Structures of the Citric Acid Cycle: Study with Video Lessons, Practice Problems & Examples

The Citric Acid Cycle, also known as the Krebs cycle, begins with oxaloacetate, a 4-carbon compound, which is converted into citrate. Key metabolites include isocitrate, alpha-ketoglutarate, and succinyl CoA, with each containing carboxyl groups, except succinyl CoA. The cycle regenerates oxaloacetate from malate, completing the process. Memory tools, such as mnemonic phrases, aid in recalling the sequence of intermediates: oxaloacetate, citrate, isocitrate, alpha-ketoglutarate, succinyl CoA, succinate, fumarate, and malate. Understanding these structures and transformations is crucial for grasping metabolic pathways and energy production.

Citric Acid Cycle Structures Concept 1

Everyone, now let's talk about the structures of the Citric Acid Cycle. Now, here we're going to say that the Citric Acid Cycle begins with Oxaloacetate, which is composed of 4 carbons. And here there are 2 big hints that we can rely on to help us have a general idea of a majority of the metabolites within the citric acid cycle. Hint 1 says that all metabolites contain carboxylate groups on both ends of their molecules, except for succinyl CoA. So when we get succinyl CoA, it'll be the odd one out.

Our second hint, we have citrate and isocitrate. So, notice the names. Citrate, isocitrate. So, there must be some relationship between them.

Well, they contain an extra carboxylate group, which makes them tricarboxylic acids. Right. So, those are the 2 big hints that we're going to start out with when it comes to these structures. And then we'll talk about other types of memory tools that we can employ to help us remember the general structures of each of the metabolites of the Citric Acid Cycle.

Citrate Formation Concept 2

Let's take a look at Phase A of the citric acid cycle. Here, we're talking about citrate formation. Here, oxaloacetate is converted into citrate. Now, remember we said that oxaloacetate starts off the citric acid cycle and that it has 4 carbons. Also, remember for hint 1, we said that all these metabolites except for succinyl CoA have 2 carboxylate groups.

They're on both ends of these metabolites. So we'd have a COO^- here and a COO^- here. Let's look at the memory tool to help us figure out the rest of this structure. Oxa of oxaloacetate stands for ketone. Oxa is green, which would mean that this green carbon would be a carbonyl.

Acetate is CH₃COO^-, which is this part here in red. We have to change the CH₃ to a CH₂, otherwise, carbon would be making too many bonds. So this represents the structure of Oxaloacetate. Now, it is converted into citrate within phase A. So what does citrate look like?

Well, here for citrate, we're going to add an acetate group to carbon 2 of oxaloacetate. So if I'm numbering this, this is 1, 2, 3, and 4. We just said what an acetate is, so CH₂COO^-.

I just added it to carbon 2. Now that carbon there was a carbonyl, that green carbon. That oxygen is still there. And remember, when we're adding something, a group, a nucleophile to a ketone, that's a way of changing that ketone into an alcohol. So this is an OH group.

And just remember, citrus, citric citrate, citrus fruits are acidic in terms of taste when you bite into them. So 3 acidic bites equals 3 carboxyl groups or carboxylic acid groups. Remember hint 2 said that citrate and isocitrates have an additional carboxyl group, which makes them tricarboxylic acids in nature. So we have 1, 2, 3 carboxyl groups there. Alright.

So we just drew the first two metabolites of the citric acid cycle based on the hints that we talked about previously and these memory tools that we have here. So, click on the next video and let's continue our discussion of the structures of the TCA cycle.

Citrate Formation Example 1

In this example, it says, determine the type of chemical reaction in the transformation of oxaloacetate to citrate. Alright. So what exactly happened? Well, to go from oxaloacetate to citrate, we added an acetate group to carbon number 2. Now remember, carbon number 2 of oxaloacetate is a ketone.

What do we call a reaction where a nucleophile, in this case, the acetate group, gets added to a ketone? That's right. Remember, ketones and aldehydes undergo nucleophilic addition reactions. So that means the answer here will be option B. We had a nucleophilic addition type of reaction that helped us transform oxaloacetate to citrate.

