Reciprocal Regulation of Gluconeogenesis and Glycolysis

just like like Allah sees the process of gluconeogenesis must be closely regulated by the cells of our body and what's even more interesting is these two processes so glycolysis and gluconeogenesis are actually regulated in a reciprocal fashion and what that means is when one of these processes takes place in the cell of our body the other process is essentially turned off now the question is why why is it that these two processes cannot take place in a cell at the same exact moment in time well actually they can take place at the same exact moment in time if we examine energy values so there's actually no energy barrier that is actually inhibiting these two processes from taking place at the same exact moment in time why well because remember both of these processes gluconeogenesis and glycolysis release a certain amount of energy in the cell and that means they are both spontaneous exergonic reactions so if we simply sum up these two reactions they will create a net exergonic reaction out what actually doesn't allow these two steps to take place at the same exact moment in time are these special allosteric enzymes as we'll discuss in this lecture so the cell actually uses allosteric enzyme addict regulation to essentially prevent both of these processes from taking place at the same exact moment in time but the natural question might be why well the answer lies in the following explanation so recall that in gluconeogenesis even though we release a certain amount of energy it's an exergonic process we use up four ATP molecules and two gtp molecules while in the glycolysis process we produce on that amount of two ATP molecules so if we sum up these two reactions we'll see that the sum actually uses up to ATP molecules and two gtp molecules and what that means is when glycolysis takes place at the same exact time as gluconeogenesis we're not actually going to form any ATP molecules in fact we're going to use up these ATP molecules and that kind of defeats the purpose of glycolysis and so that's pretty much why these two processes don't take place at the same exact moment of time inside our cell now the next question is how is this actually achieved how can ourselves regulate this process how can the cells actually turn off one process while turning on the other process well it's a result of what I mentioned just a moment ago it's the fact that our cells have these enzymes allosteric enzymes that can be used to regulate this process and there are two points along the pathway so point number one and point number two where we have allosteric enzymes that can be used to basically regulate the pathways of gluconeogenesis and glycolysis so remember gluconeogenesis use it pi uses pyruvate molecules to form glucose while glycolysis uses glucose to form the pyruvate molecule so going this way is glycolysis but going this way is gluconeogenesis okay so let's begin by imagining that inside our cell of the body we have lots of ATP molecules so the energy value the energy charge in a cell is high now remember that the energy charge of a cell is simply the ratio of ATP molecules to a MP molecules and so if the energy charge of the cell is high we have a large ATP level compared to the A&P and if we have many ATP molecules in a Cell will the cell actually need to make any more ATP molecules and the answer is no if there are many ATP molecules the cell doesn't actually need to form any more ATP molecules and in this particular case glycolysis essentially be shut off now because we have an excess amount of ATP these ATP molecules can now be used by gluconeogenesis remember it uses up four ATP and two GTP and so we can undergo gluconeogenesis and use that excess amount of ATP to actually produce glucose and then use that glucose to form glycogen so basically to form the glycogen storages in our cells now what exactly regulates this process so again in our cell we have high energy charge and that will favor the process of gluconeogenesis so let's see how this process is actually activated when we have lots of ATP in our cell well let's begin with this first molecule here so this is our pyruvate carboxylase which is the enzyme that catalyzes step 1 in gluconeogenesis and we have a molecule known as acetyl coenzyme a that essentially activates pyruvate carboxylase it essentially increases its efficiency of converting pyruvate into oxaloacetate so remember in our discussion of this step we said that the assets of coenzyme a is needed to actually allow the binding between the carbon dioxide and the biotin component of that pyruvate carboxylase now acetyl coenzyme a is actually a molecule that is needed for the citric acid cycle to actually take place and so if we have plenty of acetyl coenzyme a molecules that means we have plenty of molecules that are needed for the citric acid cycle in the citric acid cycle doesn't need anymore acetyl coenzyme a and pyruvates ultimately are used to produce that acetyl coenzyme a and so what this tells us is a high amount of C of of acetyl coenzyme a basically means we don't want to produce anymore pyruvate molecules and so we can use the PI route molecules to form the glucose so this step will essentially increase in its rate now by the way anything in blue basically means it's an activator anything in red basically means it's an inhibitor now let's move on to this point here so what will happen here is the citric molecule which is an intermediate in the process of the citric acid cycle basically activates fructose 1 6 bisphosphate so again the citric MOT of the citrate molecule is essentially an agent that tells the cell that we have plenty of molecules to actually go around to use in the citric acid cycle and so we don't want to produce any more intermediates in the citric acid cycle and so we don't want to produce any more pyruvate and that implies that pyruvate can now be used to form the glucose which in turn can be used to actually replenish our glycogen stores in the cells of our body so these two enzymes are essentially activated and that allows this process of gluconeogenesis to actually take place at the same exact moment in time when we have a high energy charge value lots of ATP relative to a MP then this process will be turned off how will it be turned off so let's begin in this stage here so stage number one by the way is the inter conversion of fructose 1 6 phosphate and fructose 1 6 bisphosphate and the enzyme that catalyzes this step in