Fatty Acid Synthesis

so now let's actually take a look at the individual steps that help us generate fatty acid molecules now as we look at all these different steps keep in mind that all of them take place in the cytoplasm of our cell now let's briefly recall what happened in the previous several lectures so we said that the building blocks of fatty acid molecules are acetyl coenzyme a molecules and we build these acetyl coenzyme a molecules in a matrix of the mitochondria so to actually use acetyl coenzyme a to synthesize fatty acid molecules we have the transport those acetyl coenzyme a molecules from the matrix of the mitochondria and to the cytoplasm of that cell so let's assume that actually took place so we have the CTA coenzyme a molecule and it's found in the cytoplasm of that cell what happens next well if the conditions are right for fatty acid synthesis that is if we have high levels of citrate and high levels of ATP then that will promote the process of fatty acid synthesis and what that means is we're going to commit the cetyl coenzyme a molecule to actually undergoing fatty acid synthesis and this is the step that commits the acetyl coenzyme a to helping form that fatty acid chain so let's see what this step actually consists of so firstly this the enzyme that catalyzes this step is a carboxylase more specifically it's acetyl coenzyme a carboxylase and just like any other carboxylase this carboxylase requires three different things number one is it means an energy source and that's where ATP comes into play number two is it means a carbon source why well because as this name implies the carboxylase will actually attach a carbon dioxide onto the cetyl coenzyme a molecule elongating this molecule by one carbon and that's why we have the bicarbonate number three is attached covalently onto the carboxylase is biotin and biotin is a vitamin b7 molecule now the reaction as shown on the board is actually the sum of two individual reaction so this is actually the overall net reaction of the sum of two different reactions that are not shown on the board but I'd like to talk about them for just a moment because they actually demonstrate the importance of biotin so what happens in step number one in this reaction so in step number one we have the hydrolysis of ATP by this carboxylase and the energy that is released in the hydrolysis of ATP helps us attach a carbon dioxide onto the biotin so in step number one we form and that's notch on the board but we form a complex that consists of carbon dioxide attached onto biotin which is also attached onto the carboxylase now in the second step that's that once again is not shown that carbon dioxide is transferred from the biotin onto the CTL coenzyme a molecule and we generate malonyl coenzyme a so that's the importance of biotin biotin allows the binding of that carbon dioxide which ultimately transfers that carbon dioxide onto the CTL coenzyme a to form this malonyl coenzyme a now this step is very important for three reasons number one is it commits this e to coenzyme a molecule number two is it's the rate limiting step and number three is this is the enzyme that is regulated to basically either inhibit or activate fatty acid synthesis now we're not going to focus on the regulation this enzyme because that's actually pretty complicated so we'll save that discussion for a later lecture so remember three things about this step number one is it commits the molecule number two is it's a regulatory step number three is it's a rate limiting step and we'll come back to this step when we'll look at step number four now once we form the malonyl coenzyme a molecule let's put aside for a moment and let's look at step number one now the enzyme that catalog is steps one through step seven is fatty acids in things I remember that fatty acid synthase or simply FAS is a single polypeptide chain that actually contains seven different catalytic sites seven different catalytic domains as well as an A and an ACP an ACP domain and the ACP domain stands for acyl carrier protein remember the acyl carrier protein actually contains a phosphatase a thymine group and that group contains this self hydral self hydro group and that will allow the binding of certain molecules as we'll see in just a moment so this is AD this is our FAC FAS and we have this acp that contains the phosphatase a þÿÿÿ that is not shown that contains this self Hyjal group and that will bind this molecule the acetyl coenzyme a as we'll see in just a moment in addition you also have to be aware of this cysteine residue that is also present in this FAS molecule because it will also play an appropriate C in just a moment so step number one is catalyzed by one of the catalytic domains we call acetyl translate and that is found on this FAS molecule and so what this enzyme does or what this catalytic domain does is it catalyzed the attachment of this acetyl coenzyme a molecule onto this sulfhydryl group and we generate this intermediate shown here in addition we kick off the coenzyme a as shown here now this acetyl coenzyme a is not the same as this acetyl coenzyme a so like I said we're basically putting this Mallen coenzyme a away for just a moment because we're going to use it in one of these later steps now once we generate this intermediate the next step is to actually move this acetyl group from this sulfhydryl to this sub hydral shown here and so in step number two all we're doing is we're transferring this acetyl group onto this cysteine which act as a temporary holding group so it holds this molecule in place because ultimately what we're going to do is we're going to combine them and elongate that fatty acid chain so we see that in the next step the cetyl group is transferred on to the cysteine residue as shown in this particular diagram now once we form that what happens next well in the next step this is where the malonyl coenzyme a comes into play so the malonyl coenzyme a that we form in this step now is a reactant in step number three and in step number three what happens is we have another catalytic domain that is part of the FAS molecule known as malonyl trans isolates catalyze the formation of a bond between this molecule here and this sulfhydryl group of that acp group found on that FAS and so we generate this intermediate and now in this intermediate we have that acetyl