We did this by adding an acetate group to carbon 2 of the oxaloacetate molecule. So again, our final answer here is option B.

Succinyl CoA Formation Concept 3

Alright, let’s take a look at phase B, where we have succinyl CoA formation. Remember, citrate was formed at the end of phase A. Now from citrate, we go to reaction 2, which helps to produce isocitrate. The names are very similar.

That's because they're isomers of one another. Our memory tool here is that it is a C2, C3 isomer of citrate. So, if we say that this is 1, 2, 3, 4, 5, it is a C2, C3 isomer of citrate. That just means the OH comes down here, and now it's on carbon 2, and the H comes here. This will become more important later on.

Notice that we've gone from a tertiary alcohol to a secondary alcohol. Remember, secondary alcohols can be oxidized, whereas tertiary alcohols cannot. Now, if we go to reaction 3, isocitrate becomes alpha-ketoglutarate. How do we draw alpha-ketoglutarate? Our memory tool here is "alpha alpha," and keto is because it's a ketone.

It is an alpha ketone. Remember, carboxyl groups, carboxylic acid groups have the highest priority, so this is 1. The carbon next to it would be our alpha carbon, and we just said it's an alpha ketone, so we just make this here a ketone. So this would be the structure of our alpha-ketoglutarate. Now, here with succinyl CoA, this represents reaction 4, or step 4, where we go from alpha-ketoglutarate to succinyl CoA.

Here, we're going to say it's the fourth step, so there are 4 carbons within it. Notice that we have lost our carboxyl group as we go from isocitrate to alpha-ketoglutarate. Remember, hint 2 said that the only tricarboxylic acids are citrate and isocitrate. So that carboxyl group had to go. By the time we get down to succinyl CoA, we only have 4 carbons left.

These 4 here. And then we're going to say that we would add CoA at carbon 4. So, we put CoA here. So this will represent succinyl CoA. Remember succinyl CoA, the fourth reaction.

A lot of fourth involved: fourth step, 4 carbons, CoA goes to carbon 4. Alright. So this is what we’d say in terms of this structure here.

Just keep in mind these different memory tools as well as some of the hints 1 and 2 that we talked about earlier to describe the structures in phase B of the Citric Acid Cycle.

Succinyl CoA Formation Example 2

Which of the following accurately describes the transformation of alpha-ketoglutarate to succinyl CoA? Alright. So remember, what's really happening here with alpha-ketoglutarate to succinyl CoA? So here, for alpha-ketoglutarate, we had a carboxyl group here. And going to succinyl CoA, that carboxyl group is lost and instead we add an S CoA to that carbon.

Now, we're going to say here that sulfur has a higher oxidation number than carbon, so that carbon's becoming oxidized by forming that connection to sulfur. Here, it was carbon on carbon, but now it's carbon and sulfur. So we'd say that this represents an oxidation reaction. We've replaced the less electronegative carbon of this carboxyl group with the more electronegative sulfur here. This causes a greater imbalance between carbon and sulfur, so that's going to be an oxidation in essence.

So, here again, our final answer would be option C.

Oxaloacetate Regeneration Concept 4

Now take a look at phase c of the citric acid cycle where we have oxaloacetate regeneration. Here, we're going from succinate to fumarate to malate. We're going to say that at the end of the cycle, malate is oxidized to reform oxaloacetate. Remember, at the end of phase b of the citric acid cycle, we created succinyl CoA. Succinyl CoA would then go into reaction 5 to help us create succinate, which starts off phase c of the citric acid cycle.

Remember, our hint 1 is that all the metabolites have carboxyl groups on both ends of their molecules except for succinyl CoA. So going from succinyl CoA to succinate would mean we reestablish the dicarboxylic acid theme of the metabolites. And that's why the memory tool is "remove CoA". So here we have succinate, then we go to reaction 6 which changes succinate to fumarate, here, and then malate. The hint is memory tool, flat molecule.

Fumarate is a flat molecule. This talks about the planarity around the alkene carbons. Remember, alkene carbons have an sp2 hybridization and therefore are trigonal planar, which means they're flat. So here we have an H and here we have an H. Going from Succinate to Fumarate, we create a pi bond between these two carbons.

