Fatty Acid Oxidation - Online Tutor, Practice Problems & Exam Prep

Fats serve as energy storage, breaking down into glycerol and fatty acids, which convert to Acetyl CoA via beta oxidation. Fatty acids must first be activated to fatty acyl CoA and transported into mitochondria using carnitine. Beta oxidation involves four steps: oxidation, hydration, further oxidation, and thiolysis, producing Acetyl CoA. Unsaturated fatty acids may require isomerization for proper oxidation. Odd-chain fatty acids yield Acetyl CoA and propanoyl CoA, which is converted to succinyl CoA for the citric acid cycle, generating significant ATP through these metabolic pathways.

Fatty Acid Oxidation 1

As we've mentioned previously, fats can be used for energy storage and they can be broken down into glycerol and fatty acids. Fatty acids can be converted into Acetyl CoA through beta oxidation. We're going to cover that process now, but before we get there, we need to talk about how fatty acids actually get into mitochondria. Before I get ahead of myself, though, I also want to mention that fats can be used for water storage as well as energy. This comes into play more with creatures that live in desert environments, such as camels. Most people incorrectly think that camels' humps are filled with water. They're filled with fat that the camels can convert into water.

Anyhow, before we get to the fatty acids, just to harken back to what we talked about in the previous unit, glycerol can be converted into DHAP, which will be converted into G3P. These are substrates of glycolysis. The catabolism of glycerol yields one ATP per glycerol molecule and 2 NADHs, which is great if you're trying to do respiration, but that's a lot of NADH to be produced, so it makes it a non-fermentable sugar. Basically, if you recall from the previous unit, it produces more NADH than the reactions can get rid of, making it an unsustainable sugar to use in fermentation. Anyhow, moving on to the main topics.

Let's talk about those fatty acids. They undergo beta oxidation to enter the citric acid cycle as Acetyl CoA or, in some cases, succinyl CoA. We'll get to that later. Fatty acids have to first be activated by being converted into fatty acyl CoA. This reaction is not pictured here, but what you really need to know about it is that they add a CoA onto the molecule and it costs 2 ATP, sort of. I have that in quotes. Basically, it costs 1 ATP, and then you break both anhydride bonds. So, your professor likes to think of it as costing 2 ATP. That's how he thinks of it in his lecture notes. So, in case it comes up, that's what the quotes are for. It's really just breaking the two acid anhydride bonds.

This molecule, fatty acyl CoA, will be transported into the mitochondrial matrix but it has to first be bound to carnitine. And once it's bound, it's by the way bound to carnitine by carnitine acyltransferase 1. So here is CAT1. This molecule right here is an antiporter. This antiporter will pass the acylcarnitine into the mitochondrial matrix and will move plain carnitine out the other way. Once the acylcarnitine gets into the matrix, it's going to be broken back down into acyl CoA and carnitine. This is going to be done by carnitine acyltransferase 2, or CAT2. This enzyme is often called the carnitine shuttle because carnitine isn't really consumed in the process. It just shuttles back and forth to move these fatty acids into the matrix where they can undergo beta oxidation.

Beta oxidation, as you've hopefully figured out at this point, occurs in the mitochondrial matrix. That's why we're bringing those fatty acids in. Beta oxidation removes 2-carbon units at a time as acetyl CoA. These are being clipped off again from the fatty acyl CoA that we brought into the mitochondrial matrix. Now, beta oxidation is basically made up of 4 repeating steps. As you can see here in this image, first of all, these names are not in English but that's fine. You don't need to worry about these names. You don't really need to worry about the enzymes involved, you know, memorizing all the specific reactions they do. So what you should know is the basic things that are happening in each of these four steps. So first, what's going on right here, this is our fatty acid. Let me actually scroll down a little so you can see this better. So here we have our fatty acid. Here's our CoA. That's at least the same in whatever language this is. Not sure about. Leave a comment if you know.

Anyhow, the CoA and the fatty acid are combined into that fatty acyl CoA right here. This is our fatty acyl CoA, and that is the activation step. Now, we have beta oxidation. The first thing that's going to happen is we are going to oxidize an -ane to an -ene. It's an acyl CoA dehydrogenase that's going to do this. It works basically just like succinate dehydrogenase. It's going to take FAD and reduce it to FADH₂ in the process, and you can see really what it's doing is it's introducing a double bond right here. Now we're ready for step 2. Oh, and do take note that the double bond is between carbon 2-3 on this molecule and it has a trans configuration. These are both important things to note. You'll see why momentarily. Step 2, we add water to the ene to form an alcohol. And that is carried out by enoyl-CoAhydratase, and it's kind of like the conversion from fumarate to malate. You can see here is our new alcohol group. Then step 3, we oxidize the alcohol. You can see there it has been oxidized to the carbonyl. This is carried out by a beta-hydroxyacyl-CoA dehydrogenase.

