Full transcript
0:00i knizner is in this video we're going
0:08to talk about fatty acid synthesis okay
0:11so let's start it off first off why is
0:15this fatty acid synthesis occurring and
0:17it can occur in various different
0:18tissues now we're going to talk about it
0:20preferentially in the liver but it can
0:22happen in other tissues just so you know
0:23but we're going to start this process
0:26off basically explaining that this is
0:29occurring whenever the blood glucose
0:32levels are high so again this is
0:34occurring whenever you're in what's
0:36called a a fed State so fed State so
0:40you're eating you're taking in food
0:42you're in the absorptive state you're
0:43eating the food you're absorbing the
0:44food it could be whenever your blood
0:46glucose levels are high so you have high
0:49blood glucose levels what happens is
0:54there's going to be a specific hormone
0:57that's going to be regulating this step
0:58and we'll talk about them very very much
1:00in this process but there also is other
1:01hormones that are negatively regulating
1:03this process but the main hormone is
1:05trying to directly stimulate this
1:07process to try to be able to help to
1:09synthesize fatty acids is primarily
1:12going to be that of insulin okay and
1:15it's because insulin is release whatever
1:16your blood glucose levels are high okay
1:19so we know it's occurring when we're in
1:21the fed state so we're eating food or
1:23we're having high blood glucose levels
1:25or there just could be a lot of other
1:27situations too maybe there's a situation
1:29in which there is actually high amounts
1:31of cellular ATP so high amounts of ATP
1:34being produced whenever there is so much
1:39ATP being produced our body just doesn't
1:41want to continue to keep breaking down
1:42molecules instead they want to store
1:45those molecules of something else that
1:47we can utilize later when we need it so
1:48there could be a couple reasons we could
1:50be in the fed state high blood glucose
1:52levels or we could be producing
1:54excessively two months too much amounts
1:56of cellular ATP that our body says okay
1:59too much ATP let's stop breaking down
2:01molecules start building them up and
2:03storing them and we'll use them later
2:04when we need it
2:05how does that occur okay so we have to
2:08start here with a glucose so say we
2:11bring the glucose in obviously through
2:12some type of blood
2:13Porter so I say we bring the glucose in
2:15here there's some type of transporter
2:18and then you know that glucose actually
2:20gets converted into pyruvate right so it
2:22gets converted into pyruvate and then
2:27you remember that the pyruvate was doing
2:29what it was getting pushed into the
2:30mitochondria and it was actually being
2:32converted into acetyl co a and then what
2:37was happening with that acetyl co a if
2:38you guys remember you remember that
2:40acetyl co a was combining with a special
2:42molecule which was called oxaloacetate
2:45and if you remember oxaloacetate in
2:48acetyl co lay or fusing together right
2:50so they were reacting together to form
2:52what molecule they were forming a new
2:54molecule called citrate and if you
2:57remember citrate is actually going to be
2:58a six carbon structure now if you
3:02remember citrate can then be acted on by
3:04another enzyme called aconitase right
3:06and a connotates can do what it can
3:09convert citrate into isocitrate okay and
3:13then if you remember after that
3:14isocitrate can be converted into another
3:16molecule which is called alpha keto glue
3:21to rate the whole point of this is is
3:23that this can go throughout the Krebs
3:25cycle and it can actually produce ATP
3:27right eventually they're making nadh and
3:29fadh2 so we're not going to do all the
3:31recipes but here you get the point it
3:32can go through this process what happens
3:35is though as we start producing too much
3:38cellular ATP right there was too much
3:40ATP if there's too much ATP being
3:44produced our body has a way of being
3:47able to regulate these processes one of
3:51the things that happens is you remember
3:52this enzyme that converts isocitrate
3:53into alpha ketoglutarate when isocitrate
3:57is being converted into alpha ki of GU
3:58rates through a special special type of
4:00enzyme and that enzyme is called ISO
4:05citrate dehydrogenase enzyme if you guys
4:11remember ATP was actually responsible
4:14for allosteric Lee inhibiting this
4:17enzyme if ATP is allosteric ly
4:20inhibiting this enzyme can you convert
4:22isocitrate alpha ketoglutarate no so
4:25then what happens
4:26your isocitrate
4:27arts building up and you can remember
4:30this citrate to isocitrate is reversible
4:33so that means that isocitrate can
4:35actually get converted back into citrate
4:37what happens is is we start actually
4:40developing significant amounts of
4:43citrate now citrate is extremely
4:47interesting because what he can do is he
4:49can pass right through the mitochondrial
4:50membrane and when he passes through the
4:54mitochondria and comes out here there's
4:56a special enzyme waiting for him
4:58what is that enzyme called this enzyme
5:01is going to stimulate this step right
5:03here the citrate he's going to break him
5:06down into two components what are these