As a result of this, we lose hydrogens. Alright. So now we have fumarate, and in reaction step 7, we're going to change fumarate into our malate. So here we're finally making malate. And our memory tool here is "moisturized malate".

We're moisturizing something. We're adding water to it. So if we're adding water to this thing, we're hydrating it. So think of it as a hydration reaction. We added an H and an OH.

So that's how we create malate. And then finally, malate is going to be changed into oxaloacetate, which we've talked about before in the past. In the beginning, we have to have a ketone. So here's our ketone here. So we've oxidized our alcohol to a carbonyl group. So this is our oxaloacetate, starting the whole process again. Alright. So these represent the hints that we need to use, as well as these memory tools to draw each of the metabolites of phase c of the Citric Acid Cycle.

Oxaloacetate Regeneration Example 3

In this example, it says, "Which of the following compounds represents a tricarboxylic acid?" Now, remember we have hints when it comes to the structures of the metabolites of the citric acid cycle. Hint 1 said that all of them contained 2 carboxyl groups except for succinyl CoA. And hint 2, which is what we're going to use here, is that 2 of the metabolites had an additional carboxyl group making them tricarboxylic acids in nature. We're going to say those 2 metabolites would be citrate and isocitrate.

Remember, we use the memory tool of citrus; 3 acidic bites equal 3 carboxylic acid groups. If we take a look here, the only citrate we have is isocitrate, which is one of the two. Our answer here would be option D. Hint 2 told us that isocitrate and citrate were the 2 metabolites that possessed an additional carboxyl group, making them tricarboxylic acids. So, again, our final answer again is option D.

Which reactions of the citric acid cycle involve a decarboxylation?

• A. Reactions 1 and 2
• B. Reactions 2 and 4
• C. Reactions 3 and 4
• D. Reactions 3, 4, and 7
• E. Reactions 2, 5, and 6

Remembering Citric Acid Cycle Concept 5

Now when it comes to remembering the citric acid cycle, just recall that each reaction of the citric acid cycle can be remembered by memorizing the intermediate metabolite names. Here, a memory tool is Oxford City, ice crates, kegs, and such contain succulent foamy milk. Alright. So how does this work? Okay.

So Oxford. So we're talking about oxaloacetate here. Remember that's produced in reaction 8. We're going to say acetyl-CoA is coming in, and together they're going to help to make our citrate. Citrate city.

Then we're going to go to reaction 2, where citrate is going to become isocitrate, ice crates. Then going from isocitrate, reaction 3, we're going to kegs, which is alpha-ketoglutarate. Then we're going to say going to 4, alpha-ketoglutarate is going to become succinyl-CoA. So such succulent oh no. Such contain, so succinyl-CoA.

Then in reaction 5, succinyl-CoA becomes succinate, so succulent succinate. Then we're going to say that it's going to undergo an oxidation, where succinate is going to become fumarate, foamy. Then we're going to say here, in reaction 7, we're going to say that fumarate becomes malate, milk. And then finally, reaction 8 is where we go from malate to oxaloacetate. So remembering this memory tool is just helping us remember the order of each one of these compounds, and the reactions for the citric acid cycle.

Remembering Citric Acid Cycle Example 4

Here in this example, it says, "Write the name for the substrate and product of reaction 6 of the citric acid cycle." Now, reaction 6 of the citric acid cycle represents the first reaction of phase c. In phase c, we go from succinate, because we've reestablished our dicarboxylic acid structure, and we create a pi bond between our carbons to create fumarate, which is a flat molecule. So here, the answer would be option b. We're going to go from succinate, which represents our substrate, to fumarate, which represents our product.

So again here, the answer would be option b.

Identify the reaction that involves an isomerization reaction between the substrate and product.

• A. Reaction 1 
• B. Reaction 3 
• C. Reaction 8
• D. Reaction 2 
• E. Reaction 4

Identify the reaction that involves the creation of a product with planarity.

• A. Reaction 1
• B. Reaction 6
• C. Reaction 8
• D. Reaction 2
• E. Reaction 4