Overview of Fatty Acid Synthesis Process

Hey everyone, in this lesson we're talking about fatty acid synthesis. We're going to get into where fatty acid synthesis occurs in the body, what is required, how it actually happens, and then we're going to get into what regulates fatty acid synthesis. So to begin, what is a fatty acid? Well, a fatty acid, as you can see here, is a chemical structure of a fatty acid. A fatty acid contains a carboxylic acid chemical group, as well as a chain of hydrocarbons. Now because of this, it's considered amphiphilic, which means that a fatty acid has properties of both being hydrophilic and hydrophobic. Now the hydrocarbon chain is the hydrophobic portion of the fatty acid, and with increasing length of a hydrocarbon chain, it becomes more hydrophobic. So at some point when the chain is so long, we just consider the fatty acid completely hydrophobic. Synthesis of fatty acids requires a few different things. One is that it requires high levels of acetyl-CoA in the cytoplasm, and we'll get into why that's important in a bit. It also requires high levels of NADPH, which is normally derived from the pentose phosphate pathway. Fatty acid synthesis occurs in the cytosol as opposed to beta oxidation or fatty acid catabolism, which occurs in the mitochondria. Now, fatty acids can be used for a variety of different purposes. When fatty acids are used as energy storage molecules, they're actually stored as tricylglycerols or triglycerides, which are just three fatty acid chains attached to a glycerol backbone. And triglycerides are typically... stored in the adipose tissue. Fat acids and triglycerides are anhydrous, which means that they can store a higher amount of energy per mass, unlike glycogen. Fat acid synthesis occurs in two primary locations in the body, in one in the liver, the other in adipose tissue. Now, as I mentioned before, this all is occurring in the cytosol. And because of that, we require acetyl-CoA in the cytosol. And acetyl-CoA... is typically in the mitochondria, it cannot leave the mitochondrial matrix, which means that it has to be brought out in a different form. And that form is citrate. Citrate is actually transported out of the mitochondria, and it can be acted on by the enzyme ATP citrate lyase, releasing an oxaloacetate and forming acetyl-CoA. This is how we get our cytosolic supply of acetyl-CoA. Now, along with acetyl-CoA, we require a vitamin B7 derivative carboxybiotin. Now, these two will actually undergo an enzymatic reaction with the enzyme acetyl-CoA carboxylase. Now, the purpose of the carboxybiotin is actually to donate a carboxyl group to the acetyl-CoA. This reaction requires one ATP, and it forms malonyl-CoA. In the process, carboxybiotin is actually recycled into biotin, and biotin can actually be recycled back into carboxybiotin for later reactions. And the acetyl-CoA carboxylase step to form melanocoy is actually the committed step of fatty acid synthesis, and it is also the rate-limiting step of fatty acid synthesis, so it is a very important step. And because it is very important, it is highly regulated. ACC is actually inhibited by glucagon. inhibited by epinephrine, palmitoyl-CoA, and also by AMPK through phosphorylation. Now, acetyl-CoA carboxylase is activated by a few different things as well. One of those is insulin. Insulin actually activates acetyl-CoA carboxylase. Citrate also activates acetyl-CoA carboxylase, which makes sense. Citrate in the cytosol would represent a precursor of acetyl-CoA and also signals to the cell that energy supplies high in the cell, so it can be stored in the fat. And another regulator, or another upregulator of acetyl-CoA carboxylase is carbohydrate response element binding protein, or CHREBP. Now, this is actually a transcription factor that actually upregulates this enzyme, and this transcription factor is itself upregulated. by a couple things. One is that it's upregulated by high carbohydrate or caloric intake, but it is actually negatively inhibited by fasting. So there is a nutrient regulation on this transcription factor, which will actually regulate acetyl-CoA carboxylase. Now, once we have malonyl-CoA, malonyl-CoA is actually a potent negative antidepressant. regulator of fatty acid catabolism. And it does this by inhibiting CPT-1. We'll get into that in the fatty acid catabolism lesson. So just remember that malonyl-CoA is a potent negative regulator of fatty acid catabolism. Now once we have malonyl-CoA, malonyl-CoA can actually be recycled itself by the enzyme malonyl-CoA decarboxylase into acetyl-CoA and carbon dioxide. So malonyl-CoA decarboxylase can actually take malonyl-CoA and recycle the malonyl-CoA back to acetyl-CoA and carbon dioxide. Fatty acid synthesis occurs on a giant protein complex known as fatty acid synthase. Now, fatty acid synthase is about 250 to 270 kilodaltons in weight, so it is very large. Now, it actually is composed of several different moieties. One