glycolysis is phosphofructokinase now phosphofructokinase as we discuss previously is inhibited by large amounts of ATP and so ATP will bind unto an allosteric site of phosphofructokinase inhibiting its activity at the same exact time if this is inhibited then the phosphofructokinase 6 phosphate cannot be transformed into fructose 1 6 bisphosphate and so this concentration will build up now as this concentration builds up because these two molecules are essentially at equilibrium not exactly but they're pretty much at equilibrium then as we build up this concentration that causes a buildup in the glucose 6-phosphate and as this builds up the glucose 6-phosphate g6p where this is g6 and Pia basically goes on to inactivate hexokinase so by inactivating phosphofructokinase we also in activate the hexokinase by the pathway that i just discussed now let's discuss H+ ions and citrate now in skeletal muscle cells when the rate of glycolysis will exceed the rate of oxidative phosphorylation that takes place in the mitochondria there will be a buildup of lactic acid so as a result of lactic acid fermentation and so we will increase the H+ ions and that will also inhibit the activity of phosphofructokinase now I put a star next to this because this is not true for liver cells because in liver cells the H+ ions don't really affect phosphofructokinase and that's because in the liver cells they have the ability to actually transform lactate into pyruvate and so the H+ ions don't affect the phosphofructokinase is found inside the liver cells but the citric molecules do affect phosphofructokinase in liver cells so in liver cells we have the citrate basically goes on to bind onto phosphofructokinase to basically tell that molecule to stop the process of glycolysis why well because if we have plenty of ATP molecules that also means we have plenty of pyruvate molecules and pyruvate under aerobic conditions ultimately goes on to the citric acid cycle to form citrate so if we have lots of citrate molecules we don't want to form any more pyruvates and so that goes on to phosphofructokinase in activating inhibiting the phosphofructokinase now let's move on to pyruvate kinase so this molecule is the enzyme that catalyze the final step in glycolysis in the same way that ATP inhibits phosphofructokinase ATP also inhibits pyruvate kinase but in addition because pyruvate as we'll see in a future lecture is actually used to form alanine if we have plenty of ATP that means we have plenty of pyruvate molecules and so we have plenty of alanine molecules and the alanine the increase in alanine will basically go back and create a negative feedback loop that will inhibit the action of pyruvate kinase now in liver cells unlike skeletal muscle cells in liver cells the pyruvate kinase exists in the LI design form and the LI design form of liver cells is also affected by phosphorylation so in liver cells not in skeletal muscle cells that pyruvate kinase can also be inhibited by the process of the sporulation and so I put a star here because this is only true for liver cells it's not really true for skeletal muscle cells in the same exact way this citrate only inhibits the phosphofructokinase in liver cells and the h plus only really inhibits the phosphofructokinase in skeletal muscle cell so we see that when we have plenty of ATP molecules inside ourselves we don't want to form anymore ATP molecules in fact we want to use up some of those ATP molecules to replenish our glycogen stores and so glue glycolysis is turned off but gluconeogenesis is turned on so that we can use things like amino acids and glycerol molecules and lactate molecules to form the glucose from the pyruvate and then we can take the glucose and transform it into the glycogen molecule to basically replenish our storage of glycogen so when the cell has a high ATP concentration relative to A&P this tells the cell to start producing ATP via glycolysis and begin generating glucose via glucan Genisys to store it as glycogen and under these conditions glycolysis is halted and gluconeogenesis is activated and so we basically describe the same exact things I described just a moment ago so in the case of glycolysis we have phosphofructokinase is inhibited by ATP in skeletal muscles by H+ and liver cells by citrate the hexa kinase is in turn inactivated by this buildup of the glucose 6-phosphate and pyruvate kinase is inhibited by ATP alanine and in liver cells by the process up is for elation at the same time this is activated as a result of the activation of fructose 1 6 bisphosphate by the citrate molecule that we basically discussed here and the pyruvate carboxylase the first step of this gluconeogenic pathway it is activated by acetyl coenzyme a now let's switch our discussion to supposing that we have a low concentration of ATP in our cells so if we have low amounts of ATP relative to a MP what that means is our energy charge of the cell will be low and under these conditions we want to be able to generate a net amount of ATP we don't want to use up ATP and so in this case glycolysis will essentially be activated while gluconeogenesis will be inhibited now how is this actually regulated well once again let's suppose let's begin with gluconeogenesis and let's see how gluconeogenesis is actually in activated when we have little ATP in our cells so let's begin at this stage in this stage here so essentially stage number 2 so we have adenosine diphosphate inhibits not only pyruvate carboxylase but also the pep carboxylase remember pep carboxylase transforms oxaloacetate into phosphoenolpyruvate now because we have essentially lots of a and p in our cell the A&P goes on to bind onto the fructose 1 6 bisphosphate ace and that in activates this step here not only that but fructose 2 6 bisphosphate also in activates fructose 1 6 bisphosphate now don't worry too much about this molecule here the F 2 6 BP we're going to focus on that much more in the next lecture when we discuss how glucose levels in the blood actually activate or enact debate these two processes now what happens on this end so this in activates a gluconeogenic process but

Channel: Andrey K

Views: 179,324

Keywords: regulation of gluconeogenesis, reciprocal regulation of gluconeogenesis, control of gluconeogenesis, glycolysis and gluconeogenesis regulation, regulation of glycolysis and gluconeogenesis, glycolysis, gluconeogenesis, biochemistry, part I, energy charge

Id: ardjd4h2Seo

Length: 16min 8sec (968 seconds)

Published: Thu May 21 2015