Regulation of Glycolysis in Liver Cells

previously we discussed how skeleton muscle cells of our body can actually regulate the process of glycolysis and in that discussion what we said was there are three major types of regulatory points in glycolysis and these three regulatory points are actually some of the enzymes that regulate that process so we have fossil fructose kinase hexokinase and pyruvate kinase so this is the enzyme that catalyzes step 3 this is the enzyme that catalyzes step 1 and this is the enzyme that catalyzes step 10 and the reason ourselves use these three enzymes is because these catalyze irreversible steps in glycolysis now phosphofructokinase as we said is the most important regulatory enzyme and that's because it catalyzes the irreversible commitment step so once the step actually takes place this fructose 1 6 bisphosphate that is transformed from fructose 6-phosphate by phosphofructokinase has to go on and complete the process of glycolysis now now we're going to talk about liver cells and before we actually begin let's compare the functionality of muscle cells and liver cells so skeletal muscle cells essentially have one function and that function is to allow us to actually move voluntarily so if I want to move my hand back and forth my skeletal muscle produces the ATP via glycolysis to allow that voluntary movement now what about liver cells well liver cells have a much more complex biochemical role and what that means is they not only use the glycolysis to produce ATP molecules that the liver cells actually need to survive but the liver also has to do things like maintain the glucose levels in our blood if the levels are too high up take that glucose and transform it into glycogen if the levels are too low break down that glycogen and release the glucose into our bloodstream so that the other cells of our body can essentially use that glucose to form eight P molecules and it has many many other roles for instance it uses the glycolysis process to basically synthesize building blocks like fatty acids as well as amino acids and so forth so the liver cells have many different types of functions and as a result it's no surprise that the way that our liver cells regulate the process of glycolysis is more complex than the way that our skeletal muscle cells regulate the process of glycolysis so in our discussion we're going to focus on liver cells and how liver cells regulate the process of glycolysis and although we'll see many similarities between skeletal muscle cells liver cells will see that liver cells use a slightly more complex regulatory pathway let's begin with phosphofructokinase so once again phosphofructokinase is the most important regulatory enzyme and what it does is it regulates that commitment step it transforms the fructose 6-phosphate into the fructose 1 6 bisphosphate which is committed to that step and this is our enzyme that catalyzes that step now let's remember how skeletal muscle cells actually regulate this enzyme so they use ATP and a and P molecules so let's suppose we have a high energy charge in the cell and what that means is we have a high ratio of ATP to a and P remember energy charge simply means the ratio of eighth ATP to a and P now if we're resting this is basically what we're going to have we're going to have too many ATP molecules and so what that means is we don't want to produce any more ATP molecules we have plenty of ATP molecules to go around and so phosphofructokinase will be inhibited by that large concentration of ATP and ATP acts as an allosteric inhibitor on the other hand if we don't have many ATP molecules in the cell then we have a low energy charge value so low ratio and we have many more MP molecules and they will bye until that phosphofructokinase and essentially activate them they will they will make them much more likely to actually convert the fructose 6-phosphate into the fructose 1 6 by phosphate bisphosphate so basically the takeaway lesson here is the same two allosteric molecules that are used by skeletal muscle cells to control phosphofructokinase is also used by liver cells but there are many important differences difference number one in skeletal muscle cells the pH actually effects the activity of phosphofructokinase so in our discussion previously we said that a low pH or a very acidic environment basically in activates inhibits phosphofructokinase in skeletal muscle cells and that's because in skeletal muscle cells as we exercise there can be a buildup in lactic acid but in liver cells there's usually no buildup in lactic acid and that's partly because the liver cells actually are responsible for breaking down that lactic acid into glucose molecules and that's exactly why the phosphofructokinase is not affected by the pH in liver cells now the second important difference is the molecule citrate so citrate as we'll see in just a moment just like ATP molecules is another example of an allosteric inhibitor to phosphofructokinase so let's suppose in our skeleton our liver cells we have a high oxygen content but we don't have many ATP molecules well if we don't have many ATP molecules then the glycolysis process will continue and will for many ATP molecules and also pyruvate molecules and because we're under aerobic conditions the Peru vade will essentially answer the mitochondria and carry out the citric acid cycle now one of the initial intermediates of the citric acid cycle is a molecule known as citric and citrate is ultimate from the pyruvate molecule that enters that mitochondria now eventually after we form any ATP molecules and the concentration of ATP Rises and the energy charge of the cell increases we will not want to form any more ATP molecules because what that will mean is not only what we have enough ATP molecules to go around we'll also have enough citrate molecules to actually create ATP molecules and so in this particular case if we have plenty of ATP molecules that means we'll have plenty of pyruvate molecules and plenty of citric molecules circling in that crep cycle and so if we have a high citrate and citrate concentration in the cytoplasm that citrate will go on and buy until phosphofructokinase and it will basically increase the ability of the ATP to actually inhibit the phosphofructokinase and so just like ATP citrate is also an allosteric inhibitor to the phosphofructokinase and this is the second important difference between the faster probe to kinase and skeletal muscle cells and the one in liver cells so we can summarize that in the following diagram so let's say the glucose enters the cell it's transformed into glucose 6-phosphate then it becomes fructose 6-phosphate and then the phosphor fruitcakes transforms it into the fructose one bisphosphate and now we have many steps to take place and ultimately we form that pyruvate molecule and in the presence of oxygen