all right engineers in this video we're going to talk about gluconeogenesis all right so let's decipher this word real quick all right so gluco is meaning glucose right Neo is new and Genesis is to form so in other words we are forming new glucose but to add on to that little uh definition of it is it's we're forming new glucose molecules from non-carbohydrate sources so in other words things like amino acids things like glycerol lactic acid and we'll discuss all of this okay so where is gluconeogenesis occurring what organs would you find uh this gluconeogenic
capability so one is you would find it within the liver so you would find it within the liver and the other one is you could find it within the kidneys particularly the proximal convoluted tubal of the kidneys okay so these are the two organs in which this gluconeogenesis activity is occurring so it's it's forming new glucose molecules from non-carbohydrate sources like amino acids and glycerol and lactic acid and it's occurring in organs such as the liver and the kidneys now now the next question is when is it occurring so we know what it is where
it's occurring now why is it occurring why is this occurring it's occurring because your blood glucose levels are low so that is one of the primary reasons of why this is happening so one of the reasons why is because of low blood glucose levels or we refer to low blood glucose levels as what do we call this we call this high hpo glycemia okay that's one reason another reason is it's for the brain the good old brain the brain completely relies and depends upon glucose so if glucose levels drop the brain becomes affected because the
only source of fuel that the brain prefers to run on is glucose so this is the prim primary source of fuel and you can imagine that any kind of situation where the brain is not getting as fuel you can imagine the dangerous implications that that could could potentially develop from this a secondary source of fuel for this so this is primary source of fuel is glucose but whenever we're fasting for a while and if it if it has to a secondary source that it can utilize of fuel is Ketone bodies and we'll talk about that
when we talk about fat metabolism okay so why is it occurring it's because of low blood glucose levels primarily hypoglycemia and because the brain primarily relies upon glucose it's a primary source of fuel in a situation in which we are having prolonged starvation or certain situations like you're avoiding carbohydrates then this can become secondary source of fuel and it's called Ketone bodies but it is dangerous because Ketone bodies can cause the actual blood to become acidic so it's not preferred and it can lead to keto acidosis okay so we know what it is we know
where it's occurring and we know why it's occurring now let's go on to what's actually happening in this gluconeogenic pathway okay so you guys know the normal way that glucose is coming into the cell right so to recap that let's go ahead and see what happens glucose is brought in through some type of glut transporter but specifically we can say that if it's in the liver we know that it's going to be some type of glut two transporter right we know that the specifically it's going to be a glut two transporter and we also know
that in other different organs too like for example the kidneys it can be a glut three receptor so glut two receptor for the liver and glut three receptor for the kidney now what happens is this glucose is going to come into our cells right when the glucose comes into the cell it actually gets phosphorated right and then it gets turns into glucose I'm going to abbreviate them guys for the sake of popping through this quick glucose 6 phosphate then it gets converted into fructose 6 phosphate then fructose one6 Biz phosphate then it gets split into
fructose I'm sorry and it gets split into glyceride three phosphate and the other component of that is dihydroxy acetone phosphate then it gets converted into 13 BPG then three phosphoglycerate then two phosphoglycerate then phosphoenol pyruvate and then lastly into pyruvate so again it goes g3p 13 BPG 2 PG fosol pyu and pyu now this occurs once with the g3p but then I told you guys from the glycolysis video that dhap can't get converted into 13 BPG so he has to get converted into ga3p so this pathway occurs twice and so I can technically represent that
by actually if I came all the way down here with this guy this guy goes into ga3p and then it goes through this process okay now if you remember I told you there was some important steps one of them was this step right here so let me actually draw the rest of this here and pink and pink is just representing that it's a very important control step this step right here is also an important control step and this step right here is also an important control step now we want to go in the exact opposite
direction of glycolysis so you can think of gluconeogenesis as the reverse process of glycolysis but if you remember I told you that certain pathways are reversible in certain art like this pathway is reversible this is reversible that's reversible reversible reversible reversible right all of the ones that are reversible okay yeah you can go right up that pathway but the ones that are irreversible you have to go around that and that's what we're going to try to explain what's actually happening here so the first thing that we need to do is let's start with the first
one that I'm going to talk about and that's going to be lactic acid so if you're uh let's say that for some situation your muscles your muscles are Contracting right and they're developing a lot of lactic acid so out of that let's say that we have lactic acid come here so here's our lactic acid we're going to represent that as the three carbon cuz it's going to be similar to pyate right so now this actual specifically this lactic acid is going to come into the cell and then what happens is that lactic acid can get
