Metabolism | Fatty Acid Synthesis: Part 1

i knizner is in this video we're going to talk about fatty acid synthesis okay so let's start it off first off why is this fatty acid synthesis occurring and it can occur in various different tissues now we're going to talk about it preferentially in the liver but it can happen in other tissues just so you know but we're going to start this process off basically explaining that this is occurring whenever the blood glucose levels are high so again this is occurring whenever you're in what's called a a fed State so fed State so you're eating

you're taking in food you're in the absorptive state you're eating the food you're absorbing the food it could be whenever your blood glucose levels are high so you have high blood glucose levels what happens is there's going to be a specific hormone that's going to be regulating this step and we'll talk about them very very much in this process but there also is other hormones that are negatively regulating this process but the main hormone is trying to directly stimulate this process to try to be able to help to synthesize fatty acids is primarily going to

be that of insulin okay and it's because insulin is release whatever your blood glucose levels are high okay so we know it's occurring when we're in the fed state so we're eating food or we're having high blood glucose levels or there just could be a lot of other situations too maybe there's a situation in which there is actually high amounts of cellular ATP so high amounts of ATP being produced whenever there is so much ATP being produced our body just doesn't want to continue to keep breaking down molecules instead they want to store those molecules

of something else that we can utilize later when we need it so there could be a couple reasons we could be in the fed state high blood glucose levels or we could be producing excessively two months too much amounts of cellular ATP that our body says okay too much ATP let's stop breaking down molecules start building them up and storing them and we'll use them later when we need it how does that occur okay so we have to start here with a glucose so say we bring the glucose in obviously through some type of blood

Porter so I say we bring the glucose in here there's some type of transporter and then you know that glucose actually gets converted into pyruvate right so it gets converted into pyruvate and then you remember that the pyruvate was doing what it was getting pushed into the mitochondria and it was actually being converted into acetyl co a and then what was happening with that acetyl co a if you guys remember you remember that acetyl co a was combining with a special molecule which was called oxaloacetate and if you remember oxaloacetate in acetyl co lay or

fusing together right so they were reacting together to form what molecule they were forming a new molecule called citrate and if you remember citrate is actually going to be a six carbon structure now if you remember citrate can then be acted on by another enzyme called aconitase right and a connotates can do what it can convert citrate into isocitrate okay and then if you remember after that isocitrate can be converted into another molecule which is called alpha keto glue to rate the whole point of this is is that this can go throughout the Krebs cycle

and it can actually produce ATP right eventually they're making nadh and fadh2 so we're not going to do all the recipes but here you get the point it can go through this process what happens is though as we start producing too much cellular ATP right there was too much ATP if there's too much ATP being produced our body has a way of being able to regulate these processes one of the things that happens is you remember this enzyme that converts isocitrate into alpha ketoglutarate when isocitrate is being converted into alpha ki of GU rates through

a special special type of enzyme and that enzyme is called ISO citrate dehydrogenase enzyme if you guys remember ATP was actually responsible for allosteric Lee inhibiting this enzyme if ATP is allosteric ly inhibiting this enzyme can you convert isocitrate alpha ketoglutarate no so then what happens your isocitrate arts building up and you can remember this citrate to isocitrate is reversible so that means that isocitrate can actually get converted back into citrate what happens is is we start actually developing significant amounts of citrate now citrate is extremely interesting because what he can do is he can

pass right through the mitochondrial membrane and when he passes through the mitochondria and comes out here there's a special enzyme waiting for him what is that enzyme called this enzyme is going to stimulate this step right here the citrate he's going to break him down into two components what are these two components that help break it down into so two things will come onto the citrate reaction he'll get broken down into one molecule will be a specifically called oxaloacetate just think about what he was eventually originally made of citrate is made up of acetyl co

a and oxaloacetate but you guys have to remember when acetylcholine Oh a combine what does it lose it loses a co enzyme a this enzyme right here is going to take the citrate and what is it going to do it's going to take the citrate and cut the citrate up and turn it back into oxaloacetate you know oxaloacetate can be converted back into malate you know there's a special enzyme right here I need to make this this reaction special because this malli is going to pyruvate when malli is going to pyruvate there's a very special

enzyme involved in this process this enzyme is called the Mallik enzyme why is this important because this step is one of the few steps in the body where we actually take in a dp+ and convert him into in a DPH and this is super important for fatty acid synthesis you also make this from another pathway in your body called the pentose phosphate pathway or the hexose monophosphate shunt but we'll talk about that in another video for right now just realize that you can generate a NADPH when you're converting Eliott into pyruvate via the Mallik enzyme

which is stimulating this step here but then look citrate is being covered into oxaloacetate and then he's also going to get broken down into acetyl co a but you know I see the co a it has to have the co a on it or it's just acetate so what has to happen is this enzyme also has to add in a 1 it has to add in a coenzyme a so this enzyme is doing two things one thing is he's cutting the citrate and converting them into Oh a a the other one is you actually going

