Citric Acid Cycle 2 - Video Tutorials & Practice Problems
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Citric Acid Cycle 2
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Alright. Step 1 of the citric acid cycle is carried out by citrate synthase and notice that nice negative delta g. Remember, this is one of those driving steps of the citric acid cycle. And in the process of this reaction, we have our acetyl CoA oxaloacetate. We add water in. We bump off that CoA. See you later. And we are left with citrate right here. Now, the following reaction, reaction number 2 is carried out by aconitase. And you might notice that it it's listed as having a positive delta. Notice though that that's the, delta prime naught. At actual cellular conditions, this delta G is closer to 0. It's a readily reversible reaction. Here citrate is going to be, turned into this enzymatic intermediate, cis aconitate which you can see right here in the middle and Then ultimately it's turned into isocitrate. During this process, we remove water and then we actually add water back in. That is why again sometimes called the Ferris wheel. It is kind of like doing a turn. What is interesting to note and also important to note about this reaction is that citrate is prochiral. What that means is that, even though it's not actually a chiral molecule, it behaves as if it were chiral and that's because aconitase aconitase binds citrate in one orientation. It's it's just, you know, it just happens this way. It's not you don't need to know why this is but just notice that, this is a also symmetric molecule. I mean this right here, that's just same as CH2, right? They're just drawing it out. So this is not a chiral center. However, you know, like right here is always where this double bond is going to be formed. You know, the the citrate wouldn't go in in the other orientation and have it be formed there. It just happens that way and we call that property prochiral meaning not actually chiral but behaving as if it were chiral. Something about aconitase that's interesting to note is it it contains these iron sulfur complexes, which are actually held into the enzyme, by cysteine residues. And this is not going to be the last time we talk about iron sulfur complexes. Those are going to come up in the next review when we talk about the electron transport chain because there's a ton of them in there. And what's what's cool about acontase in terms of these iron sulfur complexes is it it's actually an iron response regulatory molecule. So when there is a lack of iron, it's going to change when it changes shape due to this lack of iron excuse me. It can actually bind RNA. And if it binds RNA, it will, you know, turn on and off various genes and what's going to happen is when iron is high in the blood, ferritin, this molecule ferritin is going to be produced. And when iron is low in the blood, this molecule, transferrin, is going to be produced. So kind of cool. Aconitase has this auxiliary function, right? It's not just an enzyme that's part of the citric acid cycle and again, this kind of continues the theme that biology recycles things, right? It it always finds new purposes for old creations. It's always innovating. So 3rd reaction of citric acid cycle is iso, carried out by isocitrate dehydrogenase. We are going to take isocitrate form alpha ketoglutarate which I am blocking right now. Beautiful. Alpha ketoglutarate, alpha KG. I'm just abbreviating it that way because I'm being lazy. Now kind of a couple interesting notes about this reaction. As we've already said, it generates NADH and releases a CO2. You know, definitely important to note. Also, just to be crystal clear, here is our CO 2 that's coming off. So that is our released CO 2. And you know that makes this enzyme an oxidative decarboxylase. Notice how we are oxidizing that alcohol. And it uses NAD plus or NADP plus as the electron acceptor. However, for, you know, for us, for humans, we're going to be using NADH to generate I'm sorry, NAD plus to generate NADH. And, it also uses manganese as a cofactor. It does not use even though it's a dehydrogenase. So, you know, we're gonna talk about a couple dehydrogenases here. First one was pyruvate dehydrogenase. This is our second, right, isocitrate dehydrogenase but this one is not going to use TPP, lipoate, and FAD, and co a. It's not going to use those molecules like pyruvate dehydrogenase did. However, alpha ketoglutarate dehydrogenase which we're going to talk about in just a moment is going to use, all this stuff which is why I point out here that isocitrate doesn't use it, right? Isocitrate doesn't use it but pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase do use this stuff. So, don't go thinking like all dehydrogenases are using, those same molecules. All right. With that, let's flip the page.