Fed vs Fasting Metabolism

hi Ron Dr Mike here in this video we're taking a look at the difference between fed State and fasting State metabolism let's take a [Music] look so to begin we need to understand what's happening in the FED State this is immediately after ingesting a meal one important thing that you're going to find in this state is that in your bloodstream so we're going to focus predominately on glucose because it's the primary energy source for number number of important tissues such as neurons or the brain such as the retina and the lens so the eye also the renal medala and also red blood cells as well glucose is very important so immediately after a meal what you're going to find in your bloodstream is your glucose levels are high that's unsurprising now when I say high we need a reference point right so what is the normal blood glucose range normal blood glucose range typically sits between 4 to 6 milles per liter now does that really help anyone at least not within medicine it's pretty tricky to understand the context of that all right let's try and put into context 4 to 6 Mill per liter let's just take the middle of that 5 m per liter that is pretty much equivalent to 0.22 teaspoon of glucose per liter of blood we've got around about 5 L of blood so in in all of our blood we've got around about one heaped teaspoon of glucose so hopefully that puts it into context that's the amount of normal circulating glucose in our entire bloodstream is one heaped teaspoon now we've just had a meal our blood glucose levels go up so it's going above this one teaspoon it can go to more than 2 teaspoons Worth right so it could go to 10 milles per ler but that's going too high we want to drop it back down because we want to maintain homeostasis luckily for us when blood glucose levels are up it goes to the pancreas because blood goes everywhere right it goes to the pancreas and stimulates the release of a hormone called insulin from a specific area called the pancrea pancreatic eyelet cells specifically the beta cells there so that releases insulin now what insulin does in this case is it allows for glucose to leave the bloodstream and enter tissues specifically or predominantly two major tissue types muscle tissue and atap POS or fat tissue tissues like the brain and the liver for example don't need insulin they'll simply suck the glucose in from the bloodstream when the concentration is higher in the blood than in the tissue but because they're not large organs they can't really drop the blood glucose levels enough but we need big tissues like muscle and fat right that makes up most of our body weight but they're insulin dependent and so what they'll do what this insulin does is it will go to the cells and it tells the cell membrane to express a glucose transporter so here's a glucose transporter termed glut glut T and there's different types of glut glut one 2 3 4 so forth and this then allows for the glucose that's in the bloodstream now to into those tissues like the muscle and the fat what happens to this glucose well I want to focus on what happens in a liver cell because the liver is really important at mobilizing all of these nutrients storing and mobilizing so let's now call this a liver cell a hocy the glucose has entered and what will happen is glucose undergo something called glycolysis glycolysis is moving from glucose to glucose 6 phosphate fructose phosphate fructose 16 bis phosphate splits in half remember glucose is a six carbon molecule C6 h126 six carbons and in the process of glycolysis it rearranges those carbons to make it easier to hand off electrons and protons I'll talk about that in a second so as we go through glycolysis it's six carbon to here then it splits into two three carbon molecules now you'll notice that I'm not spending a lot of of time on glycolysis because I've done a video on that if you want all the information required about glycolysis watch the glycolysis video by Dr Mike and two three carbon molecules here now the dihydroxy acetone phosphate which is sometimes written as DAP in your textbooks that will turn into glyceride 3 phosphate which means we end up having two three carbon molecules here so we end up having two glyceride 3 phosphates which means we have 2 13 B phosphoglycerate 2 three phosphoglycerate 22 phosphoglycerate and then that turns into phosph or pyrovate and then pyate that's glycolysis but what's the point of doing this I said well one it's to remove electrons and protons true the other is this as when glucose enters and turns into glucose 6 phosphate we actually use energy to do this we take ATP and it turns into ADP we use energy then at this step we do the same thing we take ATP and we spit out a DP so we use energy hm is this what we want in this process remember we're in a Fed State we got all of this glucose then we go down to here down to here down to here and we take a DP and we generate energy we generate ATP but remember we've got two molecules here so we end up taking two ADP and generating two ATP we've used 2 ATP here we've generated 2 ATP here so we've wiped the Slate clean then as we go from phosphino pyate to pyate we generate two more because there's two phosph or pyruvate there's two pyate so we generate 2 ATP we take 2 ADP and we generate to ATP let's just think about this let's do the maths if we have a look at glycolysis and we look at the net energy production and loss -1 -2 positive 1 positive2 so we WIP the Slate clean positive2 so