Electron Transport Chain

or What about all this NADH?

If you have already visited the pages dealing with the Krebs Cycle, you should remember that the Krebs Cycle does not make much ATP and it uses no molecular oxygen. This appears contrary to the common knowledge that indicates that the Krebs Cycle is an aerobic process that makes ATP! How is this dilemma resolved? The answer lies in another pathway found in the mitochondrion, the electron transport chain (ETC).

As its names suggests, the ETC transports electrons through series of electron carrier proteins that are contained in one of four protein complexes embedded in the inner membrane of the mitochondrion. The four complexes are called I, II, III and IV (they have real names as well, but we do not need to deal with these here). Each carrier in these complexes is capable of accepting/donating 1 or 2 electrons at a time. Now, what do these electron carriers have to do with the Krebs Cycle and ATP synthesis?

As you should remember, the major product of the Krebs Cycle was the production of NADH. NAD accepted electrons (and energy) during the oxidation of acetyl CoA to carbon dioxide by the Krebs Cycle in the matrix of the mitochondrion. These NADH's take their electrons (and energy) to the ETC, specifically to Complex I of the ETC. The electrons (there are two electrons carried by each NADH) are transferred to an electron acceptor on Complex I and an NAD is regenerated as the NADH gives up its electrons. The NAD can now go back to the Krebs Cycle to pick up another pair of electrons. The electrons that were donated to Complex I now pass through series of proteins within the complex. Each time that the electrons are transferred, they lose some of the energy that they originally contained when with the NADH. (This is somewhat similar to a ball bouncing down steps, as it moves down, he amount of energy in the ball decreases and unless some energy is added to the ball, it will not go up the stairs). The energy that is released as the electrons pass through the electron carriers in Complex I is utilized to pump hydrogen ions (protons) across the inner mitochondrial membrane. Thus you should think of Complex I as an active transport system to move protons out of the mitochondrion (against a concentration gradient). The energy needed to do this comes from the energy that is with the electrons. Since the electrons (and the energy) ultimately come from the oxidation of acetyl CoA in the Krebs Cycle, the Krebs Cycle and ETC act together as the elaborate active transport system that moves creates a hydrogen ion concentration gradient across the inner mitochondrial membrane.

As electrons pass through the electron acceptors in Complex I, eventually they reach the final electron carrier in the protein complex. If left there, the electrons would quickly accumulate on all the carriers on Complex I until they were all filled with electrons. This is analogous to a sink with a stopper in the drain. Water would accumulate in the sink as there is no place for the water to go. At this point, no more electrons could pass from NADH to Complex I and the whole process would now grind to a halt. There must be a way for the electrons to be removed from Complex I. This is done by the presence of a small, lipophilic electron acceptor found in the inner membrane, known as Coenzyme Q or ubiquinone (ubi). Ubi accepts electrons and transports them to Complex III (this is not a misprint). Ubi is capable of moving in the membrane between Complex I and III, picking up electrons at Complex I and dropping them off at Complex III. As was the case with Complex I, Complex III contains a series of proteins that transport electrons. As the electrons are moved from carrier to carrier within Complex III, the energy that is released moves hydrogen ions out of the mitochondrion. Thus, Complex III also serves as a hydrogen ion pump. Once again, there must be a mechanism by which electrons are removed from Complex III. This done by a small peripheral membrane protein known as cytochrome c. Cytochrome c transports the electrons from Complex III to Complex IV. Complex IV, like Complexes I and III, transport hydrogen ions out of the mitochondrion as the electons move down the electron carriers.

By the time the electrons reach the final electron acceptor in Complex IV, they have very little energy left and need to be removed entirely from the system (otherwise the entire system will back up and be halted). Complex IV finally gives its electrons to molecular oxygen (O2), the final or terminal electron acceptor. The reduction of oxygen (remember, accepting electons is a reduction reaction) results in the formation of a water molecule from the oxygen. For every pair of electrons donated to the ETC by an NADH, O2 (or one O atom) is reduced to form one water molecule. Two NADH's would result in the use of 1 ( + ) O2 molelcule, and so on. If there was no oxygen to take the electrons from Complex IV, the electrons would accumlate up the electron transport chain very quickly and NADH would no longer be able to donate electrons to the ETC (because the ETC would be filled with electrons). This would cause an accumulation of NADH and a shortage of NAD (remember, NAD is regenerated when NADH donates its electrons to Complex I). Without NAD, there would be no electron acceptors for the Krebs Cycle and all reactions that require NAD would stop. This would cause the entire Krebs Cycle to stop. Thus the Krebs Cycle would not run if there were no oxygen present, thus it is considered aerobic!

Now, what about FADH?