And that's going to take NAD⁺ and convert it into NADH. And this is like malate dehydrogenase. So notice that there are these parallels between these particular steps we're seeing here and reactions that we see in the citric acid cycle. These are important parallels to bear in mind. They can come up on test questions sometimes. So the last thing that's going to happen, step 4, is thiolase is going to cleave off the acetyl-CoA and add a CoA to the new end of the fatty acid. And you can see that here is our acetyl CoA. It's come off. You continue through step 1 and keep repeating the cycle until we are left with this molecule. And guess what happens when this molecule goes through step 4? Well, it gets broken and you get left with 2 acetyl CoAs because in this last step, we add a CoA to the new end. Well, guess what? The new end is only a 2-carbon molecule, and you add that CoA on, you're left with acetyl CoA. So basically, with beta oxidation, let's say you have a 10-carbon fatty acid chain. It's going to go through 5 rounds. Each round removes 2 carbon units. The rule to remember, it's sort of like half the number of carbons minus one basically. Anyhow, let's turn the page and talk about when things don't work out as cleanly for beta oxidation as they did here. Remember, this, we're kind of talking about a perfect scenario. What if we have an uneven fatty acid chain? A fatty acid chain that has an odd number of carbons. What are we going to do then? Well, let's flip the page and find out.

Fatty Acid Oxidation 2

Unsaturated fatty acids sometimes require a little helping hand with beta oxidation, and that is because they sometimes need to move that ene around, right? So, remember trans conformations are okay, but cis have to be rearranged. Furthermore, we're going to want that double bond like we saw before. We're going to want it between the 2 and 3 carbon on the molecule. Now, with what we're about to talk about, I just want to say that don't obsess over the details. Just try to come away with an understanding of the generalities. So, you know, let's take a look at this figure here. Basically, we're doing beta oxidation, chipping away at this until boom. We get right up close and personal with those double bonds. Now, both of those double bonds are in the cis form. So both of them are unacceptable. Additionally, we want this double bond to be between the 2 and 3 carbon. Right now, it's between 3 and 4. So, we're going to use an isomerase to actually move that over into the right position and then from there, we can just do normal beta oxidation, right? Chop it off. Here is the catch. The catch is if you do this, you're not going to generate an FADH₂ from that round of beta oxidation, right? Because the first step of beta oxidation is introducing that double bond and reducing FAD, right? Well, you didn't introduce that double bond. You just moved it over. So you're not going to make an FAD if you do that. Alright. Just something to be aware of and keep track of if you're thinking about the beta oxidation of various molecules. Alright. So, moving on. If you have multiple points of unsaturation in a particular arrangement, it might actually prevent an isomerase from being able to take care of the issue, right? So right here, that can't be dealt with by an isomerase alone. So what's going to have to happen is we're going to have to use NADPH to reduce our ene and then we can deal with it. So we're going to have NADPH come in and NADPH is just like NADH. It's an electron carrier. It's going to drop off its electrons to reduce that bond and we're going to be left with NADP⁺. And then, we'll go through, or depending on the confirmation here, we can actually just move this bond over, right, and do beta oxidation. In some situations, you might not have an arrangement like that and you might reduce with NADPH and then actually have to create the double bond and generate an FADH₂. So odd-numbered fats, odd-numbered fatty acids will end up with, well, if we have an even number of fatty acids, right, in our last round of beta oxidation, we're gonna have a 4 carbon molecule that's gonna get chopped into 2 acetyl CoAs, right? Both of those 2 carbon molecules. If we have an odd number of fatty acids, that last step is going to have a 5 carbon molecule, and we're gonna chop it into an acetyl CoA, 2 carbons, and a propanoyl CoA, just 3 carbons. Now, acetyl CoA, that's fine. We can work with that. Right? But propanoyl CoA, we're going to have to modify that molecule before we can do anything with it. And what we're going to do is we're going to add CO₂ to it. It's actually going to cost ATP. And we're going to convert it into succinyl CoA. Hey, I remember that molecule. That's used in step 5 of the tricarboxylic acid cycle or the citric acid cycle. I abbreviated citric acid cycle here as TCA. But that's just the citric acid cycle. There's actually 3 well, there, wait. Let's get messy. There's actually three names for the citric acid cycle. You have the citric acid cycle, the Krebs cycle, and the tricarboxylic acid cycle. Same thing. TCA is often the abbreviation for this cycle though. Anyhow, moving on. Last thing we're going to do is we're going to take a look at this molecule, acid, and we are going to put it through beta oxidation and see how much ATP we generate. This is going to be a good exercise for tracing the logic of the various metabolic pathways we've been talking about. So I'm going to hop out of the image here, free up some space, so you can see the molecule, and here we go. So palmitic acid, happen. Now if you're going to happen. Now if you remember before there's like a little simple rule you can think of to figure out how many acetyl CoA you're going to produce, right, and how many rounds of beta oxidation you're going to go through and that little trick is you do half the number of carbons in the molecule minus 1, right? So here we have 16 carbons divided by 2. That's 8 minus 1. So 7 rounds. And this is going to produce 7 acetyl CoAs. Alright. So from beta oxidation alone, we're going to generate 7 FADH₂s which will lead to 10.5 ATPs. And we're going to generate 7 NADHs which will lead to 17.5 ATPs. Now, these 7 acetyl CoAs are going to go through the citric acid cycle, right? When I'm sorry. Whoops. This is 8 acetyl CoAs. Sorry. Seven rounds of beta oxidation, 8 Acetyl CoAs. My bad, guys. My bad. Sorry if you caught that. Anyways, one acetyl CoA going through the citric acid cycle yields 1 FADH₂ and 3 NADH as well as one ATP or GTP. So 8 acetyl CoAs are going to make 8 FADH₂s, right, which is 12 ATP. NADH, that's going to make 24 of those guys, right, which is going to lead to let's see, 60 ATP. And don't forget that we're also going to be producing 8 ATP or GTP. Same thing. We're going to count them, right, from the citric acid cycle. So total, we are going to make how much ATP? 108 ATP by putting palmitic acid through beta oxidation. That's a ton of ATP, right? Pretty crazy. If you're wondering, you know, just if you're wondering like, hey, wait, that's so much energy. Why do we use glucose and not just use fat all the time? The answer is actually if you divide by the molecular weight, there's more energy per weight in glucose than there is in fatty acids. Even though one fatty acid can generate, you know, a ton of ATP. Alright. That's all I have for this exam review. Let's move on to some exam practice questions.

