Citric Acid Cycle 3 - Video Tutorials & Practice Problems
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Citric Acid Cycle 3
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Next on deck, alpha ketoglutarate dehydrogenase complex. It's another complex and it's a lot like pyruvate dehydrogenase complex. It uses the same cofactors, FAD, lipoate and tpp, And it also uses, co a and n a d plus as substrates. A lot of similarities here. Also, this guy's got that nice negative delta g. Right? Again, this is one of the drivers of the citric acid cycle and we're gonna take alpha ketoglutarate and turn it into succinylcoa, this molecule right here. And, during the course of this reaction we are decarboxylating. Right? We are decarboxylating this guy coming off. Add CoA in. You can see CoA right there. Oops, sorry. I didn't jump out of the way. You can see CoA right there in our product. That was the weirdest arrow I've ever drawn. There we go. There's CoA. NAD plus comes in, gets reduced to NADH. Guess what? That is what's going on with FAD. Remember what was happening with pyruvate dehydrogenase? Yeah. Again, biology conserves things. You can see a lot of stuff. A lot of similar processes and whatnot recycled all the time. It's just another example. Another in a long series I might add. So, step 5, succinyl CoA synthetase. It's got a a delta g close to, close to 0. And so this is going to be one of those readily reversible reactions. The thioester bond is broken. And that is going to supply the energy to make that GTP, right? To do the substrate level phosphorylation to combine GDP and inorganic phosphate to form GTP. This is that thioester bond breaking is going to give roughly the amount of energy equal to the energy uh-uh major energy differences here between input and output. Anyways, again this GTP, right? This GTP can be used to form ATP. I'm not showing it here. I showed it in the the main citric acid cycle figure, but you know, it doesn't really matter for biochemistry because they're, you know, equivalent in terms of their energy value. But we can make ATP from it and if we did that, we'd be using this nucleoside diphosphate kinase and, you know, that's got like a delta g of about 0. So again it's just a quick conversion. It doesn't cost energy the cell. The difference really is that, you know, ATP and GTP are used for different things. GTP very importantly is used for protein synthesis. And, hopefully you guys remember from intro bio, mitochondria have their own DNA, right? Getting to back to endosymbiotic theory, mitochondria were thought to once be autonomous cells that lived outside of what are now eukaryotic cells and that they fused with these larger cells to form eukaryotic cells, but they still retain their own DNA and they still carry out their own protein synthesis which is why they need some GTP. Not all the genes that mitochondria require are actually stored in the nucleus of the cell, they carry some of their own. Pretty pretty cool, I have to say. Succinate dehydrogenase, step 6. This is where we make our FADH2, the one and only. Again, delta g about 0. We go from succinate to again blocking this molecule to fumarate right here. This reaction, basically converts an -ane, right? This -ane right here to this -ene we see right here. And what's important to note is that this is the transform so, this drawing is, you know, a little weird but, cause you know we're showing like a Fisher structure but hopefully you can see that this is a trans bond. So if I were to redraw it, we'd have our COO here and COO there. Let me put my minus signs in. So this is a transbond not a cis bond. That's the important thing to note. Also kind of interesting thing to take note of is, the inhibitor of this enzyme, malonate. Malonate. This is malonate not so different molecules, right? Malate is going to be one of the substrates of the citric acid cycle. Malinate is not. Malinate is a competitive inhibitor of, this enzyme. You can see malinate right there and might notice that its structure is very very close to succinate, right? These two molecules here and here, they look very similar. The difference is really just the presence of 1 CH2. So you get rid of that, you have malonate. So, malonate acts as a competitive inhibitor, for succinate. So, last thing I want to mention about this is getting back to what I, you know, went on and on about how succinate is symmetrical, so its orientation into the active site of succinate dehydrogenase will be random. And, just remember, you know, the part of the reason I'm harping on this is, citrate also molecule, right? But no, it is prochiral. So succinate not prochiral. Succinate is symmetrical but it's not prochiral and its orientation will be it's not prochiral and its orientation will be randomized into succinate dehydrogenase. And so if we have labeled carbons, they can wind up here or they can wind up here. And, if we have labeled carbons, only half will come out every round of the citric acid cycle. So we'll get half out the first round then a quarter and then an eighth, and so on and so forth. We keep doing more rounds without putting any more labeled carbon in. Alright. With that, let's actually turn the page and finish up the