we've generated positive2 ATP in the process of glycolysis so glycolysis allows for us to generate ATP directly but in addition to that it also takes a molecule called nad+ because there's two here takes two of them and it generates to n a DH plus a free floating hydrogen ion what the hell does this mean this is the molecule NAD plus is the molecule that steals electrons and protons I'll tell you why in a second the details of that are in the glycolysis video so we've also generated two nadh so you can say that the whole reason for bringing glucose into a cell is it generates energy I'll explain that in one sec as we go in now to the crab cycle and pyruvate goes to acetal C and to citrate nutate saate fumerate malate oxyacetate what you'll find is this firstly when pyate turns to acetyl COA acetyl COA must bind with oxaloacetate to form citrate when citrate turns into alha glutarate it takes NAD plus and spits out nadh plus three hyon Alpha key glutarate to suxin will do the same thing thing plus it generates ATP cool then we go from sux to fumerate that takes f a d which is very similar to NAD and produces f a d h and then when we go from um melate to Oxo acetate it generates more NAD D plus 2 NAD h plus three hydrons so what we get here for kreb cycle when it comes to looking at the net energy we've got 1 2 3 nadh we've got one ATP and we've got one fad H2 so the Krab cycle is energy generating now let's talk about we've generated all this nadh nadh fadh2 this is where the electron transport chain comes into play what happens here is that the and I let's draw it in a different color let's draw it in blue the nadh and the fadh to have stolen hydrogen right remember here's NAD plus it's turned into nadh so it's stolen hydrogen remember hydrogen on the periodic table is the first element when it's as a complete atom it has a positive proton and a negative electron flowing around it the negative electron cancels the positive proton out so generally a hydrogen atom is just H but it's got one proton one electron here NAD plus is stolen en a hydrogen fad has stolen two has stolen two hydrogens CU that's supposed to be fadh2 down here my apologies it's stolen two hydrogen which means it's stolen both the proton which is just hydrogen without the electron and the electron so here what it does is it releases the electrons and it releases the protons the hydrogen without the electron now what this means is these proteins of the electron transport chain embedded in the in the membrane they take the electrons and play Hot Potato as you pass electron from protein to protein it excites these proteins it excites them and allows for them to take the hydrogen and pump the hydrogen up into this intermembrane space so now we've got a hydrogen ion concentration that's high in this intermembrane space as we know because of diffusion these hydrogen want to go down the concentration gradient they move through this amazing thing called an ATP synthes which turns this turbine spin spin spin and that generates a huge amount of ATP so effectively the argument you can make and that I'm making right now is that nadh and fadh2 make energy so we can use them as proxies for energy so at the end of the day my point here is that in the FED State what happens is gsus and the creb cycle make a bunch of energy it's energy generating that makes sense we've just fed we make energy but sometimes we don't want to just we don't want to eat and then just use all of that all of those nutrients for energy production right we want to use some of those nutrients so at some point the energy that we produce here the high levels of ATP and the high levels of nadh for example we'll say hey we've got enough we've got enough so it backs up so if these nadh levels are too high think about it it's going to not want to go from NAD plus to nadh because they're already high it's is high if the ATP levels are too high it doesn't want to go from ADP to ATP right so it backs up backs up backs up backs up backs up backs up backs up backs up backs up and it says Hey glucose don't make any more ATP it tells the glucose to turn into glucose 6 phosphate which then turns into glucose one phosphate and glucose one phosphate can be stored as glycogen now glycogen are BAS basically glucose molecules snap together right so that's a storage form so we either in the FED State use glucose to make ATP or we store it as glycogen a lot of this glycogen is stored in the liver in the muscle and in the kidney we store or at least can store around about 190 G of glycogen and we only need around about 160 gram of glycogen for energy in a day so we've got around about 30 hours of glycogen available to us now that's not if you're undergoing exercise or intense manual labor that's just for survival right we've got enough glycogen to last us for 30 hours less if you're doing a lot of exercise so that's the FED State it's mediated by high glucose and high insulin levels and the outcome of that was high ATP high nadh and obviously High fadh two but also high levels of substrates like acetyl COA and citrate let's just write citrate the reason why I'm writing that is because all of these are strong negative Regulators because once they go up it says we've got enough so they're strong negative Regulators of the creb cycle and glycolysis so that's the FED State what's now happening when we've fed but we've stopped eating it's been 3 to 4 hours post eating post prandial what happens well let's have a think our