?

Answer 2

We need to get the NADH and FADH2 into the inner mitochondrial membrane where the ETC is. FADH2 if you recall is made by an enzyme that resides here in the inner mitochondrial membrane so it just stays tightly boud, and easily enough, NADH can just readily go through the barrier.

Question 3

How does NADH unload its electrons for all of the fun stuff to happen?

Answer 3

NADH passes its electrons via the NADH dehydrogenase complex I to FMN.

FMN passes the electrons through a series of Fe-S complexes to Coenzyme Q, which accepts the electrons one at a time, making semiquinone and then ubiquinol

The energy used to transfer in this way is used to pump protons to the cytosolic side of the inner mitochondrial membrane

The protons then flow back into the matrix through special pores in the ATP synthase complex, generating a lot of ATP in the process.

Question 4

So now we have all of this action going on at Coenzyme Q. Where do the electrons go now? (That’s right, we’re not done yet)

Answer 4

Coenzyme Q passes electrons to Cytochromes b and c1 which pass lectrons to cytochrome c (this passing complex is known as the cytochome b-c1 complex or complex III.

We can only do one electron at a time (NADH had two, recall) due to Fe3+, the prostethic hand that does all the work in this complex, only being able to move one at a time (Fe3+ to Fe2+).

Just like before, the energy used to transfer electrons from Complex III to cytochrome c causes protons to go to the cytosol and then back again through the ATP synthase pores and create ATP.

Question 5

Wait, what happened to complex II, we jumped straight to complex III…

Answer 5

The succinate dehydrogenase enzyme complex for FADH2 is complex II, which wil ltransfer electrons to Coenzyme Q without the proton fun stuff.

Question 6

So now there is a big party happening on cytochome c, what do we do now?

Answer 6

The final bit is to get these guys to oxygen.

Cytochrome oxidase (complex IV) allows for the transfer of electrons from cytochrome c to cytochrome aa3 to oxygen, reducing it to water (you need 2 protons per oxygen, and since we have O2, we need 2 NADH worth of electrons to make one water).

This step also does the proton to and frow thing to make ATP.

Question 7

Important inhibitors of the Electron Transport Chain

Answer 7

Rotenone, amytal - Transfer of electrons from Complex I to FMN

Antimycin C - Transfer of electrons from complex III to cytochrome c

Carbon monoxide/Cyanide - Transfer of electrons from Complex IV to oxygen