converted into pyruvate right so again who is this guy up here this is lactic acid and this could be coming from the muscles okay now this lactic acid can actually get converted into pyruvate but pyruvate can't go back up to pep so how does he get around that he goes into the mitochondria when he goes actually before I do that let's actually show the other things feeding into this no no we'll actually go through this so now pyruvate what's he going to do he's going to move into the mitochondria when he goes into the mitochondria
what does he get it converted into so here's our pyu right there this is our pyu if you remember the pyu gets converted into AAL Co away but guess what pyruvate's sneaky because you remember there was an enzyme that was controlling this step right here and if you remember the enzyme that was controlling this step let's actually show it again in pink what does it represent if it's pink that means it's a reversible step I mean it's an irreversible step this can't go backwards so pyruvate's really sneaky and he has this special pathway let's represent
it in purple here that he can actually get converted indirect ly right I'm sorry directly he can go straight from pyruvate to this guy what is this guy right here this guy's name is oxaloacetate I'm going to abbreviate it o AA but understand that his name is oxaloacetate pyruvate is three carbons oxaloacetate is four carbons So what had to happen in here you had to put a carbon dioxide or some some form of it into this reaction so the enzyme that's controlling this if you can imagine Whenever You're carboxylating Something adding a carbon into it
you can imagine what the enzyme is actually called this enzyme here that's working here in this step is actually called pyruvate carboxilate so again what is this enzyme called it's called pyrate carboxilate and what this enzyme is doing is it's driving this step so that he makes OAA now oxaloacetate he can't get through the membrane but guess what this guy can this guy here so this step is actually reversible so I'm going to represent this in Black here so we can differentiate from all these other ones so this step is reversible what is this molecule
right here called this molecule right here is called malate now what happens is OA can get converted into malate then this malate can actually get pushed out of the mitochondria when the malate is pushed out of the mitochondria this is really cool it's kind of interesting the way our body does this but this malate gets pushed out when he gets pushed out it's pretty funky what happens but it's it's uh it's cool now look here's our actual malate the malate is going to be acted on by another enzyme and that what's going to happen is
this malate is actually going to be converted into here you go back to oxaloacetate so OA got converted into malate and then malet gets pushed out and then when he gets pushed out he gets reconverted back into oxaloacetate OAA okay so now who is this guy right here who is this one right here this guy specifically our malate and this guy right here is our o oxaloacetate now what happens is oxaloacetate we don't want to convert them into pyruvate because that's not a reversible step what's the next one right above that pep so now what
I'm going to do is is I'm going to take OAA and I'm going to convert that OAA into pep but I have to have an enzyme that can do the opposite of what this enzyme did because what is this P pic carboxilate do he added a carbon because this was three and this was four now I'm going from four carbons to three carbons so what did I have to do I had to remove a CO2 so now I'm pushing a CO2 out of this so now I'm getting rid of CO2 just like I put a
CO2 into this reaction I'm getting rid of it what's another thing that's happening this one doesn't have a phosphate on it this one does so that means that by some mechanism I had to add a phosphate into this so what is the enzyme that that's catalyzing this whole step right here the enzyme that's driving this step is called phospho enol pyu carboxy cyas they refer to it as Pepsi K so again what is this enzyme here called it's called phospho enol pyruvate carboxy kinase so this phosphoenol pyruvate carboxy kinase is stimulating this step here what
is he doing again he's putting a phosphate onto OA and he's getting rid of a carbon in the form of carbon dioxide and then converting it into pep and then where can pep go he can go to two phosphoglycerate three phosphoglycerate 13 bis phosphoglycerate back up to g3p back up to fructose 16 phosphate oh he's stuck now what do you have to do well thankfully God has provided another enzyme at this point right here and this enzyme is called fructose one six bis phosphatase and what this enzyme does is is he helps to trigger the
opposite reaction so you know how this was fructose 16 bis phosphate this enzyme fructose six bis phosphatase will cut the phosphate off of the one carbon so what comes out of this reaction what will actually be released as a result of this you'll release that phosphate that's representing our phosphate this will go up to this point so now you go to fructose 6 phosphate and then fructose 6 phosphate can convert it into glucose 6 phosphate but this glucose 6 phosphate he can't get out where does he have to go he comes over here so now
this glucose 6 phosphate comes over here what is this guy right here called this guy right here is called the smooth endoplasmic reticulum so over here you're going to have your smooth endoplasmic reticulum in the smooth endoplasmic reticulum you have a special enzyme look at this enzyme here it's inside of this actual smooth art so if it's inside of the smooth R you have to bring the glucose inside of the Smoothie R in order for this enzyme to be able to function this enzyme is going to rip that phosphate off of the six carbon of
glucose so look what happens glucose 6 phosphate is going to come in he's going to come in through this channel this is a glut transporter or T1 they call it it's going to move across this enzyme what is this enzyme going to do it's going to rip a phosphate out so now we got rid of that phosphate off of that guy so now what do we have here what will be remaining out of this 1 2 3 4 5 six and then and if you remember if there's six of these guys that is our glucose