blood glucose levels are going to drop so let's have a look now this was in the FED State let's now have a look in the fasting State again fasting state is anytime after 3 to 4 hours after eating our blood glucose levels go down cool goes down makes sense goes below 4 mm per liter we want to bring it back up so the fasting state is recognized by having dropping blood glucose levels when blood glucose levels drop it doesn't stimulate insulin to be released it stimulates another hormone that's released from the pancreas called glucagon and you can remember this because when glucose is low glucose is gone glucagon glucagon is least when glucose is gone or at least glucose is low it's also going to have low insulin right this is important because here when insulin levels were high not only did allow glucose to enter the cell the insulin allowed for the enzymes of glycolysis to be kicked into action and allowed for the enzymes of the KB cycle to be kicked into action here when glucagon levels are high it inhibits the enzymes at these steps it inhibit inhibits glycolysis it inhibits the enzymes of the creb cycle and inhibits the KB cycle we don't want these two things to be happening in a fasting State why because we don't have enough glucose to do it right so what do we want to do then in this fasting State we want to increase our glucose levels but if we don't have any what can we do well the very first thing we do is break that glycogen down now glucagon is a stimulator of this process now great thing for us is that going from glycogen to glucose one phosphate that's a reversible step so the enzyme used here can be used to go backwards cool from glucose one phosphate to glucose that's a reversible step so that can go backwards but the problem is going from glucose 6 phosphate to glucose in order for that glucose to be able to in this case leave the bloodstream to increase it it can't that's ireverse ible but here's the great thing glucagon when it goes up stimulates the transcription and translation of enzymes here that allow for this reverse to happen so glucagon allows for an enzyme here to be produced and this enzyme is called glucose 6 phosphotase glucose 6 phosphotase and I write it like that just because it's a big term that is mediated by high levels of glucagon so that means now we can take glycogen make glucose throw it into the Bloodstone that's exactly what we do 3 to 4 hours after eating we start to break it down slowly but the thing is it doesn't just use glycogen simultane it will use that predominantly in the front end so between 3 to 8 hours it's predominantly of fasting it's predominantly using glycogen but it's also starting to utilize non-arb hydrate based sources to produce glucose to try and increase that blood glucose level non-carbohydrate that means it's using sources of energy that don't fit into this pathway they have to be fed into that pathway so one for example that we need to talk about is lactate this is probably the most utilized non-carbohydrate based source for energy in a process called glucon neogenesis if you think about the term gluconeogenesis gluco means glucose Neo means new genesis means the beginning of think about that backwards the beginning of new glucose that's what we're trying to make here from non-carbohydrate based sources first one I want to talk about is lactate now what is lactate where does it come from sometimes people term it lactic acid which I think is a Mis Noma lactate is more accurate lactate can come from muscle so remember but muscle needs glucose uses glucose for energy but and to undergo this whole process but one thing I didn't tell you here was that we might use all these electrons and protons to generate ATP but then what happens to all the electrons and protons that are left over electrons are damaging to the body right protons make the area or the environment acidic we got to get rid of this stuff what do we do we have oxygen the great thing is we can take oxygen and oxygen will bind to the electrons and protons what it's going to do is it's going to produce if we snap hydrogen and oxygen together what do you think it produces produces water innocuous water that our body needs but it requires oxygen so this whole process will only happen all the way to the electron transport chain if oxygen is available if oxygen isn't available that backs up this back up and it backs up to pyruvate now this is the thing in the muscle when we are doing um sprinting or we're lifting weights really fast really quickly in a way that we're trying to produce more we need more ATP than we can make with the available oxygen so we don't have enough oxygen basically the py this all backs up to pyruvate and pyruvate turns into lactate this is in the muscle not in the H side here but in the muscle so muscle will produce lactate now the great thing is that lactate will jump into the bloodstream enter the liver cell and will turn back into pyruvate brilliant because in the liver pyruvate can turn into glucose so in the muscle that lactate is useless it can't turn into glucose for energy so it must jump into the bloodstream so from the muscle the lactate jumps into to the bloodstream enters in the liver and goes from lactate to pyruvate now the thing is you might be looking here and going yeah but going from pyruvate to phosph and pyate that's irreversible we can't go from there to there and then go all the way back up as you right so what happens all right let's take a look when