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

The citric acid cycle, also known as the Krebs cycle, begins with Acetyl CoA and produces energy-rich molecules: 1 GTP, 3 NADH, and 1 FADH₂. It involves a series of oxidation reactions, generating CO₂ and reducing NAD⁺ to NADH, which is crucial for the electron transport chain. Although the cycle does not directly use oxygen, it is classified as aerobic because oxygen is needed to regenerate NAD⁺. Key steps include the formation of citrate, isomerization, and multiple oxidation events that yield energy carriers essential for cellular respiration.

Overview

Hi. So this video is going to be talking about the citric acid cycle, also known as the Krebs cycle or the TCA cycle. First, I'm going to spend some time just doing an overview of the cycle, and then later we're going to get into the exact nitty gritty of the steps.

The citric acid cycle is a set of various reactions that occur after glycolysis, which generates or creates CO₂ and NADH. Glycolysis is going to create pyruvate. Pyruvate eventually becomes decarboxylated, which you don't necessarily need to know unless you want to in advanced chemistry. But essentially, what it means is it removes the carboxyl group and that creates CO₂, and eventually leads to the creation of Acetyl CoA. Acetyl CoA is the starting molecule for the citric acid cycle. How it is created is through a complex known as the pyruvate dehydrogenase complex, and this is the group of proteins that are responsible for taking pyruvate and turning it into Acetyl CoA so that it can be used for the citric acid cycle.

Once Acetyl CoA is created, the citric acid cycle then uses it and oxidizes it to generate or produce, 1 GTP, 3 NADH, and 1 FADH₂. Out of these three, the NADH is then passed on to the next step of cellular respiration, which is the electron transport chain and used to produce ATP. So, throughout all these, we've been talking about whether or not these cycles require oxygen or use oxygen. The citric acid cycle actually does require oxygen, but it does so indirectly. The citric acid cycle itself doesn't use oxygen, but it's still classified as an aerobic reaction because it needs to have NAD⁺ to run, and oxygen is required for the regeneration of NAD⁺.

This is very similar to some of the other things that we've talked about in previous videos. Here's an overview of the citric acid cycle. You don't need to know any of these words in this video. We'll go over them all in the next one. But you can see here that you start off with Acetyl CoA, it's kind of the circular. And throughout this, oxygen isn't required directly, but it is needed because oxygen replaces NADH⁺, which is then used to create the NADH. So that is the overview of the citric acid cycle. Let's now move on and get into the nitty gritty.

Citric Acid Steps

So now, we are going to get more into the exact steps of the citric acid cycle. This is set up in similar ways to other previous videos, where the important information is here, bolded, and these reactions are just provided to make it easier to understand the text. You don't necessarily need to be able to write out all these reactions; that's for your chemistry class, but the text is going to be important. I am going to point out which steps are most important. The first thing, the first step, is obviously very important because it always comes first, and what happens is, Acetyl CoA is eventually turned into this molecule called citrate, and in the process, CoA is actually released. So, the first step is important because it is the creation of citrate. Then that citrate begins to be used in other steps. The second step is an isomerization step, which just means that atoms are rearranged. The molecule that undergoes isomerization is called hydroxyl. We start with our citrate, then these intermediate products happen, and the hydroxyl group is moved around and isomerized to a different location. You can see here that a water molecule is lost but is eventually added back in. Step 3 is going to be a really important step, and that's going to be carbon dioxide and NADH creation. This happens through carbon oxidation. We start with this molecule called isocitrate, and eventually, NAD⁺ becomes NADH, and CO₂ is released, leaving us with this molecule here. Step 4 is a second step of CO₂ and NADH creation, pretty much the same thing happens as in the second oxidation step, which turns this molecule and creates NADH and CO₂. Another important thing here is that there is this incoming CoA, which gets added here at the end. But remember, the important part isn't these exact chemical reactions, this is just an image of what I'm saying. The important part is CO₂ and NADH creation the second time. Step 5 is going to be the GTP creation. Again, you don't need to know these chemical names, but what happens is GDP comes in, and GTP is released or made, and also the CoA is removed. Here it is, and there it's missing. The 6th step is the FADH₂ creation, so this is going to be a third oxidation step, so keeping track of the steps that involve oxidation. Here we have this molecule; FADH₂ is created, it forms this molecule, and the third oxidation. Then we have a less important step, and that's going to be the addition of water, and the water coming in changes the molecule a little. Then we have step 8, and that's going to be NADH creation. This is the fourth oxidation. So, there are four oxidation events that happen, and each time it creates a new energy molecule of some kind. Here we have NADH. Just to review, I'm going to scroll down. Remember, we started with pyruvate, which came from glycolysis. This pyruvate was turned through the pyruvate dehydrogenase complex into acetyl CoA. Acetyl CoA was then put and turned into citrate, which then circles through the citric acid cycle, and each one of these boxes representing different enzymes plays a role in helping to convert these molecules. You don't necessarily need to know these enzyme names, just know that they exist. And, in that process, we get a lot of things: we get GTP, we get NADH, water is used up, and there are all sorts of things that we get in the citric acid cycle.