is an acyl carrier protein, or ACP, which itself has a vitamin B5-derived component we call phosphopantothione. Now, another important binding point on this is acyl. protein complex of fatty acid synthase is through a cysteine residue, and we'll get into how that occurs as well. So once we have acetyl-CoA and malonyl-CoA from an acetyl-CoA carboxylase reaction, we can go through one cycle of the fatty acid synthase protein complex, and now I'll show you how that happens. So the first thing that'll happen is acetyl-CoA will actually bind to a sulfhydryl group on the phosphopantothene moiety on the acyl carrier protein of the fatty acid synthase protein complex. Now in doing so, it has removed the coenzyme A from the acetyl-CoA, and after that, after it's bound to phosphopantothene, it'll actually shift the acetyl group to the other sulfhydryl group on fatty acid synthase. Now once it's done that, malonyl-CoA will actually bind itself. to that sulfhydryl group on the phosphopantothene moiety on the fatty acid synthase. So once these two have been bound to the fatty acid synthase protein complex, what will happen is that the acetyl group from the acetyl-CoA will actually undergo an enzymatic reaction and will actually take two carbons from the malonyl-CoA to form butyryl-CoA. And in doing so, it'll release the leftover carbon from the malonyl-CoA as a carbon dioxide. So what you have to remember is that the synthesis of a fatty acid chain starts with an acetyl-CoA and the malonyl-CoA acts as a two-carbon donor. It donates two carbons to the acetyl-CoA and the third carbon from malonyl-CoA is released as a carbon dioxide in the formation of butyryl-CoA. So once we have butyryl-CoA, it is a four carbon molecule. And all reactions in extending the fatty acid chain occur on the fatty acid synthase protein complex. So the next step is the same as this step before. It actually takes another malonyl-CoA, which is again used as a two carbon donor, and will actually get added, the two carbons will be added from the malonyl-CoA to the butyryl-CoA in a condensation reaction. I have an R group here. This is just the extending of the carbon chain. We have a ketone chemical group added to this growing carbon chain. Then it undergoes a reduction reaction using NADPH. That's why we need NADPH in fatty acid synthesis. It reduces the ketone to a hydroxyl group. Then we undergo a dehydration reaction. We actually remove that hydroxyl group. And then we go through another reduction reaction with another NADPH to form our six-carbon molecule now. So we've gone from butyryl-CoA, which is a form of carbon molecule. We take two carbons from malonyl-CoA, and we end up after one cycle of the fatty acid synthase enzyme, we get another molecule, but now it has six carbons. And this just keeps going. So we go through another cycle. We use another malonyl-CoA as a two-carbon donor, go through condensation reaction, go through another reduction reaction, dehydration reaction, reduction reaction, all again extending the acyl chain by two carbons each cycle. So when does this stop? Well, it actually stops when we get to the final product, which is palmitate, or a 16-carbon chain. So the total amount of cycles is actually seven because... Two carbons come from malonyl-CoA each cycle. Times seven, there's 14. We started with acetyl-CoA, so it comes to 16. So the summary of the fatty acid. synthesis and the fatty acid synthase cycle leads us to an end product of palmitate which is 16 carbon saturated fatty acid zero means there's no double bonds there are a total of seven cycles in the fatty acid synthase reactions or the fatty acid synthesis cycle there's actually seven cycles because again we start with two carbon acetyl-CoA And malonyl-CoA acts as a two-carbon donor each cycle, which means we use seven malonyl-CoAs. So that's 14 carbons plus the two carbons from the acetyl-CoA leads us to palmitate. And each cycle actually uses two NADPH. There's actually two reduction reactions in each cycle that leads us to using 14 NADPH. And there's actually seven ATP utilized. Now, where's the ATP, you might say? Well, the ATP is actually used in the acetyl-CoA carboxylase reaction. So we need seven malonyl-CoA to actually go through seven cycles. Each malonyl-CoA costs one ATP. So that's where we're getting seven ATP. There's seven carbon dioxide is produced. Each time we add one malonyl-CoA, one carbon dioxide is released. And the total equation for the reaction is as follows. Eight acetyl-CoA are utilized. We have one acetyl-CoA for the beginning, and seven acetyl-CoA are used to make the seven malonyl-CoAs. We need 14 NADPH, 7 ATP, 14 hydrogen ions, and we produce a palmitic acid, and the rest of it is just the recycled components of the reaction. Anyways guys, I hope you found this video helpful. If you did, please like and subscribe for more videos like this one. And as always, thank you so much for watching and have a great day.