muscle makes lactate and turns into pyruvate pyruvate will enter the mitochondria and will turn into a CTO Co no it won't pyruvate will turn straight into oxaloacetate now this is where that glucagon comes into play remember I told you it switched on glucose 6 phosphatase glucagon will switch on an enzyme here called pyruvate carboxylase pyruvate carboxylase which turns pyruvate to oxaloacetate pyruvate to oxaloacetate this this uses ATP we need ATP in this process now oxaloacetate can turn into mallate that's no problem and what happens is mallate will leave go back into the cazol and what mallate will do is mate will turn back into oxy acate now you might think wait a minute oxalacetate oxaloacetate to melate melate back to oxaloacetate what does an oxaloacetate just leave it can't because of its structure oxaloacetate cannot leave and pass through the membranes of the mitochondria but remember here I said when melate goes to Oxo acetate it produces nadh but when oxalacetate goes to mate it goes backwards so that also means when melate goes to oxaloacetate nadh so again reversible I'm not going to write it up there's no point writing up because it's happening there but the thing is oxyacetate doesn't turn to pyrovate it turns into phosphino pyate so as you can see when blood glucose levels are low and glucon levels are high glucagon stimulates glucose 6 phosphatase to allow for glycogen to be produced into glucose it produces pyate carboxy ASE for that to happen and pushes it down into this process and stimulates this enzyme here which is called phosph pyruvate carboxy kinase that's a great name isn't it we can write phosphor py p carboxy carnise and so that turns to phosph or pyate and then look it can go backwards backwards backwards backwards backwards uhoh can't go backwards here it's okay glucagon allows for another enzyme to be released so that it can go backwards in that's called fructose I've wipe that out accidentally fructose 16 B phosphor tase fructose six bis phosphor tase now what can we do we can take lactate and turn it to pyruvate pyruvate can turn into oxaloacetate which turns to melate which turns back to oxaloacetate which turns to phosphino pyruvate which goes back back back back back back back glucose lactate can turn into glucose and that can jump into the bloodstream and feed back to the muscle cell itself awesome now muscle isn't the only producer of lactate red blood cells produce lactate as well so they both produce lactate now why red blood cells remember red blood cells have they're just packed with oxygen they have no mitochondria if they've got no mitochondria this doesn't happen it ironically red blood cells might be packed with oxygen but it can't use it for the electron transport chain because it doesn't have one so all red blood cells can do is glycolysis what's the end stage of glycolysis pyruvate what are you going to do with pyruvate when you're done with it turns to lactate but remember red blood cells can't so when glucagon making these really important enzymes here this only happens in the liver and the kidneys it doesn't happen in the muscle it doesn't happen in the brain which means this process of gluconeogenesis which ultimately is taking pyruvate to make glucose again it only happens in the liver and kidneys that's why when muscle and red blood cells make something like lactate it has to deliver it to the liver so the liver can undergo gluconeogenesis super important Point super important all right so we've got lactate that is an energy source in this process you can also use uh amino acids as well and amino acids come from proteins and muscle and one important amino acid is alanine it's probably the most utilized amino acid for glucer Genesis and it again jumps to pyruvate which we've spoken about that process but there's other amino acids that can jump in like glutamate for example we know that glutamate can be made from a range of other amino acids too but that can turn into Alpha glutarate and there's amino acids that can jump in here and amino acids that can jump in here for example and other discrete areas so amino acids can be used as a substrate to make glucose to increase blood glucose levels here's another Point we've also got triglycerides right triglycerides or triglycerides depending on what you want to call them that's fat right it's in atopos tissue predominantly and triglycerides are made up of glycerol and fatty acids so the triglycerides will split off and release the glycerol and will release the fatty acids all right let's first look at glycerol glycerol thankfully can turn into dihydroxy acetone phosphate now what does that mean glycerol Di axone phosphate can go back yep yep yep yep glucose glycerol can turn into glucose so not only is lactate a source and amino acids a source but glycerol is a source for glucono Genesis these are the three major glucogenic sources glycerol lactate and amino acids you might be thinking what about fatty acids I'll get there in a sec but let's talk about fasting right let's say you've woken up from sleep you've slept 8 hours you haven't eaten in 8 hours so you've been fasting for 8 hours after this time what you're going to find is that after this 8 hours glycogen will be contributing around about let's use blue glycogen will be contributing around about 40 to 70% of the glucose production after 8 hours lactate will be contributing around about 7 to 18% amino acids like alanine will be contributing around about 5 to 