Which of the following is not a product of the citric acid cycle?

• A. NADH
• B. CO₂
• C. FADH₂
• D. Acetyle CoA

For each acetyl CoA that is oxidized in the citric acid cycle, what is created?

• A. 1 GTP, 3 NADH, and 1 FAHD₂
• B. 2 GTP, 1 NADH, and 3 FAHD₂
• C. 6 GTP, 2 NADH, and 1 FAHD₂
• D. 1 GTP, 1 NADH, and 1 FAHD₂

The citric acid cycle requires oxygen indirectly, because oxygen is necessary for what to occur?

• A. Replace FADH
• B. Replace GDP
• C. Replace ADP
• D. Replace NAD+

What is the starting molecule for the citric acid cycle?

• A. Glucose
• B. Pyruvate
• C. Acetyl CoA
• D. Citrate

Here’s what students ask on this topic:

What is the citric acid cycle and why is it important?

The citric acid cycle, also known as the Krebs cycle or TCA cycle, is a series of chemical reactions that occur in the mitochondria after glycolysis. It begins with Acetyl CoA and produces energy-rich molecules: 1 GTP, 3 NADH, and 1 FADH₂. These molecules are crucial for the electron transport chain, which generates ATP, the primary energy currency of the cell. Although the cycle does not directly use oxygen, it is classified as aerobic because oxygen is needed to regenerate NAD⁺. This regeneration is essential for the cycle to continue, making it a key component of cellular respiration and energy production.

What are the main steps of the citric acid cycle?

The citric acid cycle involves several key steps: 1) Formation of citrate from Acetyl CoA and oxaloacetate. 2) Isomerization of citrate to isocitrate. 3) Oxidation of isocitrate to α-ketoglutarate, producing NADH and CO₂. 4) Oxidation of α-ketoglutarate to succinyl-CoA, producing NADH and CO₂. 5) Conversion of succinyl-CoA to succinate, generating GTP. 6) Oxidation of succinate to fumarate, producing FADH₂. 7) Hydration of fumarate to malate. 8) Oxidation of malate to oxaloacetate, producing NADH. These steps collectively generate energy carriers essential for cellular respiration.

How does the citric acid cycle contribute to ATP production?

The citric acid cycle contributes to ATP production by generating high-energy molecules: 3 NADH, 1 FADH₂, and 1 GTP per cycle. NADH and FADH₂ are electron carriers that transfer electrons to the electron transport chain (ETC) in the mitochondria. The ETC uses these electrons to create a proton gradient across the mitochondrial membrane, which drives the synthesis of ATP through oxidative phosphorylation. Although the citric acid cycle itself produces only 1 GTP (which can be converted to ATP), the NADH and FADH₂ generated are crucial for the production of a significant amount of ATP in the ETC.

Why is oxygen indirectly required for the citric acid cycle?

Oxygen is indirectly required for the citric acid cycle because it is essential for the regeneration of NAD⁺ from NADH. The cycle produces NADH, which must be oxidized back to NAD⁺ to keep the cycle running. This oxidation occurs in the electron transport chain (ETC), where oxygen acts as the final electron acceptor, forming water. Without oxygen, the ETC cannot function, leading to a shortage of NAD⁺, which halts the citric acid cycle. Therefore, while the cycle itself does not use oxygen directly, it is classified as aerobic due to its dependence on oxygen for NAD⁺ regeneration.

What are the energy-rich molecules produced in the citric acid cycle?

The citric acid cycle produces several energy-rich molecules: 1 GTP, 3 NADH, and 1 FADH₂ per cycle. GTP can be readily converted to ATP, the primary energy currency of the cell. NADH and FADH₂ are electron carriers that transfer high-energy electrons to the electron transport chain (ETC), where they are used to generate a proton gradient that drives ATP synthesis. These molecules are crucial for the production of ATP, making the citric acid cycle a central component of cellular respiration and energy metabolism.