Oxidative Phosphorylation 3 - Online Tutor, Practice Problems & Exam Prep

The electron transport chain consists of four complexes that facilitate oxidative phosphorylation. Complex I (NADH dehydrogenase) and Complex III (cytochrome b) pump protons into the intermembrane space, while Complex II (succinate dehydrogenase) does not pump protons but transfers electrons to ubiquinone. Complex IV (cytochrome c oxidase) uses electrons from cytochrome c to reduce oxygen to water, completing the process. This series of redox reactions generates a proton motive force, essential for ATP synthesis through chemiosmotic theory, highlighting the interconnectedness of metabolic pathways.

Oxidative Phosphorylation 3

Let's take a closer look at what's going on inside the complexes of the electron transport chain. Complex I, which is also called NADH dehydrogenase, pumps 4 protons into the intermembrane space, and it has the prosthetic groups, flavin mononucleotide and iron-sulfur proteins. Now NADH delivers 2 electrons to complex I, and it passes them on to flavin mononucleotide and then they move on to the iron-sulfur ubiquinone which also takes 2 protons out of the intermembrane space. And then it gets reduced and it will go on to complex III. But we will get to that in a moment. First, let's take a look at complex II, which is succinate dehydrogenase. So, this is actually an enzyme that is also part of the citric acid cycle if you might remember, and it doesn't pump any protons. It does however contribute slightly, if you think about it because it is going to also pass its electrons onto ubiquinone. And ubiquinone is going to pull 2 protons out of the mitochondrial matrix. So even though it doesn't pump any protons, it is going to remove protons. Okay. So it actually has FAD as a prosthetic group. I know the image looks as though FAD or FADH₂ is external to the protein complex but it's actually part of the protein complex. So it's a prosthetic group, right? The reaction with succinate dehydrogenase is going to pass electrons to FADH₂, and it is going to pass electrons onto those iron-sulfur proteins. And, FADH₂ again will deliver its electrons to ubiquinone which will become reduced and go on to complex III. Now, it's interesting to note that there are actually 3 FAD entry points to ubiquinone, right? We have complex II which we talked about. But we can also send FAD to ubiquinone through beta oxidation, and if we use that system we talked about just previously where NADH will actually pass its electrons onto an FAD which gives them to ubiquinone, right? So there's actually three ways for FAD to give electrons to ubiquinone. And complex II is only one of them. So just something to think about.

Now Complex III, or cytochrome B as it's sometimes called, pumps 4 protons into the intermembrane space and has a heme prosthetic group and iron-sulfur proteins. And it actually has a pretty interesting thing that occurs with ubiquinone called the Q cycle where essentially cytochrome C, which is ultimately what's going to receive the electrons from ubiquinone, can only accept one electron at a time. It can only move one electron at a time. Ubiquinone passes on 2 electrons at a time though. It actually has to pass on 2 at a time. It can't hold on. So essentially what happens is you have just one reduced ubiquinone come in and drop both of its electrons off. And one goes to the iron-sulfur proteins and onto cytochrome c. The other takes a different route where it actually links up with another ubiquinone that gets reduced and actually comes back and drops off its electrons So this cycle continues. So after this, you'd have another ubiquinone come in and this would repeat. But we're not actually being shown that in the figure. We're just being shown the net reaction for 2 electrons, right? Because we had 2 electrons coming in from complex I or II, so we want to follow their path through. So the net reaction of those 2 electrons coming in and those 2 electrons leaving via 2 cytochrome c is 4 protons get pumped through. And ubiquinone while it is performing this Q cycle, right? The ubiquinones that pick up that extra electron are going to end up taking 2 protons out of the mitochondrial matrix. So from here, cytochrome c is going to bring the electrons to their final stop which is complex IV or cytochrome c oxidase.