Well, a fatty acid, as you can see here, is a chemical structure of a fatty acid. A fatty acid contains a carboxylic acid chemical group, as well as a chain of hydrocarbons. Now because of this, it's considered amphiphilic, which means that a fatty acid has properties of both being hydrophilic and hydrophobic.

Now the hydrocarbon chain is the hydrophobic portion of the fatty acid, and with increasing length of a hydrocarbon chain, it becomes more hydrophobic. So at some point when the chain is so long, we just consider the fatty acid completely hydrophobic. Synthesis of fatty acids requires a few different things.

One is that it requires high levels of acetyl-CoA in the cytoplasm, and we'll get into why that's important in a bit. It also requires high levels of NADPH, which is normally derived from the pentose phosphate pathway. Fatty acid synthesis occurs in the cytosol as opposed to beta oxidation or fatty acid catabolism, which occurs in the mitochondria.

Now, fatty acids can be used for a variety of different purposes. When fatty acids are used as energy storage molecules, they're actually stored as tricylglycerols or triglycerides, which are just three fatty acid chains attached to a glycerol backbone. And triglycerides are typically...

stored in the adipose tissue. Fat acids and triglycerides are anhydrous, which means that they can store a higher amount of energy per mass, unlike glycogen. Fat acid synthesis occurs in two primary locations in the body, in one in the liver, the other in adipose tissue. Now, as I mentioned before, this all is occurring in the cytosol. And because of that, we require acetyl-CoA in the cytosol.

And acetyl-CoA... is typically in the mitochondria, it cannot leave the mitochondrial matrix, which means that it has to be brought out in a different form. And that form is citrate.

Citrate is actually transported out of the mitochondria, and it can be acted on by the enzyme ATP citrate lyase, releasing an oxaloacetate and forming acetyl-CoA. This is how we get our cytosolic supply of acetyl-CoA. Now, along with acetyl-CoA, we require a vitamin B7 derivative carboxybiotin.

Now, these two will actually undergo an enzymatic reaction with the enzyme acetyl-CoA carboxylase. Now, the purpose of the carboxybiotin is actually to donate a carboxyl group to the acetyl-CoA. This reaction requires one ATP, and it forms malonyl-CoA.

In the process, carboxybiotin is actually recycled into biotin, and biotin can actually be recycled back into carboxybiotin for later reactions. And the acetyl-CoA carboxylase step to form melanocoy is actually the committed step of fatty acid synthesis, and it is also the rate-limiting step of fatty acid synthesis, so it is a very important step. And because it is very important, it is highly regulated.

ACC is actually inhibited by glucagon. inhibited by epinephrine, palmitoyl-CoA, and also by AMPK through phosphorylation. Now, acetyl-CoA carboxylase is activated by a few different things as well. One of those is insulin.

Insulin actually activates acetyl-CoA carboxylase. Citrate also activates acetyl-CoA carboxylase, which makes sense. Citrate in the cytosol would represent a precursor of acetyl-CoA and also signals to the cell that energy supplies high in the cell, so it can be stored in the fat.

And another regulator, or another upregulator of acetyl-CoA carboxylase is carbohydrate response element binding protein, or CHREBP. Now, this is actually a transcription factor that actually upregulates this enzyme, and this transcription factor is itself upregulated. by a couple things. One is that it's upregulated by high carbohydrate or caloric intake, but it is actually negatively inhibited by fasting. So there is a nutrient regulation on this transcription factor, which will actually regulate acetyl-CoA carboxylase.

Now, once we have malonyl-CoA, malonyl-CoA is actually a potent negative antidepressant. regulator of fatty acid catabolism. And it does this by inhibiting CPT-1. We'll get into that in the fatty acid catabolism lesson. So just remember that malonyl-CoA is a potent negative regulator of fatty acid catabolism.

Now once we have malonyl-CoA, malonyl-CoA can actually be recycled itself by the enzyme malonyl-CoA decarboxylase into acetyl-CoA and carbon dioxide. So malonyl-CoA decarboxylase can actually take malonyl-CoA and recycle the malonyl-CoA back to acetyl-CoA and carbon dioxide. Fatty acid synthesis occurs on a giant protein complex known as fatty acid synthase. Now, fatty acid synthase is about 250 to 270 kilodaltons in weight, so it is very large.

