Citric Acid Cycle 3 - Online Tutor, Practice Problems & Exam Prep

The alpha-ketoglutarate dehydrogenase complex converts alpha-ketoglutarate to succinyl-CoA, utilizing cofactors like FAD, lipoate, and TPP, while reducing NAD⁺ to NADH. This reaction is a key driver in the citric acid cycle. The subsequent step, catalyzed by succinyl-CoA synthetase, involves substrate-level phosphorylation to produce GTP, which can be converted to ATP. The cycle continues with succinate dehydrogenase, producing FADH₂ and converting succinate to fumarate, with malonate acting as a competitive inhibitor. Understanding these processes highlights the interconnectedness of metabolic pathways.

Citric Acid Cycle 3

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, CoA and NAD⁺ as substrates. A lot of similarities here. Also, this guy's got that nice negative ΔG. Right? Again, this is one of the drivers of the citric acid cycle and we're going to take alpha-ketoglutarate and turn it into succinyl-CoA, 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⁺ 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 ΔG 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 breaking of the thioester bond is going to give roughly the amount of energy equal to the energy, uh-uh major energy differences here between input and output. Anyway, again this GTP, right? This GTP can be used to form ATP. I'm not showing it here, I showed it in the main citric acid cycle figure, but you know, it doesn't really matter for biochemistry because they're 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 ΔG of about 0. So again, it's just a quick conversion. It doesn't cost energy to 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 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, ΔG 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 trans form, 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 trans bond not a cis bond. That's the important thing to note. Also, kind of an 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. Malonate is a competitive inhibitor of, this enzyme. You can see malonate right there and you 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 the 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, the part of the reason I'm harping on this is, citrate also a molecule, right? But no, it is prochiral. So succinate not prochiral. Succinate is symmetrical but 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

Here’s what students ask on this topic:

What is the role of the alpha-ketoglutarate dehydrogenase complex in the citric acid cycle?

The alpha-ketoglutarate dehydrogenase complex plays a crucial role in the citric acid cycle by converting alpha-ketoglutarate to succinyl-CoA. This reaction involves the use of cofactors such as FAD, lipoate, and TPP, and it reduces NAD⁺ to NADH. The reaction is highly exergonic, with a negative ΔG, making it one of the key drivers of the citric acid cycle. This step is essential for the continuation of the cycle and for the production of energy in the form of NADH, which is later used in the electron transport chain to generate ATP.

How does succinyl-CoA synthetase contribute to ATP production in the citric acid cycle?

Succinyl-CoA synthetase catalyzes the conversion of succinyl-CoA to succinate, a reaction that involves substrate-level phosphorylation. During this process, the thioester bond in succinyl-CoA is broken, releasing energy that is used to convert GDP and inorganic phosphate (P_i) into GTP. GTP can then be readily converted to ATP by nucleoside diphosphate kinase, which has a ΔG close to zero, making the conversion energetically neutral. This step is important because it directly links the citric acid cycle to ATP production, providing a quick source of energy for the cell.

What is the significance of succinate dehydrogenase in the citric acid cycle?

Succinate dehydrogenase is a key enzyme in the citric acid cycle that catalyzes the conversion of succinate to fumarate. This reaction involves the reduction of FAD to FADH₂, which is later used in the electron transport chain to produce ATP. The reaction has a ΔG close to zero, making it readily reversible. An important aspect of this step is that it converts a single bond (succinate) to a double bond (fumarate), specifically forming a trans configuration. Additionally, succinate dehydrogenase is inhibited by malonate, a competitive inhibitor that closely resembles succinate in structure.

How does malonate act as a competitive inhibitor in the citric acid cycle?

Malonate acts as a competitive inhibitor of succinate dehydrogenase in the citric acid cycle. Its structure is very similar to that of succinate, differing only by the presence of one less CH₂ group. Because of this structural similarity, malonate can bind to the active site of succinate dehydrogenase, preventing succinate from binding and being converted to fumarate. This inhibition disrupts the citric acid cycle, as the conversion of succinate to fumarate is a crucial step for the production of FADH₂ and the continuation of the cycle.

What is the importance of GTP in the citric acid cycle and cellular metabolism?

GTP produced in the citric acid cycle by succinyl-CoA synthetase is important for several reasons. Firstly, GTP can be readily converted to ATP, providing a direct link between the citric acid cycle and ATP production. Secondly, GTP itself is used in various cellular processes, including protein synthesis. In mitochondria, which have their own DNA and protein synthesis machinery, GTP is particularly important. The ability to produce GTP ensures that the cell has a versatile energy currency that can be used for different metabolic needs.