the pyruvate will enter the mitochondria and it will eventually form citrate intermediate molecules and so we and we also form ATP molecules after glycolysis and so if we essentially have many of these ATP molecules and citrate molecules they will create a negative feedback loop that will go back and bind onto the faster fruit so kinase and that will essentially diminished activity of that faucet fruit to kinase so if we have many ATP this will stop the process of glycolysis so that we don't over produce the ATP molecules now one of the functions of liver cells that I mentioned earlier is the fact that they are responsible for actually maintaining a concentration a normal concentration of glucose because if we have too many glucose in a blood that can be toxic to our body so let's suppose we just ingest a meal that is rich in carbohydrates and so the concentration of ATP in our blood essentially increases and it's the job of the liver cells to basically uptake all that glucose to bring the blood level glucose back to normal now what does this cell actually do with the glucose well it can form ATP molecules it can form many different types of building blocks it could form glycogen and what that means is in these situations the fossil fruit so kinase must be activated by some type of some type of powerful activator molecule to actually up take all those glucose molecules and convert those glucose molecules into these different types of things and so something that we don't find in skeletal muscle cells that we have in liver cells is this feedback known as feed-forward stimulation so let's take a look at the following diagram so let's suppose we ingest all these carbohydrates so in our blood we have a high level of glucose and what that means is these liver cells will begin to absorb those glucose and the glucose molecules will be transformed ultimately into fructose 6-phosphate now high levels of glucose means we'll have high levels of fructose 6-phosphate and when we have very high levels of fructose 6-phosphate in a cytoplasm some of them will begin transforming into a molecule known as fructose to 6 bisphosphate now fructose to 6 bisphosphate is a very potent very powerful activator of phosphofructokinase and what it allows the cells to do is it allows them to convert all these glucose molecules up take the glucose molecules from the blood bring that glucose level back to normal and essentially convert those glucose molecules into either ATP molecules or other types of molecules so we ultimately see there are two types of inhibitors and two types of activators so we have ATP molecules and citrate molecules that inhibit the phosphofructokinase but the AAP molecules and the fructose - 6 bisphosphate are actually activators of the fructose of the FASTA fructose kinase enzyme so once again when fructose 6-phosphate concentration is high some of it is transformed into fructose - 6 bisphosphate and this molecule is an allosteric activator of the enzyme it binds to that enzyme stimulates its activity and it continually carries out this process quickly and effectively now let's move on to hexo kinase so let's suppose inside our blood we have a high concentration of ATP inside ourselves we have a high concentration of ATP so we're essentially at rest and the high amount of ATP will begin to inhibit the phosphofructokinase now once phosphofructokinase is inhibited so this molecule is basically inhibited pfk is phosphofructokinase then we're going to see that there is a buildup of this substrate molecule there is a substrates of this enzyme fructose 6-phosphate so by the way this is step one of glycolysis step two of glycolysis and step three of glycolysis and once there is a buildup of this molecule because of the inhibition of this molecule by the ATP this molecule is in equilibrium with this molecule and so if we increase the concentration of this if there's a buildup of this biologically as principal it will shift this way and increase the concentration of glucose 6-phosphate now glucose 6-phosphate is the product molecule to this reaction so glucose is transformed by hexiciah knees in the first step of glycolysis to form glucose 6-phosphate and as we increase the concentration of glucose 6-phosphate due to the inhibition of pfk that increase in concentration will inhibit the hexokinase and this same exact right regulatory mode is actually used by skeleton muscles as well so just as in skeletal muscle cells glucose 6-phosphate is also an allosteric inhibitor to hexokinase and this is the process that allows the phosphofructokinase to actually communicate with the hexokinase and essentially tell it to turn off that first step in glycolysis and one thing and once these two irreversible steps are essentially turned off that greatly diminishes the rate at which the glycolytic pathway actually takes place now there is one important difference between hexokinase and liver cells and hexyl kindnesses in skeletal muscle cells in liver cells we have this same hexiciah neighs that we also have in muscle cells but in liver cells we have and a and important isozyme to this particular hexo kinase now let's recall what an isis EIN is so two protein molecules that are different are set to be isozymes if they essentially catalyze that that same similar type of process and the isozyme to the hexokinase that is found in liver cells but is not found in skeletal muscle cells is gluco kinase so unlike in skeletal muscle tissue there is an Isis on - hexiciah knees present liver cells known as Luca kinase now what is the major difference between glucokinase and hexa kindness while there are two important differences number one gluco kinase has a much lower affinity for that glucose substrate molecule then hexokinase in fact hexokinase is 50 times more likely to bind to the glucose substrate then than gluco kinase and that will create a very important difference as we'll see in just a moment the second important difference between hexokinase and glucokinase is that hexokinase is inhibited by glucose-6-phosphate when the concentration is high but gluco kinase is not affected is not inhibited by that glucose 6-phosphate so we see that unlike hexa kinase which is inhibited by high amounts of glucose 6 files

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Keywords: regulation of glycolysis, reguation of glycolytic pathway, regulation of glycolysis in liver, regulation of glycolysis in liver cells, regulation of glycolysis in cells, feedfoward stimulation, phosphofructokinase, hexokinase, pyruvate kinase, regulation of phosphofructokinase, regulation of PFK, citrate and ATP allosteric effects, energy charge of cell, fructose 2 6-bisphosphate, glucokinase, glucokinase in liver cells, isozymes, L-isozyme pyruvate kianse, biochemistry

Id: OG4A3Fkitvw

Length: 16min 5sec (965 seconds)

Published: Sun May 17 2015