5:07two components that help break it down
5:08into so two things will come onto the
5:10citrate reaction he'll get broken down
5:12into one molecule will be a specifically
5:14called oxaloacetate just think about
5:17what he was eventually originally made
5:19of citrate is made up of acetyl co a and
5:22oxaloacetate but you guys have to
5:25remember when acetylcholine Oh a combine
5:29what does it lose it loses a co enzyme a
5:34this enzyme right here is going to take
5:36the citrate and what is it going to do
5:38it's going to take the citrate and cut
5:40the citrate up and turn it back into
5:42oxaloacetate you know oxaloacetate can
5:46be converted back into malate you know
5:49there's a special enzyme right here I
5:50need to make this this reaction special
5:53because this malli is going to pyruvate
5:56when malli is going to pyruvate there's
6:00a very special enzyme involved in this
6:02process this enzyme is called the Mallik
6:07enzyme why is this important because
6:10this step is one of the few steps in the
6:13body where we actually take in a dp+ and
6:19convert him into in a DPH and this is
6:24super important for fatty acid synthesis
6:27you also make this from another pathway
6:29in your body called the pentose
6:31phosphate pathway or the hexose
6:33monophosphate shunt but we'll talk about
6:35that in another video for right now just
6:37realize that you can generate a NADPH
6:39when you're converting
6:40Eliott into pyruvate via the Mallik
6:42enzyme which is stimulating this step
6:44here but then look citrate is being
6:48covered into oxaloacetate and then he's
6:50also going to get broken down into
6:51acetyl co a but you know I see the co a
6:53it has to have the co a on it or it's
6:56just acetate so what has to happen is
6:58this enzyme also has to add in a 1 it
7:01has to add in a coenzyme a so this
7:05enzyme is doing two things one thing is
7:07he's cutting the citrate and converting
7:09them into Oh a a the other one is you
7:11actually going to be adding a coenzyme a
7:13onto this molecule and convert this
7:15other molecule into what acetyl coenzyme
7:21a okay so a CE tool Co a now what is
7:29this enzyme this enzyme is called
7:32citrate lyase so the citrate lyase is
7:40actually doing what it's cutting up the
7:43citrate into oxaloacetate into acetyl co
7:45lay this acetyl co a is going to go
7:47through a special pathway okay now
7:50what's going to happen to be acetic away
7:51the acetyl co a is actually going to go
7:55through a special special enzyme we need
7:57to make this enzyme special because the
7:59most important part of all of this fatty
8:01acid synthesis okay so let's make this
8:04enzyme here because he is extremely
8:07important in this pathway we can't
8:11forget this one this enzyme is called
8:15acetyl co a carboxylase okay ACC and one
8:22of the stand for again acetyl co a
8:29carboxylase enzyme so this acetyl co a
8:32carboxylate enzyme is going to be very
8:34special because he's very highly
8:35regulated within this step okay so now
8:38what is this acetyl co a carboxyl he's
8:39going to do you know he has an important
8:41molecule in him that we need in order
8:43for this process to occur you know that
8:44molecule a that's actually combined onto
8:46him it's called biotin
8:50so we need biotin okay so he's a
8:54carboxylase so what this acetyl co a
8:57carboxylate enzyme is going to do is
8:59this is helical a carboxylic is taken as
9:01acetylcholine and look what's happening
9:03here it's driving this reaction here so
9:08this is siedel a carboxylate contains
9:10biotin which is really really important
9:12because biotin is going to act as a
9:13specific type of coenzyme within this
9:15molecule and what this acetyl co a
9:18carboxylic is going to do is it's going
9:19to add in another carbon and usually you
9:22do that with in the form of co2 or
9:24bicarbonate right so it's going to add
9:26in a carbon onto this acetyl Colet
9:29so see the clay is normally two carbon
9:30molecule but what I'm going to do is I'm
9:33going to take and add another carbon in
9:34the form of carbon dioxide or maybe
9:35bicarb and what's going to happen as a
9:37result of this reaction I'm going to get
9:41what's called Mallon aisle Mallon aisle
9:47Co a and to be consistent let's put that
9:51Co a in orange so to be consistent with
9:53it let's put that Co a in orange so now
9:55we did what we took a two carbon
9:59molecule acetyl co a to convert it into
10:02how many carbons now malonyl-coa is now
10:05three carbon molecule so now we have a
10:07three carbon molecule and we did that by
10:10doing what we did a carboxylation
10:12reaction we added co2 into this reaction
10:14now I told you that this enzyme is very
10:16heavily regulated let's talk about the
10:18there's two types of regulation like you
10:20guys know one type of regulation is
10:24going to be allosteric the other type of
10:30regulation is going to be hormonal so
10:35now the two types of allosteric s-- one
10:37is going to be citrate that's going to
10:39be an allosteric regulator and
10:40specifically he's going to stimulate and
10:42we'll explain that a second the other
10:44allosteric regulator there's actually
10:48going to be cold long-chain fatty acids
10:51with a coenzyme a on it so any type of
