 Dear students, so today we are going to see the pathway of the Gluconeogenesis. So if you are looking at this slide, you can see the over way of the glucose metabolism. So if you are carefully observing this pathway overall, you can see by means of this Gluconeogenesis process, pyruvate can be converted to glucose 6-phosphate and this glucose 6-phosphate can be converted back to glucose. In another way we can say that pyruvate can serve as a precursor molecule for the synthesis of glucose by the process called as Gluconeogenesis. So what is this Gluconeogenesis means? So it is the process which mainly synthesize glucose from non-carbohetric precursors. And some examples for this non-carbohetric precursors are, pyruvate is one good example. In addition to that some other precursors are lactate, then glycerol, amino acids, especially glucogenic amino acids. So these precursor molecules can lead into the synthesis of this glucose. So in other ways we can say that gluconeogenesis is the process whereby precursors such as lactate, pyruvate, glycerol and glucogenic amino acids they are converted to glucose. So we know that how this lactate is produced, how this pyruvate is produced, glycolysis can lead to the formation of this pyruvate similarly in anaerobic conditions, lactate can also be generated from this glycolytic pathway. And regarding this glycerol, the glycerol part of fat and similarly propionyl-CoA they are formed from out chain fatty acids, they are considered as minor sources of gluconeogenesis. And another important point regarding this gluconeogenesis is that it mainly occurs in the liver or the principal organ for gluconeogenesis process to carry out, it is this liver. And it is also said that perennial cortex also is able to synthesize glucose molecules but only 1.10 effective as compared to that of liver. And regarding the pathway, this pathway gluconeogenesis it is partly mitochondrial and partly acetylplasmic. And another peculiarity is that the gluconeogenesis it involves several enzymes of glycolysis but we cannot say that it is purely the complete reversal of glycolysis. It involves several enzymes of glycolysis but it is not a reversal of glycolysis. So the irreversible steps that are seen in glycolysis are circumvented by four enzymes and these four enzymes are considered as the key enzymes of gluconeogenesis. First of all we will be having a look into the pathway and it is also said that oxaloacetate is considered as a static material for this gluconeogenesis. So there are several sources for the production of this oxaloacetate and it is from this oxaloacetate glucose is synthesized through some other intermediates. Just having to look into this pathway here lactate can be converted to pyruvate, pyruvate is converted to oxaloacetate and it is this oxaloacetate which is converted to glucose by using this gluconeogenesis. So pyruvate gets converted to glucose through the intermediate oxaloacetate, lactate gets converted to glucose through the intermediate pyruvate and oxaloacetate. So these are all precursor molecules for the synthesis of glucose. So we will look into one important or the key gluconeogenic enzyme that is involved in the process of gluconeogenesis. We can call it as pyruvate carboxylase. The principal raw of this pyruvate carboxylase it is in the conversion of this pyruvate to oxaloacetate. It catalyzes the ATP-driven formation of oxaloacetate from pyruvate and carbon dioxide which is the form of bicarbonate ions and this produced oxaloacetate in the presence of another enzyme called as phosphoenolpyruvate carboxykinase. It is converted to phosphoenolpyruvate. This step utilizes one molecule of GTP and one molecule of GTP is released. So pyruvate carboxylase system this is considered as the first reaction. So here what happens is that this respective enzyme it catalyzes the conversion of this pyruvate to oxaloacetate. This ATP mitochondrial enzyme. Moreover it requires biotin as a cofactor. So pyruvate carboxylase it requires biotin as a cofactor for carrying its activity. And what happens after the formation of this phosphoenolpyruvate? So we have already said that majority of the enzymes involved in this gluconeogenesis they are quite similar to that of glycolysis. But we cannot say that it is not just the reversal of this glycolysis. Three steps are found to be different from that of this