Now, this is going to pump 4 protons as well. Essentially the electrons are going to move from cytochrome c to these 2 coppers. You have these 2 coppers in complex IV. They are going to accept the electrons from cytochrome c. What I am showing here is significant in a second, right? So now we're talking about what would have been delivered from 2 NADH or FADH₂. And this is important to the numbers matching up to the reaction below we're going to talk about. Anyhow, you have cytochrome c dropping off those electrons to the coppers. They move through complex IV. What you wind up with is water being formed. So Complex IV is going to take in protons and oxygen, and it is going to form water. So, oxygen is the final electron acceptor here, and it enters its most reduced form as water and that is the end of Electron Transport. I mean, you got to think about this for a second. It's pretty amazing that, you know, this oxygen right here is the reason that we're exhaling is the CO₂ that's coming off of the reactions in the citric acid cycle. I mean that's pretty mind-boggling, right? I just think it's so cool. Anyhow, with that, I'm done geeking out and let's flip the page.

Here’s what students ask on this topic:

What is the role of Complex I in the electron transport chain?

Complex I, also known as NADH dehydrogenase, plays a crucial role in the electron transport chain by transferring electrons from NADH to ubiquinone. It contains prosthetic groups such as flavin mononucleotide (FMN) and iron-sulfur (Fe-S) proteins. NADH donates two electrons to FMN, which then passes them to the Fe-S clusters. These electrons are ultimately transferred to ubiquinone, reducing it to ubiquinol. During this process, Complex I pumps four protons (H⁺) from the mitochondrial matrix into the intermembrane space, contributing to the proton motive force essential for ATP synthesis.

How does Complex II differ from Complex I in the electron transport chain?

Complex II, or succinate dehydrogenase, differs from Complex I in several ways. Unlike Complex I, Complex II does not pump protons into the intermembrane space. Instead, it transfers electrons from succinate to ubiquinone via FADH₂ and iron-sulfur (Fe-S) proteins. Complex II is also part of the citric acid cycle, where it catalyzes the oxidation of succinate to fumarate. The electrons from FADH₂ are passed to ubiquinone, reducing it to ubiquinol, which then moves to Complex III. Although Complex II does not contribute directly to the proton gradient, it plays a vital role in electron transfer within the chain.

What is the Q cycle in Complex III of the electron transport chain?

The Q cycle is a mechanism in Complex III (cytochrome b) that facilitates the transfer of electrons from ubiquinol (QH₂) to cytochrome c. Ubiquinol donates two electrons: one electron is transferred to cytochrome c via iron-sulfur (Fe-S) proteins, while the other electron takes a longer route, reducing another ubiquinone molecule to ubiquinol. This process results in the pumping of four protons (H⁺) into the intermembrane space, contributing to the proton motive force. The Q cycle ensures efficient electron transfer and proton pumping, essential for ATP synthesis.

What is the final electron acceptor in the electron transport chain?

The final electron acceptor in the electron transport chain is molecular oxygen (O₂). In Complex IV (cytochrome c oxidase), electrons from cytochrome c are transferred to oxygen via copper (Cu) and heme groups. Oxygen is reduced to water (H₂O) by accepting electrons and protons. This reaction is crucial as it ensures the continuation of electron flow through the chain, maintaining the proton gradient necessary for ATP synthesis. The reduction of oxygen to water also prevents the accumulation of electrons, which could otherwise lead to the formation of harmful reactive oxygen species (ROS).

How does the proton motive force drive ATP synthesis in oxidative phosphorylation?

The proton motive force (PMF) is generated by the pumping of protons (H⁺) into the intermembrane space by Complexes I, III, and IV of the electron transport chain. This creates an electrochemical gradient across the inner mitochondrial membrane. ATP synthase, an enzyme embedded in the membrane, utilizes this gradient to synthesize ATP from ADP and inorganic phosphate (P_i). As protons flow back into the mitochondrial matrix through ATP synthase, the energy released drives the phosphorylation of ADP to ATP. This process, known as chemiosmosis, is essential for cellular energy production.