where's that glucose going to go that glucose is actually going to exit out through this other glucose transporter they even call it T2 so again this is T1 this is T2 it's going to come out and then where then it can actually go out through a glucose transporter so maybe it can come out through this one and be put into the bloodstream so again what's being put into the bloodstream here if we draw it here one two three four five 1 2 3 four 5 six sorry messing up my counting here sometimes all right so
there's our glucose and then we have into the blood our glucose what was the original problem guys what was the problem of why we had to do this let's come over here why did we have to do it because the blood glucose levels were low what did we just do to the blood glucose levels we brought it up so now now that we've started this whole process we did it specifically showing how that works with this uh lactic acid being converted into pyruvate and then that pyruvate gets pushed in here then what happens to him
he goes and gets acted on by pyruvate carboxilate gets into OAA then he gets converted into Mali Mali gets pushed out here back into OAA worked on by Pepsi K to pep all the way up until it gets stuck at this point fructose 16 bis phosphatase rips that phosphate off takes them up to the next problem which is g6p if you're in the liver and the kidneys you have this enzyme which is called what is this enzyme here called this enzyme is called glucose 6 phosphate so this enzyme is called glucose six phosphatase okay then
it gets converted into glucose because it rips the phosphate off that glucose goes out of the Smoothie R and out back through T2 into this cytoplasm and then gets pushed out of a glucose transporter into the blood and the blood glucose levels goes up what else can contribute to this you see this guy right here this is triglyceride right so this is our triglyceride what is this triglyceride going to do so here is our triglyceride and if you know about triglycerides they're they're actually composed of two components you see this head part of it the
head part of this triglyceride is consisting primarily of what's called glycerol so let's say I put it like a dividing line down here so this component of this side right there is the glycerol that's the head over here all of these little Tails all of these three Tails here one two three that is for your fatty acids okay so triglycerides are broken into two parts glycerol fatty acids what I'm going to do is I'm going to activate some enzyme and that enzyme is going to break this triglyceride into two components one component is going to
be the fatty acids so now let's draw here here's our one fatty acid there's our two fatty acid there's our Three fatty acids okay what's the other component the other component is going to be the glycerol so we have two components here one is the glycerol that we broke it down into and the other one is the fatty acids what is this process called whenever you break down triglycerides into fatty acids and glycerol they call this okay lipolysis okay this glycerol is going to contribute to this process how he bypasses this step he's kind of
Lucky so what the glycerol does is he actually gets acted on by a special enzyme and he gets converted so now let's actually show the glycerol as a rever a result of this reaction here here's our glycerol and then what we're going to do is we're going to put glycerol is three carbons so what we're going to do is we're going to put on the third carbon we're going to chain a glucose on there so what had to happen in this part here there had to be some type of glycerol kinas which puts a phosphate
into this reaction usually in the form of ATP but now we got this glycerol 3 phosphate so what is this molecule here called this molecule is called glycerol specifically it's called glycerol three phosphate that glycerol 3 phosphate is going to get converted into dihydroxy acetone phosphate you see dihydroxy acetone phosphate there's just a little nadh mechanism that works here but dhap where can he go he can go up to fructose six bis phosphate then from fructose six bis phosphate if he's acted on by the fructose one6 bis phosphatase he's converted into fructose 6 phosphate then
from fructose 6 phosphate he's converted into glucose 6 phosphate oh he's stuck where does he go smoothie R what happens in the Smoothie R he gets taken into the Smoothie R by T1 acted on inside of the Smoothie R by the glucose 6 phosphatase enzyme and converted back into glucose taken out of the Smoothie R through T2 and then put out of the blood through the glucose transporter okay now technically I'm not going to mention it but these fatty acids they can be involved in it but generally they're not going to be they're actually going
to get pushed into another pathway um I'm just going to show here with a straight line they will be involved in being converted into aceta and this is called beta oxidation but we'll talk about this there is a phenomenon where the fatty acids if you have what's called odd chain fatty acids so I'll put here as an exception it's insignificant because the amount of odd chain fatty acids that contribute to um specifically glucogenesis is insignificant but some of these odd chain fatty acids they can actually be pushed into this guy right here called suino and
then eventually to malate and then that malate can get pushed out and be contributed through this process but it's so insignificant that it's really not even considered to be a part of that mainly just glycerol okay one more inside of our cells you have proteins that's where a good portion of our actual proteins are going to be primarily found now when you need glucose sometimes your body might have to use some of the amino acids from these proteins so you know what happens whenever you break down proteins so let's say I take this actual protein