glycolysis. So we have already seen that pyruvate gets converted to oxaloacetate by pyruvate carboxylase and this oxaloacetate gets converted to phosphoenolpyruvate by the enzyme phosphoenolpyruvate carboxycanis. So after the formation of this phosphoenolpyruvate this phosphoenolpyruvate undergoes further reactions which are seen in the glycolytic pathway. Majority of the reactions they are all freely reversible. Until up to factors 1,6 bisphosphate these respective reactions can be reversed. Just have a look into the pathway that we have seen in the earlier class. You can see this phosphoenolpyruvate. Majority of the steps they are considered as the reversible steps. So here phosphoenolpyruvate is reversed back. It is reversed to form fructose 1,6 bisphosphate. So here there is one another important enzyme which converts this fructose 1,6 bisphosphate to fructose 6 bisphosphate. Here the enzyme involved is fructose 1,6 bisphosphatease. So fructose 1,6 bisphosphate is converted to fructose 6 bisphosphate by the enzyme. Fructose 1,6 bisphosphatease. In the next step the fructose 6 phosphate is isomerized to glucose 6 phosphate by the freely reversible reaction catalyzed by the respective isomerase that we have seen in the glycolytic pathway. And after the formation of this glucose 6 phosphate this glucose 6 phosphate is hydrolyzed to glucose. So there will be a subsequent removal of this inorganic phosphate. So glucose 6 phosphate is converted to glucose by the action of the enzyme glucose 6 phosphatease. So in other words we can say that the 4 gluconeogenic enzymes that are considered as key gluconeogenic enzymes are the first one is pyruvate carboxylase, the second one is phosphoenol pyruvate carboxykinase and the third one is fructose 1,6 bisphosphatease and the fourth one is glucose 6 phosphatease. So the first one pyruvate carboxylase it is concerned with the conversion of this pyruvate to oxalacetate. And phosphoenol pyruvate carboxykinase is concerned with the conversion of this phosphoenol which is coming from oxalacetate. And fructose 1,6 bisphosphatease is involved in the conversion of fructose 1,6 bisphosphate to fructose 6 phosphate and glucose 6 phosphatease is involved in the conversion of this glucose 6 phosphate to glucose. Now another one important point as we have earlier said that oxaloacetate is considered as one of the important precursor molecule for the synthesis of glucose. And we have also said that the reactions of the gluconeogenesis they are partly mitochondrial and partly they are cytoplasmic. So the first step of the reaction catalyst by the enzyme pyruvate carboxylase can lead into the formation of oxaloacetate. So this oxaloacetate it is in the mitochondrial part. This respective oxaloacetate which is in the mitochondria has to be transferred or transported to the cytoplasm. Then only the rest of the gluconeogenic reactions can carry out through the process of gluconeogenesis. And this transport of this oxaloacetate from the mitochondria to the cytoplasm is done by an important settling mechanism and we can call it as the malate aspartate shuttle. So it is this malate aspartate shuttle that transport the oxaloacetate synthesized in the mitochondria to the cytoplasm. And after when the respective oxaloacetate reaches the cytoplasm this oxaloacetate can lead into the formation of this glucose through the process of this gluconeogenesis. So malate shuttle is one important shuttle that is related to gluconeogenic pathway. It is meant for the transport of this oxaloacetate to cytoplasm. So now we will look into the energy requirement for carrying out this gluconeogenesis. So here when two molecules of this pyruvate is converted to oxaloacetate here two molecules of ATP is utilized. Similarly when two molecules of oxaloacetate is converted to phosphoenol pyruvate here also two GTPs utilized. When two molecules of three phosphoglycerate is converted to one three bisphosphoglycerate two molecules of three phosphoglycerate is converted to one three bisphosphoglycerate here also two molecules of ATP is utilized. So as a whole total the total energy required for carrying out this gluconeogenic pathway it is six molecules of ATP. So this is regarding the energy requirement of this gluconeogenesis. With this we conclude the topic on gluconeogenesis. In the next session I will come up with another topic. Thank you all.