Now, it actually is composed of several different moieties. One is an acyl carrier protein, or ACP, which itself has a vitamin B5-derived component we call phosphopantothione. Now, another important binding point on this is acyl.

protein complex of fatty acid synthase is through a cysteine residue, and we'll get into how that occurs as well. So once we have acetyl-CoA and malonyl-CoA from an acetyl-CoA carboxylase reaction, we can go through one cycle of the fatty acid synthase protein complex, and now I'll show you how that happens. So the first thing that'll happen is acetyl-CoA will actually bind to a sulfhydryl group on the phosphopantothene moiety on the acyl carrier protein of the fatty acid synthase protein complex.

Now in doing so, it has removed the coenzyme A from the acetyl-CoA, and after that, after it's bound to phosphopantothene, it'll actually shift the acetyl group to the other sulfhydryl group on fatty acid synthase. Now once it's done that, malonyl-CoA will actually bind itself. to that sulfhydryl group on the phosphopantothene moiety on the fatty acid synthase.

So once these two have been bound to the fatty acid synthase protein complex, what will happen is that the acetyl group from the acetyl-CoA will actually undergo an enzymatic reaction and will actually take two carbons from the malonyl-CoA to form butyryl-CoA. And in doing so, it'll release the leftover carbon from the malonyl-CoA as a carbon dioxide. So what you have to remember is that the synthesis of a fatty acid chain starts with an acetyl-CoA and the malonyl-CoA acts as a two-carbon donor. It donates two carbons to the acetyl-CoA and the third carbon from malonyl-CoA is released as a carbon dioxide in the formation of butyryl-CoA.

So once we have butyryl-CoA, it is a four carbon molecule. And all reactions in extending the fatty acid chain occur on the fatty acid synthase protein complex. So the next step is the same as this step before.

It actually takes another malonyl-CoA, which is again used as a two carbon donor, and will actually get added, the two carbons will be added from the malonyl-CoA to the butyryl-CoA in a condensation reaction. I have an R group here. This is just the extending of the carbon chain.

We have a ketone chemical group added to this growing carbon chain. Then it undergoes a reduction reaction using NADPH. That's why we need NADPH in fatty acid synthesis. It reduces the ketone to a hydroxyl group. Then we undergo a dehydration reaction.

We actually remove that hydroxyl group. And then we go through another reduction reaction with another NADPH to form our six-carbon molecule now. So we've gone from butyryl-CoA, which is a form of carbon molecule.

We take two carbons from malonyl-CoA, and we end up after one cycle of the fatty acid synthase enzyme, we get another molecule, but now it has six carbons. And this just keeps going. So we go through another cycle.

We use another malonyl-CoA as a two-carbon donor, go through condensation reaction, go through another reduction reaction, dehydration reaction, reduction reaction, all again extending the acyl chain by two carbons each cycle. So when does this stop? Well, it actually stops when we get to the final product, which is palmitate, or a 16-carbon chain. So the total amount of cycles is actually seven because... Two carbons come from malonyl-CoA each cycle.

Times seven, there's 14. We started with acetyl-CoA, so it comes to 16. So the summary of the fatty acid. synthesis and the fatty acid synthase cycle leads us to an end product of palmitate which is 16 carbon saturated fatty acid zero means there's no double bonds there are a total of seven cycles in the fatty acid synthase reactions or the fatty acid synthesis cycle there's actually seven cycles because again we start with two carbon acetyl-CoA And malonyl-CoA acts as a two-carbon donor each cycle, which means we use seven malonyl-CoAs. So that's 14 carbons plus the two carbons from the acetyl-CoA leads us to palmitate. And each cycle actually uses two NADPH. There's actually two reduction reactions in each cycle that leads us to using 14 NADPH.

And there's actually seven ATP utilized. Now, where's the ATP, you might say? Well, the ATP is actually used in the acetyl-CoA carboxylase reaction.

So we need seven malonyl-CoA to actually go through seven cycles. Each malonyl-CoA costs one ATP. So that's where we're getting seven ATP.

There's seven carbon dioxide is produced. Each time we add one malonyl-CoA, one carbon dioxide is released. And the total equation for the reaction is as follows.

Eight acetyl-CoA are utilized. We have one acetyl-CoA for the beginning, and seven acetyl-CoA are used to make the seven malonyl-CoAs. We need 14 NADPH, 7 ATP, 14 hydrogen ions, and we produce a palmitic acid, and the rest of it is just the recycled components of the reaction. Anyways guys, I hope you found this video helpful.

If you did, please like and subscribe for more videos like this one. And as always, thank you so much for watching and have a great day.

Transcript for:Overview of Fatty Acid Synthesis Process

Transcript for:
Overview of Fatty Acid Synthesis Process