Metabolism | Regulation of Gluconeogenesis

iron engines in this video we're going to specifically talk about the regulation of gluconeogenesis so we've already talked about gluconeogenesis in the pathway that's involved in it and this part remember I told you guys that we were going to talk about what's called the glucose alanine cycle and the Cori cycle and how it's linking the muscles to the liver or vice versa we're going to do that first and then after that I want to talk about those enzymes that pep CK that pyruvate carboxylase and the fructose 1 6 bisphosphate 8 and what's regulating those enzymes okay but first off let's go into these two cycles so the first cycle that we're going to do first is the Cori cycle now if you guys remember I told you that in the muscle we had glycogen right and whenever we had that glycogen we could utilize that specific enzyme which was called glycogen phosphorylase within the muscles right to convert that into glucose 6-phosphate and when he and what enzyme was doing this inside the muscle this was the muscle let's put em glycogen phosphorylase so the muscle glycogen phosphorylase was stimulating this step to break down the glycogen into glucose specifically doing glucose 1-phosphate if we were to be really really particular it actually broke it down into glucose 1-phosphate and then there was another enzyme that converted that glucose 1-phosphate into glucose 6-phosphate if we were being very very specific this was the phospho gluco mutase so we'll put phospho gluco mutase enzyme now this glucose 6-phosphate we set it can't get out of the cell and the skeletal muscles or a different types of muscle tissues do not have that enzyme called glucose 6-phosphate ace that can rip off that faucet remember was in the endoplasmic reticulum this there's no enzyme like that in the muscles so we're going to have to do something else to disguise that glucose in a different form so we can do two things okay so let's say I take off I take off this path here so I come over here and I branch into a different path because this is what we're going to branch into the Cori cycle and then we'll come over back and talk about the glucose alanine cycle so you know glucose 6-phosphate can undergo glycolysis and at the end of glycolysis you produce what's called pyruvate right and then throughout that process of glycolysis I can actually generate a total of two ATP so within the skeletal muscle I can actually generate two ATP if we take into consideration anaerobic processes but then in this glycolysis pathway we end up with pyruvate right pyruvate can't actually be put into the blood in this point we have to do it in a different form so what we're going to do is if you guys remember there was a special molecule you guys probably remember that enzyme it was called lactate dehydrogenase it was the guy that the soldier soldiers were treating on right the bald guy what was he doing the lactate dehydrogenase was acting on pyruvate and what it was doing is it was unloading NADH is onto the pyruvate so was unloading NADH is onto the pyruvate to convert into NAD+ and what was the molecule that was formed as a result of this this was lactic acid what happens to this lactic acid I'm going to take this lactic acid and I'm going to push it out of the muscle cell and into the blood okay so now I'm going to take this lactic acid and I'm going to put this into the blood alright then what I'm gonna do with this lactic acid is I'm going to take it up in the liver so the liver is now going to take up this lactic acid so this lactic acid is going to go through the blood and it's going to get taken up by the liver when it gets taken up by the liver there's another pathway here so now look what happens in here I'm gonna bring this lactic acid in into the liver when I bring it into the liver there's my lactic acid I can reconvert that back into what I can reconvert this back into pyruvate how because you know that let's actually keep this consistent what color was this over there it was actually a pink arrow right so now hi babe pink air here coming up so lactic acid to pyruvate now if you remember there was a specific enzyme catalyzing this step this enzyme was called lactate dehydrogenase this is also present within the liver as in a mini tissues what it's doing is it's stimulating this enzyme but now the pathway is opposite so now in this pathway I'm going to take nad positives and generate in a DHS and then look what I'm gonna do with this pyruvate I can now take this pyruvate and guess what I can do to him in the liver I can take this pyruvate and go backwards up to glucose 6-phosphate what can I do with that glucose 6-phosphate I can take this glucose 6-phosphate now I have in the liver what is that structure in the liver that's really really special you guys remember the endoplasmic reticulum and in the endoplasmic reticulum there was a special enzyme what was that enzyme that was inside of the endoplasmic reticulum that enzyme inside here was called glucose-6-phosphatase and what happens we could take that glucose 6-phosphate off of this glucose so we're going to bring this in through a specific type of transporter like t1 bring it in have it acted on by this enzyme and when it's acted on by that enzyme now you get free glucose and then what did it release off of it it released off a phosphate what was the name of this enzyme this enzyme is specifically called glucose-6-phosphatase that enzyme right there is called