Here’s what students ask on this topic:

What is the process of beta oxidation in fatty acid metabolism?

Beta oxidation is a metabolic process where fatty acids are broken down in the mitochondrial matrix to generate Acetyl CoA, which enters the citric acid cycle. The process involves four main steps: oxidation, hydration, further oxidation, and thiolysis. Initially, fatty acids are activated to fatty acyl CoA and transported into the mitochondria using carnitine. During beta oxidation, two-carbon units are removed from the fatty acyl CoA as Acetyl CoA. This process repeats until the entire fatty acid is converted into Acetyl CoA, producing significant amounts of ATP through subsequent metabolic pathways.

How are fatty acids transported into the mitochondria for beta oxidation?

Fatty acids are transported into the mitochondria through a process involving carnitine. First, fatty acids are activated to form fatty acyl CoA, which is then bound to carnitine by the enzyme carnitine acyltransferase 1 (CAT1). This complex is transported into the mitochondrial matrix via an antiporter mechanism, where acylcarnitine is exchanged for free carnitine. Once inside, carnitine acyltransferase 2 (CAT2) converts acylcarnitine back to fatty acyl CoA, releasing carnitine to be reused. This transport mechanism is often referred to as the carnitine shuttle.

What happens to odd-chain fatty acids during beta oxidation?

Odd-chain fatty acids undergo beta oxidation similarly to even-chain fatty acids but yield a different final product. The last cycle of beta oxidation for odd-chain fatty acids produces one Acetyl CoA (2 carbons) and one propanoyl CoA (3 carbons). Propanoyl CoA cannot directly enter the citric acid cycle and must be converted to succinyl CoA. This conversion involves adding a CO₂ molecule, a process that requires ATP. Succinyl CoA then enters the citric acid cycle, allowing the complete oxidation of the odd-chain fatty acid.

How do unsaturated fatty acids undergo beta oxidation?

Unsaturated fatty acids require additional steps for beta oxidation due to the presence of double bonds. If the double bond is in the cis configuration or not in the correct position, enzymes like isomerases and reductases are needed. Isomerases move the double bond to the correct position, while reductases use NADPH to reduce the double bond if necessary. These adjustments ensure that the fatty acid can proceed through the standard beta oxidation pathway. However, these modifications may result in the loss of FADH₂ production in certain steps.

Why is beta oxidation important for energy production?

Beta oxidation is crucial for energy production because it breaks down fatty acids into Acetyl CoA, which enters the citric acid cycle to produce ATP. Fatty acids are a dense energy source, and their oxidation generates significant amounts of ATP. For example, the oxidation of palmitic acid (a 16-carbon fatty acid) produces 108 ATP molecules. This high energy yield is essential for sustaining prolonged activities and maintaining metabolic functions, especially when glucose levels are low.