to be adding a coenzyme a onto this molecule and convert this other molecule into what acetyl coenzyme a okay so a CE tool Co a now what is this enzyme this enzyme is called citrate lyase so the citrate lyase is actually doing what it's cutting up the citrate into oxaloacetate into acetyl co lay this acetyl co a is going to go through a special pathway okay now what's going to happen to be acetic away the acetyl co a is actually going to go through a special special enzyme we need to make this enzyme special because

the most important part of all of this fatty acid synthesis okay so let's make this enzyme here because he is extremely important in this pathway we can't forget this one this enzyme is called acetyl co a carboxylase okay ACC and one of the stand for again acetyl co a carboxylase enzyme so this acetyl co a carboxylate enzyme is going to be very special because he's very highly regulated within this step okay so now what is this acetyl co a carboxyl he's going to do you know he has an important molecule in him that we need

in order for this process to occur you know that molecule a that's actually combined onto him it's called biotin so we need biotin okay so he's a carboxylase so what this acetyl co a carboxylate enzyme is going to do is this is helical a carboxylic is taken as acetylcholine and look what's happening here it's driving this reaction here so this is siedel a carboxylate contains biotin which is really really important because biotin is going to act as a specific type of coenzyme within this molecule and what this acetyl co a carboxylic is going to do

is it's going to add in another carbon and usually you do that with in the form of co2 or bicarbonate right so it's going to add in a carbon onto this acetyl Colet so see the clay is normally two carbon molecule but what I'm going to do is I'm going to take and add another carbon in the form of carbon dioxide or maybe bicarb and what's going to happen as a result of this reaction I'm going to get what's called Mallon aisle Mallon aisle Co a and to be consistent let's put that Co a in

orange so to be consistent with it let's put that Co a in orange so now we did what we took a two carbon molecule acetyl co a to convert it into how many carbons now malonyl-coa is now three carbon molecule so now we have a three carbon molecule and we did that by doing what we did a carboxylation reaction we added co2 into this reaction now I told you that this enzyme is very heavily regulated let's talk about the there's two types of regulation like you guys know one type of regulation is going to be

allosteric the other type of regulation is going to be hormonal so now the two types of allosteric s-- one is going to be citrate that's going to be an allosteric regulator and specifically he's going to stimulate and we'll explain that a second the other allosteric regulator there's actually going to be cold long-chain fatty acids with a coenzyme a on it so any type of long-chain fatty acids with a coenzyme a on it these can also control this but specifically these guys are going to inhibit the acetyl co a carboxyl is and we'll explain how and

then there's going to be hormonal so then you can think about hormonal there's going to be insulin and insulin is going to want to stimulate this process and then you're going to have the opposite of insulin which is going to be cortisol or glucagon or epinephrine norepinephrine they're going to try to oppose this process now let's go ahead and explain this now what we have to do is we have to realize that acetyl co a carboxylase can exist in two forms and active form in an inactive form okay so now acetyl co a carboxyl is

going to just in two forms look at this let's say you know originally he existing dimers he's actually an inactive he's in dimers so say here's a dimer and here's a dimer let's say I have a couple of these dimers obviously there's going to be tons of these to make up this whole enzyme but in the dimer form so these are the dimers these are the dimer form of acetyl co a carboxylase so this is the dye Marik form of a-c-c acetyl co a carboxylic and what did I tell you in this form he is

inactive he's inactive in this form these dye Marik forms but then what I can do is when he is stimulated by certain types of processes like citrate or insulin so he says he's stimulated if he is stimulated and again what were those things that stimulated it citrate okay let's go ahead and explain that really quick why would citrate be a stimulus okay come back over here what was the reason why we even did this process because we had too much citrate and if we're building up so much citrate okay we need to tell the citrate

lyase okay cut me open and give me Oh a a and acetyl co a so that I can start this process I have too much of me so start shuffling it in and shunting it into making fat so citrate is going to stimulate it but then what did I tell you these long chain fatty acid colace what are those the product of fatty acid oxidation right or they're beginning to go into fatty acid oxidation if we have so much fatty acid that we're going to want to try to oxidize wouldn't you want that to basically

say okay inhibit this enzyme because now I want to start breaking them down instead of building them up so in the contrast what would inhibit this process long-chain fatty acids with the Koh a on them but we'll come back to in a second now citrate can stimulate this and we'll talk about how insulin does it in a second but if citrate and insulin activate this enzyme what it's going to do is it's going to cause these dimers to come together and fuse if you fuse these guys together look what happens I take all of these