glucose-6-phosphatase and this enzyme is only present in the liver or the kidney are also even certain types of tissues within the GI tract particularly the duodenum but now we have this free glucose now we can take that free glucose and transport it out of this endoplasmic reticulum through t2 transporters and bring that glucose out where can that glucose go it can be contributed into the blood so now we can take this glucose now we have here and put that glucose specifically into the blood stream so here's our fleet free glucose so now look what happened you see how I told you that the muscle specifically to break down glycogen but could only break it up to this point and then it stops because it doesn't have the enzyme we got the actual what we got it in the form of we took this glucose in the form of lactic acid we just hit the glucose 6-phosphate in the form of lactic acid and then what do we do we took that lactic acid to the liver and then reconverted it into glucose free glucose that could get put into the blood but you know what a cycle doesn't just end right there it has to go back so what can happen then I could take this glucose into in the cycle I bring the glucose where I bring the glucose back in to this cell and I'll convert it into glucose 6-phosphate right because you know that there's an enzyme that does this step to what is the enzyme that catalyzes this conversion this is called in the liver hexo kinase so what is this cycle here called that we just did this whole cycle that we just did it specifically called D let's write it over here this is specifically the Cori cycle and it's just basically how we're getting the actual glucose from the muscle to the liver to be converted actually into free glucose because really the muscle can only get to glucose 6-phosphate and then it stops because it doesn't have that enzyme now there's another thing that we can do and again what is this process here call whenever we're taking this lactic acid remember when we did gluconeogenesis we take this lactic acid into the liver and we convert that lactic acid into glucose what is this process here called gluconeogenesis so this is the process of gluconeogenesis we're taking the lactic acid and then converting it into glucose in the liver but you know what else the muscle can do it can take and diverse so now let's actually do this in blue and look what else we can do it can convert this glucose 6-phosphate at the pyruvate again alright so here's our pyruvate but then it can take this pyruvate and they can combine it with a specific type of amino acid you know what that amino acid is called that amino acid is called glutamate so now what I'm going to do is I'm going to can take this pyruvate and I'm going to react it with an amino acid called glutamate and what I'm going to do is the glutamate is an amino acid right so it has an amine group on it it's going to transfer his amine group on to pyruvate and then glutamate will actually get converted into alpha ketoglutarate so now what is the result of these two reacting the result is I'm going to get two molecules one molecule I'm going to draw coming off of this reaction that we're not going to be really caring too much about that is called alpha keto glue to rate that is coming from glutamate the other products when the amine group gets transferred onto the pyruvate and it gets transferred onto the pyruvate include gets converted into alanine you know alanine is an amino acid so what did I just do I took glucose 6-phosphate turn it into pyruvate and oh what do you generate out of this process right here what are you generate from this to a PP by anaerobic mechanisms right assuming anaerobic mechanisms I hit the glucose 6-phosphate in the form of pyruvate but then that wasn't good enough then I have to take the glutamate I have to give the glutamate that has you know the amine group on the glutamate I give it to the pyruvate when I give the amine group from glutamate to pyruvate glutamate turns into alpha keto glute array which is a keto acid in the Krebs cycle and then pyruvate gains the amine group and it gets converted into alanine where can this alanine go so now this alanine can get transport in the blood so now look at this this alanine is going to come where this alanine is going to come through the blood alright it's going to come through the blood and then where can it go it can go into the liver what is it going to do in the liver alright so look at this we bring this guy in to the liver so here's our ala knee here's our alanine right there ala mean hope but you've got spelling let's put alanine alle mean so civically alle mean now that I have this alanine what I'm going to do is I'm going to try to get rid of that amine group so I'm going to get rid of that amine group so what I'm going to do is I'm going to take the alanine and you know that there's enzymes inside of the liver that I can actually have here you know I can take this alanine I can combine it with another type of molecule I can combine this with maybe let's say I combine it with alpha keto glue the rate let's say I combine it with alpha keto glue great so I take alanine I combined it with alpha Q to glittery alanine is amino acid he transfers his amine group onto alpha Q to glue to rate as a result Australis in pink here look at this as a result of this reaction these two reacting look what I get coming off of this reaction is going to be the insignificant part you're not allocated glue right he