group attached onto the cysteine and we have the malonate group that is attached onto that sulfhydryl of this acp molecule now one important difference between this catalytic domain and this catalytic domain is this catalytic domain is much more specific for this molecule than this domain is specific for this molecule in fact this domain here can actually bind other carbon molecules in fact it can bind propanil coenzyme a and that's how we're able to actually form our chain fatty acid molecules but in this case we're only going to focus on the even chain fatty acid molecule so once again in step three the malonyl trans oscillates domain of the fatty acid synthase catalyzes the transfer of the malonate group from the malonyl coenzyme a that we formed here onto the acp domain this enzyme domain is highly specific for the malko enzyme a unlike this catalytic domain that is not that specific for this acetyl group and this basically helps prepare the molecule for step four in which we have a condensation step in which we elongate that fatty acid chain so let's take a look at step four now step four is a very important step why well because this is the step that actually drives this entire reaction forward so remember what we did in this step here is we hydrolyze the high energy ATP molecule and we use that energy to actually carboxylate this acetyl coenzyme a to form this Malin cleanse on a now what we do here is a decarboxylation step and we break a thio ester bond and this pre-much releases enough energy for app for us to actually drive this reactant forward so this step is a crucial step in fatty acid synthesis because it drives the overall reaction forward what happens is the enzyme acyl malonyl acp condensing enzyme basically D carboxylates this group and that prepares these two molecules for nucleophilic attack so this nucleophilically attacks this and that breaks this thio ester bond that releases a good amount of free energy so lowers the free energy of this product molecule and that helps drive the equilibrium toward the product side so we ultimately move this acetyl group from the cysteine onto the HCP and we generate this molecule here which we call Osito Osito acetyl coenzyme a settle a CP intermediate so we see that the decarboxylation of the malonate group sets up the reaction for a nucleophilic attack that cleaves the high-energy thio ester bond this bond here and the product of this is acetoacetate attached on to the ACP molecule so this is what we call the condensation step now notice what else this step actually tells us it tells us that even though we used this as a carbon source to actually generate the Malak winds I may in this step here that koa that carbon source namely the carbon dioxide is actually removed and what that implies is all the carbon atoms that are found in that fatty acid chain that is synthesized in this process they come from acetyl coenzyme a and not from that carbon dioxide so carbon dioxide is ultimately removed from that fatty acid chain it does not contribute to those carbon atoms so again very important step because it allows us to drive the equilibrium of this reaction to the product side so ultimately it's the indirect action of ATP that sets up this reaction and allows us to undergo this decarboxylation step that drives this reaction forward now let's move on to step number five so in step number one number five this acetyl as a c2 acetyl group is our reactant molecule now this step number five is a reduction step and the reductant molecule that we use is NADPH so we use NADPH to basically transform this carbonyl group into an alcohol group and we form this molecule as shown here the enzyme domain on that FAS that catalyzed this step is known as beta key to a seal acp reductase it's a reductase because it uses this reducing molecule to actually generate this alcohol from this carbonyl group now we call it beta key to a seal because this is actually a beta keto molecule so when the beta key to a steel acp reductase domain of ACP uses the reducing power nadph we ultimately generate that d3 hydroxybutyrate at we have here so this is a reducing step let's move on to step number six in step number six we ultimately want to actually remove this hydroxyl group and we want to transform this alcohol into a double bond and the enzyme that catalyzes this is three hydroxy acid a CP dehydratase and again this is one of the seven catalytic domains that we find on FAS so in this step we basically have the dehydration step in which these two are the this group and this group are combined to form water they are removed and we form this double bond so the three hydroxy acid a CPD dehydratase domain of FAS catalyzes the dehydration reaction which we generate a double bond and release water thereby forming a molecule that we call Croton ill that is attached onto the acp so we have a condensation step we have a reduction step we have a dehydration step and in step seven this is a second reduction step and again we use NADPH as our reducing molecule so this is catalyzed by the oil acp reductase why well because this molecule here is an annoying it's a trans to trans Delta to Annoying intermediate and so we take this quote nill molecule and we reduce it to basically remove this double bond and basically form this single bond and so we see ultimately when we go from Step five to step seven what we do is we are more specifically when we go from yeah we can say from Step five to step seven we transform this beta keto group to a methylene group that's the point of step steps five through step seven why do we do that well because the fatty so that we generate at the end only contains single bonds so we want to form a saturated fatty acid molecule so in this step we have the second reduction step we generate the butyl group that is shown here attached on to the ACP and this basically completes the first elongation step now what do I say the first elongation step well because all we did so far is generate a fatty acid chain that contains only four

Channel: AK LECTURES

Views: 235,282

Rating: 4.9288793 out of 5

Keywords: fatty acid synthesis, synthesis of fatty acids, fatty acid synthase, creating fatty acids, steps of fatty acid synthesis, reactions of fatty acid synthesis, biochemistry

Id: 4VNKyf34xmI

Length: 16min 8sec (968 seconds)

Published: Sun Apr 10 2016