Fatty Acid Oxidation - Video Tutorials & Practice Problems
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Fatty Acid Oxidation 1
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As we've mentioned previously, fats can be used for energy storage and they can be broken down into glycerol and fatty acids and 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 do want to mention that fats can be used for water storage as well as energy. And this comes into play more with creatures that live in desert environments. For example, 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 real quick just to, hearken back to what we talked about in the previous unit, glycerol can be converted into DHAP which will be converted into G3P. And this these are substrates of glycolysis. The, catabolism of glycerol yields one ATP perglycerol 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 previous unit, you know, it produces, more NADH than the reactions can get rid of essentially so it, it's an unsustainable sugar to use in fermentation. Anyhow, moving on to the main stuff. Let's talk about those fatty acids. So, 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 Coase and this reaction is not pictured here but what you all you really need to know about it is they they add a co a 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. Just, you know, it's in his it's in his lecture notes. That's how he thinks of it. So in case it comes up, you know, 2 ATP but that's what the quotes are for. It's really just breaking the 2 acid anhydride bonds. Anyhow, this molecule, this, fatty acyl CoA will be transported into the mitochondrial matrix but it has to first be bound to carnitine. And once it's bound to, it's by the way it's bound to carnitine by carnityl acyltransferase 1. So here is CAT1. This molecule right here is anti porter. And let me get out of the image here. Through this antiporter. And let me get out of the image here. This antiporter, will pass the acylcarnitine into the my, mitochondrial matrix and will move a just plain carnitine out the other way, okay? And once the acylcarnitine gets into the matrix, it's actually going to be broken, back down into acyl CoA and carnitine and that is going to be done by carnitine acyltransferase 2. So, CAT2. This enzyme right here. This is often called the carnitine shuttle and it's because carnitine isn't really consumed in the process. It just kind of shuttles back and forth to move these fatty acids into the matrix where they can undergo beta oxidation. So, beta oxidation as hopefully you figured out at this point occurs in the mitochondrial matrix, right? That's why we're bringing those fatty acids in and beta removes 2 carbon units at a time and it removes them as acetyl CoA. And these are being clipped off again from the fatty acyl CoA that we brought into the mitochondrial matrix. Now, it's basically beta oxidation is basically made up of 4 repeating steps. And as you can see here in this image, well, 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, 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. Actually not sure about. Leave a comment if you know. I'd be curious. Anyways, the co a 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, alright? So, first thing that's going to happen is we are going to oxidize an -ane to an -ene. Okay. We're going to oxidize an -ane to an -ene and it's an acyl CoA dehydrogenase that's going to do this. And it works basically just like succinate dehydrogenase, right? So it's going to, 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, right? So there is the double bond in the molecule. All right. Now we are ready for step 2. Oh and and do take note that that double bond is between carbon 23 on this molecule and it has a trans configuration. These are both both important things to note. You'll see why momentarily. Alright. Step 2, we add water to the ene to form an alcohol. Okay. And that is carried out by, enoyl, CoAhydratase and it's kind of like the conversion from fumarate to maleate. You can see here is our new alcohol group. Alright. Then step 3, we oxidize the alcohol. You can see there it has been oxidized to oops. I'm sorry. I circled the wrong one. There it has been oxidized to the carbonyl. And, this is carried out by a beta hydro excuse me. Beta hydroxy acyl CoA dehydrogenase. Oh, that's a mouthful. And that's going to take NAD plus and convert it into NADH. And this is like malate dehydrogenase. Okay. 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. Okay. These are important parallels to bear in mind. They can come up on test questions sometimes. Okay. So last thing that's going to happen, step 4 is thiolase is going to cleave off, the acetyl acetyl CoA and add a CoA to the new end of the fatty acid. And you can see that here is our acetyl CoA. Here it's come off. The 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, this gets broken and you get left with 2 acetyl CoAs, right? Because in this last step, we add a CoA to the new end. Well, guess what? The new end is only 2 carbon 2 carbon molecule and you add that coA on, you're left with Acetyl CoA. So basically with beta oxidation, like let's say you have a a ten a 10 carbon, fatty acid chain. 10 carbon chain, it's going to go through 5 rounds. I'm carbons. Our 52 carbon units, right? Each of these are 2 carbons. So you're going to have 1 round, 2 rounds, 3 rounds and then the last round right there, right? You're not going to do another round there. So if it's, so the, you know, kind of like little trick, the rule to remember it's sort of like half the number of, carbons minus 1 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, right? Remember, this we're kind of talking about perfect scenario. What if we have a uneven fatty acid chain? Chain. A fatty acid chain that has an uneven number of carbon or I'm sorry, an odd number of carbons. What are we going to do then? Well, let's flip the page and find out.
2
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Fatty Acid Oxidation 2
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8m
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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 confirmations 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 23, carbon on the molecule. Now, with what we're about to talk about, I just wanna say that don't obsess over the details. Just try to come away with sort of like the an understanding of the generalities. So, you know, let's take a look at this figure here. Basically we're, you know, doing beta oxidation, chipping away at this until Boom. We get right up close and personal with those double bonds. Now, those both those double bonds are, in the cis form. So both of them are unacceptable. Additionally, we want this double bond to be between the 23 carbon. Right now, it's between 34. So, we're going to use an isomerase, 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 FADH 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 plus. 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, it 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 acid, 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 acid, that last step is going to have a 5 carbon molecule, and we're gonna chop it into an acetyl co a, 2 carbons, and a propanoyl CoA, just 3 carbons. Now, acetyl CoA, that's fine. We can work with that. Right? But 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 a 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 good exercise for sort of 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 going to happen. Now if 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 minuteus 1. So 7 rounds. And this is going to produce 7 acetyl Coase. Alright. So from beta oxidation alone, we're going to generate 7 FADHs 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 CoA's. Sorry. Seven rounds of beta oxidation, 8 Acetyl Coase. My bad, guys. My bad. Sorry if you caught that. Anyways, one acetyl co a going through the citric acid cycle yields 1 FADH 2 and 3 NADH as well as one ATP or GTP. So 8 acetyl CoA is going to make 8 FADH, 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 like, 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.
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