gains the amine group from the alanine when he gains the amine group from the alan he gets reconverted back into glutamate and then we'll talk in another video that this glutamate undergoes what's called oxidative deamination so in other words he'll get rid of his amine group in the form of ammonia and who get regenerated in alpha keto glue to rate and then this will go into the urea cycle and we'll talk about this an amino acid metabolism but for right now we don't care about that we care about what happens is alanine alanine transfers is amine group and alpha ketoglutarate alpha key to good rate transverse is oxygen on the alanine and alanine now becomes something different he becomes pyruvate what can happen with that pyruvate that pyruvate can get converted into what glucose 6-phosphate and then from that glucose 6-phosphate what can happen you get converted back into free glucose and then that glucose thing what can happen with that glucose he can then be taken back to the muscle so then let's actually show this step here that this pyruvate can then get converted into glucose 6-phosphate then from that glucose 6-phosphate what can happen I can take that glucose 6-phosphate have it be acted on by glucose-6-phosphate a's and then that glucose-6-phosphatase what can happen to him that glucose-6-phosphatase can invert the glucose 6-phosphate into free glucose and then put that glucose into the bloodstream what is this process here called when I take this alanine and I basically help to convert it into free glucose glucose thing goes to the liver comes back out as alanine it's called the glucose alanine cycle it's simple alright so again what is this process here called glucose alanine cycle now we talked about the Cori cycle we talked about the glucose alanine cycle now you need to talk about one more thing to finish off you remember those enzymes those specific enzymes that we talked about a lot in gluconeogenesis specifically the three ones specifically Pepsi k which stood for phosphoenolpyruvate carboxykinase and then we had another enzyme this one was called pyruvate carboxylase and then there is one it's not as significant but we should mention it regardless is going to be fructose 1 6 bisphosphate a's so units called fructose 1 6 bisphosphate a's the question at hand is what is regulating these enzymes because we talked about how these enzymes are working we told you what that we know what they do we know that pyruvate carboxylase does what it converts specifically pyruvate into oxaloacetate we know that we know that specifically this pyruvate carboxylase is taking what it's taking the pyruvate and converting it out into oxaloacetate well the next question is what's regulating this enzyme what's stimulating this enzyme you know this enzyme is specifically stimulated by acetyl co egg so acetyl co a can actually allosteric we stimulate this enzyme because you know whenever there's too much acetylcholine that means that there's a lot of krebs cycle activity and that means that we don't need to keep breaking down the glucose we can actually take and get those we can make glucose now so now whenever there's excessive amounts of acetic away it'll stimulate the pyruvate carboxylase or to convert pyruvate into oxaloacetate and then you can also have certain things that could actually inhibit this enzyme what would inhibit this enzyme well there would be the opposite of acetyl chloride maybe coleg could stimulate this enzyme or you could even say low energy signals so maybe certain types of situations in which there is high amounts of ADP so maybe high amounts of ATP which is signaling that there's low energy signals this could stimulate I'm sorry inhibit this enzyme because if you want you're going to want to inhibit this enzyme if there's low energy signals you're going to want to divert this from making glucose and start breaking down glucose to make ATP so this should inhibit this enzyme okay what about Pepsi k Pepsi k is a whole different animal he's actually regulated based upon synthesis you know there's a may very very important hormone in our body that's released during very very long term stress or situations when our blood glucose levels are low or maybe one have a fever it's specifically called cortisol cortisol is a steroid hormone and what cortisol can do is you know he's actually a steroid hormone so you can activate specific genes and he'll activate specific genes that'll synthesize all of these enzymes so look at this upon the presence of cortisol and when is cortisol released cortisol is released whenever your blood glucose levels are really low hypoglycemia and also during stress but more of like the chronic stress okay and what is he going to want to do he's going to want to be able to promote gluconeogenesis so what does you do he synthesizes more pep CKD more pyruvate carboxylase and more fructose 1 6 bisphosphate ace so that we can actually have these enzymes break down all these molecules to make glucose because these enzymes are what are facilitating the making of glucose now we know that specifically cortisol is regulating Pepsi k by stimulating them you know there's other in hormones that are also doing this - not just cortisol but even glucagon glucagon is another hormone that is also going to be helping in this process but specifically the stimulation of Pepsi K or even the stimulation of pyruvate carboxylase via phosphorylation reactions then we can even say technically phosphorylation of