and I catabolize this protein so I undergo catabolism of this protein if this protein is catabolized what is that called when you have this this is called again protein catabolism in this process now what I'm going to do is I'm going to break this actual protein into its individual amino acids what I'm going to do now is I'm going to zoom in on one specific amino acid and look at how it's affecting this process so let's say here I have an amino acid but I talk about really some specific ones okay so actually no we
won't do that we'll talk about that individually with uh protein metabolism so what happens with this amino acid this amino acid can react with another mole molecule this molecule that it's going to react with is going to be some type of Keto acid what do I mean by keto acid usually this keto acid is called Alpha keto glutarate there can be another one which is called oxal acid but generally these are usually kreb cycle intermediates what happens is this amino acid and this keto acid are going to react with one another and then as a
result so let's say this amino acid reacts with the keto acid the keto acid is going to be converted into a new molecule this new molecule is now going to be a new amino acid okay generally this new amino acid is usually glutamate okay then this amino acid is actually going to be converted into some type of modified keto acid or just in general a keto acid what do I mean by this it depends upon the amino acid but some of these amino acids inside of our body some of them mainly um one of them
is actually specifically called alanine I'll write it here here specifically one is called alanine this right here this modified keto acid can actually get converted into pyruvate what happens here again specifically this modified keto acid can actually go and be converted into pyruvate where can pyruvate go it can go into forming oxaloacetate via the pyruvate carox then he can get converted into Mali then from Mal he can go back into OA then he can go to pep and then eventually know the whole process it can go back up and make glucose that's one mechanism look
what else can happen with these keto acids this is pretty cool it can come into a specific point of the kreb cycle maybe one of them is a cetal COA okay so maybe one of them is specifically acetyl COA maybe he can actually one of the amino acids can get converted into acetyl COA some of them can actually be converted into specifically other CB cycle intermediates one of them for example is this guy right here this guy right here is actually called Alpha ketoglutarate he can be converted into him there's some of them that can
be converted into other different kreb cycle intermediates like suxo COA or oxy acetate but you get the point what's the overall point of this then these modified keto acids they can be converted into different points one point is they can be converted into pyruvate if it's converted into pyruvate where can that pyu go it can eventually be used to make glucose what if this is actually converted into acetyl COA where does acetal COA go through it goes through all of this process and eventually it goes to OAA or it goes to this malate right and
where can this malate go it can go out here let's say it gets converted into Alpha ketoglutarate where will that eventually go it'll go to malet where will that malet go out here let's see it goes to suin ko suino ko goes to eventually Mallet and goes out here and helps with the making of glucose so it's amazing the way our body performs these processes so now to finish it all off what are the actual substances that can be contributors of gluco neo genesis what are our contributors here one of them we said was lactic
acid which is coming from the muscles the other one is going to be glycerol which is coming from the actual triglycerides the other one is going to be amino acids and then technically if you want to throw this one in there I'm going to do it in a different color because it's not as significant but it would be the odd chain fatty acids okay but again these are not as significant because very little amounts of these are actually contributing to glucon neogenesis last but not least what hormones are helping this process because it's not just
good to know all the things that are involved but what hormones are actually assisting in this process so now let's write down specifically what hormones are involved in glucon neogenesis who's helping this process occur so the main hormone is going to be glucagon which is made by your pancreatic alpha cells nor epinephrine epinephrine so your catacol amines um cortisol and I'm going to put a star next to this guy because his prime Metabolic Effect is going to be gluconeogenesis and we can even say thyroid hormone so even thyroid hormone so I'm going to put thyroid
hormone and then we'll put one more and that's going to be growth hormone G right so again what hormones are contributing to this actual process here glucagon norepinephrine cortisol thyroid hormone and growth hormone these are the main ones that are contributing to the actual gluconeogenesis so we know what gluconeogenesis is it's the formation of glucose from non-carbohydrate sources we know that it's occurring in the liver and in the kidneys primarily the proximal convoluted tubal we know it's occurring because your blood glucose levels are low hypoglycemia so maybe below 70 or 80 milligrams per DL and
it's also occurring because the brain needs glucose it's its primary source of fuel and you don't want it to make Ketone bodies because they're acidic and you understand this whole process of how gluconeogenesis is occurring and you understand the actual three main gluconeogenic factors lactic acid glycerol amino acids and achain fatty acids all right Engineers I hope all of this made sense I hope you guys really enjoyed it if you did hit the like button subscribe leave a comment down in the comment section we look forward to being able to hear from you guys all
right Ninja nerds until next time