10:54long-chain fatty acids with a coenzyme a
10:56on it
10:58these can also control this but
11:01specifically these guys are going to
11:03inhibit the acetyl co a carboxyl is and
11:07we'll explain how and then there's going
11:09to be hormonal so then you can think
11:11about hormonal there's going to be
11:13insulin and insulin is going to want to
11:16stimulate this process and then you're
11:19going to have the opposite of insulin
11:20which is going to be cortisol or
11:25glucagon or epinephrine norepinephrine
11:32they're going to try to oppose this
11:34process now let's go ahead and explain
11:37this now what we have to do is we have
11:39to realize that acetyl co a carboxylase
11:42can exist in two forms and active form
11:44in an inactive form okay so now acetyl
11:46co a carboxyl is going to just in two
11:48forms look at this let's say you know
11:50originally he existing dimers he's
11:51actually an inactive he's in dimers so
11:54say here's a dimer and here's a dimer
11:57let's say I have a couple of these
11:58dimers obviously there's going to be
12:00tons of these to make up this whole
12:01enzyme but in the dimer form so these
12:05are the dimers these are the dimer form
12:07of acetyl co a carboxylase so this is
12:10the dye Marik form of a-c-c acetyl co a
12:17carboxylic and what did I tell you in
12:19this form
12:21he is inactive he's inactive in this
12:24form these dye Marik forms but then what
12:28I can do is when he is stimulated by
12:31certain types of processes like citrate
12:34or insulin so he says he's stimulated if
12:37he is stimulated and again what were
12:40those things that stimulated it citrate
12:41okay let's go ahead and explain that
12:43really quick why would citrate be a
12:45stimulus okay come back over here what
12:50was the reason why we even did this
12:52process because we had too much citrate
12:54and if we're building up so much citrate
12:55okay we need to tell the citrate lyase
12:58okay cut me open and give me Oh a a and
13:01acetyl co a so that I can start this
13:02process I have too much of me so start
13:04shuffling it in and shunting it into
13:07making fat so citrate is going to
13:08stimulate it but then what did I tell
13:10you these long
13:11chain fatty acid colace what are those
13:13the product of fatty acid oxidation
13:16right or they're beginning to go into
13:17fatty acid oxidation if we have so much
13:21fatty acid that we're going to want to
13:22try to oxidize wouldn't you want that to
13:24basically say okay inhibit this enzyme
13:26because now I want to start breaking
13:28them down instead of building them up so
13:30in the contrast what would inhibit this
13:33process long-chain fatty acids with the
13:36Koh a on them but we'll come back to in
13:37a second now citrate can stimulate this
13:40and we'll talk about how insulin does it
13:41in a second but if citrate and insulin
13:45activate this enzyme what it's going to
13:47do is it's going to cause these dimers
13:49to come together and fuse if you fuse
13:52these guys together look what happens I
13:54take all of these dimers how many that
13:57have your ID six right one two three
13:59four five six
14:00all of these dimers are going to be
14:03together and whenever they're actually
14:07polymerized together this is the active
14:10form of acetyl co a carboxylate right
14:15this is the active form and this is the
14:17polymerized form so this is the
14:18polymerized form of acetyl co a
14:26carboxylase so now we know exactly
14:31what's happening then citrate is
14:33allosteric Lee stimulating this enzyme
14:36so let's show that over here so look if
14:37I come over here and I have citrate
14:40citrate is stimulating this enzyme to
14:43drive this reaction but in a condition
14:48in which I don't want to drive this
14:50reaction I don't want to be able to
14:51convert my dimeric form into the
14:53inactive form let's say I want to do the
14:55opposite reaction so if I wanted to do
14:57the opposite reaction I wanted to go
14:59from the polymerized form into the
15:02Dinaric form the inactive form what's
15:05going to be stimulating this we already
15:07said it would be long-chain fatty acids
15:10with a co a right which is a sign of
15:12this that you want to do beta oxidation
15:13so if you want to debate oxidation you
15:15don't want to build up fat so you want
15:17to break them down so that will
15:19stimulate this step going to the
15:21inactive form and already we told you
15:24that
15:24insulin and glucagon can also regulate
15:26these guys and we'll talk about in just
15:27a second okay
15:30now this malum yoco a and this NADPH
15:34they're very important and again I told
15:37you that you can get this NADPH from the
15:38Mallik enzyme but where is another place
15:41that I can get that NADPH that's very
15:43important and we'll talk about in
15:44another video but it's from the pentose
15:47phosphate pathway extremely important
15:54pathway it's responsible for generating
15:57a lot of different things that's
15:58important for our body but it's making
16:00nadh s NADPH s I'm sorry so this is
16:03making tons of NADPH through the
16:04oxidative phase when you're making a lot
16:07of any dphh here and then what else are
16:09you making over here a lot of NADPH is