dimers how many that have your ID six right one two three four five six all of these dimers are going to be together and whenever they're actually polymerized together this is the active form of acetyl co a carboxylate right this is the active form and this is the polymerized form so this is the polymerized form of acetyl co a carboxylase so now we know exactly what's happening then citrate is allosteric Lee stimulating this enzyme so let's show that over here so look if I come over here and I have citrate citrate is stimulating this enzyme

to drive this reaction but in a condition in which I don't want to drive this reaction I don't want to be able to convert my dimeric form into the inactive form let's say I want to do the opposite reaction so if I wanted to do the opposite reaction I wanted to go from the polymerized form into the Dinaric form the inactive form what's going to be stimulating this we already said it would be long-chain fatty acids with a co a right which is a sign of this that you want to do beta oxidation so if

you want to debate oxidation you don't want to build up fat so you want to break them down so that will stimulate this step going to the inactive form and already we told you that insulin and glucagon can also regulate these guys and we'll talk about in just a second okay now this malum yoco a and this NADPH they're very important and again I told you that you can get this NADPH from the Mallik enzyme but where is another place that I can get that NADPH that's very important and we'll talk about in another video

but it's from the pentose phosphate pathway extremely important pathway it's responsible for generating a lot of different things that's important for our body but it's making nadh s NADPH s I'm sorry so this is making tons of NADPH through the oxidative phase when you're making a lot of any dphh here and then what else are you making over here a lot of NADPH is here these are important because these are going to be the reducing agents so again what are these molecules here for these are your reducing agents you need these as the precursors to

start off because you know malonyl coenzyme the next video he is a precursor for fatty acids he's going to what we're going to build on for these fatty acids and you'll see exactly how in the next video but NADPH is needed in order for this process to occur and you'll see why now let's come back to this thing that we were going to talk about with insulin and glucagon okay so let's say that I have insulin working on this receptor here so let's say here I have insulin so insulin comes over here and it binds

on to this receptor when it binds on to this receptor it leads to the activation of these molecules which are called phospho protein phosphatases these false low protein phosphatase are very very very important before we talk about what they do let me explain what glucagon and epinephrine does it's going to make more sense now let's say over here binding to this g-protein coupled receptor I have glucagon I have epinephrine I have norepinephrine these guys are binding to this g-protein coupled receptor and activating it and the eventual end product of this reaction is protein kinase a

so now I'm going to have protein kinase a and phospho protein phosphatases that I'm going to explain but let's bring this over here so it's not too cluttered okay so let's say we draw again over here I have the inactive form of ACC acetyl co a carboxylase and again what was that form we're just going to write it down it was the dimer form right so it was in the Dinaric form so in the dimer form and then you have the active form of acetyl co a carboxylase active form of acetyl co a carboxylase and

this is when it's in the polymer form when you know taking all those dimers and put them together so now if I want to take my dimer and put my dimer into the active form what do I need to do I need to polymerize them so that means I wanted to be active I want to synthesize fats what did we say would stimulate that one thing we said was citrate we said citrate would stimulate done the other thing is going to be insulin okay before I explain this we need to I'll show you something okay

let's say we come down here and I want to go from my active form to the inactive form and we already said that what's going to inhibits going to stimulate this process we said it would be the long-chain fatty acids with the coenzyme a on this would stimulate this pathway but we also said it could be glucagon okay now that's where that protein kinase a comes from that protein kinase a is going to phosphorylate this active form of the acetyl co a carboxylic so it's going to put phosphates on it when he puts phosphates on

to this guy he puts them into the inactive form of the state of koi carboxylase so again whenever there is the protein kinase a which is coming from who coming from glucagon coming from epinephrine or from norepinephrine this is stimulating the formation of protein kinase a which phosphorylates the active form of acetyl co a carboxylase and turns them into the inactive diametric form so now imagine that this guy has phosphates on him and he's inactive if we want to activate him then we have to bring in those other molecules and those other molecules were called

phospho protein phosphatases what were they called this marker sucks will do phosphate protein phosphatases phospho protein phosphatases so you can imagine what these enzymes are going to be doing there's tons of phosphates on this diametric form which is keeping it inactive if I rip off what if I pull off those phosphates what will it do it'll turn it back into the active form who is stimulating this process phospho protein phosphatases they're ripping off the phosphates off the dime Eric form of it the inactive form of it and turning it back into the active form of

it okay so now we understand how this whole process occurring so whenever you have a siva Kawai carboxylase and it's being phosphorylated its inactive if you have it specifically having it the phosphates removed it's no longer in the inactive form it's in the active form in the active form it's going to want to make mal inoculate and the inactive form it will not want to make malinovka way and malinovka way is important for fatty acid synthesis which we will discuss in the next video iron is inert so in this video we got the basic outline

that we're going to need for fatty acid synthesis I hope it all made sense I hope you guys enjoyed it in the next video we'll talk about how we're building those fatty acids up