11% and glycerol will be contributing around sorry other way around glycerol will be contributing around about 5 to 11% and amino acids will be contributing around about 3 to 5% so as you can see outside of glycogen lactate is the major gluconeogenic substrate that's important now that's after eight hours what do you think happens after 14 hours for example so after 14 hours what you're going to find is that these gluconeogenic substrates they will be contributing 54% of the glucose after 22 hours of fasting they move up to contributing to 64% of the glucose which means glycogen is dropping right after 42 hours so we're nearly at 2 days here glucogenic substrates contribute 84% of the glucose because again the point is to increase blood glucose why why do we want to increase increase blood glucose why don't we just want to make energy because blood glucose levels are important because that's what the brain uses that's what red blood cells use that's predominantly what muscles will use that's also what the retina and renal medala uses so we need the glucose levels to be normal in the blood stream that's important because if you think about this process taking pyruvate right because ultimately a lot of glucon Genesis is going from pyruvate through this uses energy you can see energy is used here for example energy is going to be used here we take GTP and turn it into GDP so we use energy we use energy we also use energy here right by reversing this we take a TP and turn into ADP here we take NAD H and turn it into NAD plus so as you can see we lose ATP here we lose a uh ATP effectively here we lose ATP here we lose nadh here so when we look at the process of gluconeogenesis glucon Neo Genesis net you end up getting you lose one you lose 2 ATP you lose three ATP and you've lost an nadh but remember we've got two of these so we lose a lot right let's just say if we do it from one we end up losing uh 1 2 uh 2 ATP we lose around about -2 ATP -1 GTP and -1 NAD but my point is that glucan Genesis needs energy it needs energy and you might be thinking but wait a minute wait a minute wait a minute my blood glucose levels are low I've got no energy I'm fasting right I'm 12 14 22 42 hours of fasting I need energy I don't have energy so how can I undergo glucan Genesis to make glucose if I don't have any available energy well this is where the fatty acids come into play the fatty acids will turn into AOA at least the even chain fatty acids will this process is called beta oxidation and the great thing about beta oxidation is it produces nadh and fadh2 which I told you what do they do they produce ATP so effectively you can and this changes depending on the fatty acid get around about 4 ATP molecules just in the process of beer oxidation taking fatty acids to turn into acetal COA this is the energy that's used to feed gluconeogenesis hopefully that makes sense but let's think even more long term right we're going 48 hours and above think about this if we want to make glucose ultimately we're doing it by turning pyate pyate into oxaloacetate but oxaloacetate is getting dragged out of here right in the form of malate so to create glucose think about the CB cycle we're pulling oxaloacetate out but I told you we need oxaloacetate to bind to acetal COA when we break down fats which we do when we're fasting fatty acids are turning into acetal COA so we're increasing our aceta levels but decreasing our oxaloacetate levels because it's being taken out and turning into glucose aceto needs to bind to oxaloacetate to make energy but it can't so acet COA just starts to accumulate all these fatty acids turn into AET Co accumulate accumulate accumulate and they snap together now when acetal COI snaps together it forms something called ketones like beta hydroxybutyrate for example that's a ketone what the ketones do is they can jump into the bloodstream and go to the brain the brain will take those ketones and let's pretend that this is the brain it takes those ketones throws it into the mitochondria and turns it into a cal COA so it can enter the crabs you might be thinking wait the oxaloacetate is gone not in the brain remember only in the liver does this process of gluconeogenesis occur so it's only in the liver where the oxyacetate levels are low because it's trying to make glucose in the brain you're going to have normal oxaloacetate levels but the problem is you're going to have low acetal COA levels in the brain because you don't have any glucose to make it right so luckily ketones can make a cal Co and then you can make all the energy that your brain well not all of it because ketones are a bit of a sluggish way to produce ATP but it can make ATP so that is the difference between fed and fasting State metabolism I'm Dr Mike I hope that made sense hi everyone Dr Mike here if you enjoyed this video please hit like And subscribe we've got 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Channel: Dr Matt & Dr Mike

Views: 5,755

Keywords: fed, fasting, fast, metabolism, state, post, prandial, starvation, glucose, glycolysis, glycogen, gycogenolysis, gluconeogenesis, ketones, ketosis, ketogenesis, health, fitness, liver, krebs, tca, citric, cycle, acid, etc, electron transport chain, nad+, nadh, fad, fadh2, lactate, lactic acid, medicine, nursing, doctor, nurse, biomed, class, lecture, professor, university, college, workshop, forum, biology, biochemistry, biochem

Id: eRDnzU8M-vA

Length: 35min 57sec (2157 seconds)

Published: Fri Apr 26 2024