this fructose 1 6 bisphosphate days right but specifically house would be on regulating glue gun is helping with in the synthesis of Pepsi k he's helping in the synthesis of pyruvate carboxylase and he's helping in the synthesis of fructose 1 6 bisphosphate ace but if you had to remember the more important one the significant one you need to remember cortisol cortisol is the primary one that's leading to the synthesis of Pepsi k aruba carboxylation fructose 1 6 bisphosphate these if we have more of these then we can have more of these enzymes available for gluconeogenesis one more thing this enzyme he's also heavily regulated you don't know how he's actually regulated so let's actually get rid of this glue gun 1 here because glucagon does in a weird way he regularly dozens I'm in a very very weird way ok you remember this molecule called fructose 2 6 bisphosphate this molecule is a very strong inhibitor of this enzyme now we have to go back for just a second not too long and explain how this fructose 2 6 bisphosphate is made you guys remember we had that by nuclear dimer that component of this actual molecule here we had this guy right here and this guy right here and it was actually broken into two components but it was one enzyme one component the enzyme was phosphofructokinase too and the other one was fructose 2 6 biz phosphatase and this was one whole enzyme if you remember the phosphofructokinase 2 was taking fructose what six phosphate in converting it into fructose 2 6 bisphosphate then this enzyme here fructose to six Biswas potatoes was actually being ripped away so then look here I'm going to do it with a different arrow fructose to six Biswas potatoes can rip off the phosphate off of fructose to 6 bisphosphate and convert it back into fructose 6-phosphate now if you guys remember that there was actually hormones that were activating these guys so what was actually activating well first off before I do that what was this fructose 6-phosphate really good for besides saying absolutely nothing you know fructose 2 6 bisphosphate what was he doing remember that specific molecule phosphofructokinase 1 remember that fructose 2 6 bisphosphate is the strongest stimulator of phosphofructokinase 1 if you have a lot of this enzyme i'm sorry if you have a lot of descriptors to 6 bisphosphate it'll stimulate pfk 1 which will trigger glycolysis but if you want to do the opposite you're going to want to rip off the fructose to 6 bisphosphate so now the question is how would glucagon or epinephrine or norepinephrine regulate this enzyme okay so let's think about this logically this molecule wants to stimulate pfk 1 so i need to get rid of him so these molecules glucagon epinephrine and norepinephrine are going to activate protein kinase a protein kinase a is going to phosphorylate what is he going to phosphorylate he's going to phosphorylate this whole enzyme when he phosphorylates this whole enzyme two things happen when this component of the enzyme is phosphorylated this one the PF k2 right when this enzyme is phosphorylated what happens he is actually going to be what inhibited if he is inhibited this part if it's inhibited if this is phosphorylated this whole enzyme this part is inhibited and this part is stimulated why what would that do I'll give this part is stimulated it'll convert fructose 6 bisphosphate into fructose 6-phosphate what does that mean for the fructose - 6 bisphosphate concentrations his concentration is going to do what it's going to go down if his concentration goes down is he going to be able to stimulate pfk 1 no so he will no longer be able to stimulate pfk 1 another thing is fructose - 6 miss phosphate it is inhibiting this enzyme if there is decreased concentration of this fructose - 6 bisphosphate then what will happen there won't be as much of this guy and what will happen this will stimulate the same time ok so again let's do this one more time there's a by nuclear enzyme consisting of phosphor photo kinase - and fructose 2 6 this phosphatase if you have glucagon epinephrine and norepinephrine they'll activate protein kinase a who will phosphorylate this whole dimer but whole nuclear bomb of protein when it does that it phosphorylates the whole thing when it phosphorylates it inhibits the PF k - portion so he can't convert fructose distillate 6 fructose 6-phosphate into fructose - 6 bisphosphate that part's inhibited but whenever it's phosphorylated activates the fructose - 6 bisphosphate case which cleaves the phosphate off of what the second carbon and converts it into fructose - of fructose 6-phosphate when fructose - 6 bisphosphate concentration decreases he can no longer stimulate PF k 1 so glycolysis is inhibited also when his concentration decreases he no longer is able to inhibit this fructose 1 6 bisphosphate A's and now this fructose 1 6 bisphosphate 8 is released from inhibition and then he can do what he can cleave fructose 1 6 bisphosphate into fructose 6-phosphate which will then help to go and make glucose okay and engineers we covered basically the regulation of gluconeogenesis we covered the quarry cycle and the glucose alanine cycle in this video I hope it all made sense I hope you guys enjoyed it if you did hit that like button subscribe and comment down in the comment section RN engineers until next time

Channel: Ninja Nerd

Views: 181,551

Keywords: metabolism, regulation of gluconeogenesis

Id: ORIx2WYNWqs

Length: 23min 34sec (1414 seconds)

Published: Tue Jun 13 2017