16:12here these are important because these
16:15are going to be the reducing agents so
16:17again what are these molecules here for
16:18these are your reducing agents you need
16:25these as the precursors to start off
16:28because you know malonyl coenzyme the
16:31next video
16:32he is a precursor for fatty acids he's
16:38going to what we're going to build on
16:40for these fatty acids and you'll see
16:42exactly how in the next video but NADPH
16:45is needed in order for this process to
16:48occur and you'll see why now let's come
16:51back to this thing that we were going to
16:52talk about with insulin and glucagon
16:54okay so let's say that I have insulin
16:59working on this receptor here so let's
17:01say here I have insulin so insulin comes
17:05over here and it binds on to this
17:07receptor when it binds on to this
17:10receptor it leads to the activation of
17:12these molecules which are called phospho
17:15protein phosphatases these false low
17:20protein phosphatase are very very very
17:22important before we talk about what they
17:25do let me explain what glucagon and
17:27epinephrine does it's going to make more
17:29sense now let's say over here binding to
17:33this g-protein coupled receptor I have
17:36glucagon
17:37I have epinephrine I have norepinephrine
17:42these guys are binding to this g-protein
17:44coupled receptor and activating it and
17:46the eventual end product of this
17:48reaction is protein kinase a so now I'm
17:53going to have protein kinase a and
17:55phospho protein phosphatases that I'm
17:57going to explain but let's bring this
17:59over here so it's not too cluttered okay
18:02so let's say we draw again over here I
18:05have the inactive form of ACC acetyl co
18:12a carboxylase and again what was that
18:14form we're just going to write it down
18:16it was the dimer form right so it was in
18:18the Dinaric form so in the dimer form
18:22and then you have the active form of
18:25acetyl co a carboxylase active form of
18:31acetyl co a carboxylase and this is when
18:35it's in the polymer form when you know
18:38taking all those dimers and put them
18:40together so now if I want to take my
18:45dimer and put my dimer into the active
18:48form what do I need to do I need to
18:50polymerize them so that means I wanted
18:52to be active I want to synthesize fats
18:54what did we say would stimulate that one
18:58thing we said was citrate we said
19:01citrate would stimulate done the other
19:04thing is going to be insulin
19:05okay before I explain this we need to
19:08I'll show you something okay let's say
19:10we come down here and I want to go from
19:13my active form to the inactive form and
19:17we already said that what's going to
19:19inhibits going to stimulate this process
19:21we said it would be the long-chain fatty
19:23acids with the coenzyme a on this would
19:26stimulate this pathway but we also said
19:29it could be glucagon okay now that's
19:30where that protein kinase a comes from
19:32that protein kinase a is going to
19:38phosphorylate this active form of the
19:41acetyl co a carboxylic so it's going to
19:43put phosphates on it when he puts
19:46phosphates on to this guy he puts them
19:48into the inactive form of the state of
19:51koi carboxylase so again whenever there
19:53is the protein kinase a which is coming
19:55from who coming from glucagon coming
19:59from epinephrine or from norepinephrine
20:02this is stimulating the formation of
20:04protein kinase a which phosphorylates
20:05the active form of acetyl co a
20:07carboxylase and turns them into the
20:09inactive diametric form so now imagine
20:12that this guy has phosphates on him and
20:15he's inactive if we want to activate him
20:19then we have to bring in those other
20:21molecules and those other molecules were
20:24called phospho protein phosphatases what
20:28were they called this marker sucks will
20:30do phosphate protein phosphatases
20:34phospho protein phosphatases so you can
20:44imagine what these enzymes are going to
20:47be doing there's tons of phosphates on
20:48this diametric form which is keeping it
20:50inactive if I rip off what if I pull off
20:54those phosphates what will it do it'll
20:58turn it back into the active form who is
21:00stimulating this process phospho protein
21:04phosphatases they're ripping off the
21:06phosphates off the dime Eric form of it
21:08the inactive form of it and turning it
21:10back into the active form of it okay so
21:14now we understand how this whole process
21:17occurring so whenever you have a siva
21:18Kawai carboxylase and it's being
21:20phosphorylated its inactive if you have
21:23it specifically having it the phosphates
21:26removed it's no longer in the inactive
21:28form it's in the active form in the
21:30active form it's going to want to make
21:32mal inoculate and the inactive form it
21:34will not want to make malinovka way and
21:36malinovka way is important for fatty
21:38acid synthesis which we will discuss in
21:40the next video
21:41iron is inert so in this video we got
21:43the basic outline that we're going to
21:44need for fatty acid synthesis I hope it
21:46all made sense I hope you guys enjoyed
21:47it in the next video we'll talk about
21:49how we're building those fatty acids up