A very good morning friends. Today we will discuss about an important topic in carbohydrate metabolism that is glycolysis. The another name for glycolysis is M. den Meyerhoff-Parnas pathway.
This is an important pathway because it occurs in both aerobic and anaerobic condition. We will discuss this pathway under the heading of important aspects of glycolysis followed by the steps in glycolysis then energetics and regulation With this we will discuss about the most common question in viva that is the difference between hexokinase and glucokinase and we will also discuss the action of fluoride ion on the enolase. So we will discuss this topic under this heading.
Coming to the important aspects of glycolysis. The first one is this pathway that is glycolysis or dissolution of sugar. It occurs in all cells of the body.
Then second, it occurs aerobically. and anaerobically. This is the important part of this pathway that is it operate in aerobic and anaerobic both conditions.
Number three It is an important source of energy for matured RBCs. Because matured RBCs does not have mitochondria. The oxidative phosphorylation will not occur in matured RBCs.
So it is completely dependent on the glycolytic pathway for energy. Then fourth, during the sternus exercise or vigorous exercise, This is the important pathway because there is demand of oxygen increases and as there is low supply of oxygen, this pathway operate anaerobically and provides energy to the muscle during the rapid exercise. then fifth the activity of this glycolytic pathway is low in cardiac muscles Because of this, whenever there is ischemic attack, it has very poor prognosis because of low activity of this glycolysis in cardiac muscles. Hence, energy cannot be provided by the anaerobic glycolysis. The next point is, It is responsible for generation of carbon skeleton of non-essential amino acids.
And also it is responsible for generation of glycerol part of fat. And the reversible states in glycolysis they are also involved in gluconeogenesis. Once again I repeat this pathway occurs in all cells of the body in cytoplasm.
Then it operates in aerobic and anaerobic condition. Provides energy to the matured RBCs and it is the only source of energy for matured RBCs. RBCs and during the sternus exercise the energy is provided by anaerobic glycolysis.
There is low activity of this glycolysis in cardiac muscles that that's why in case of ischemia and whenever or whenever there is myocardial infarction, it has poor prognosis. Then it is responsible for generation of non-essential amino acids and glycerol part of the fat. And the reversible steps in glycolysis are also involved in the gluconeogenesis. Now coming to the steps in the glycolysis. The first is the glucose.
This glucose is converted into glucose 6-phosphate by the phosphorylation. Then by isomerization this glucose 6-phosphate is converted into fructose 6-phosphate. And again by the phosphorylation this fructose 6-phosphate is converted into fructose 1,6-bisphosphate.
Now there is cleavage of this compound fructose 1,6-bisphosphate by the aldolase. and it gives dihydroxyacetone phosphate and glyceraldehyde 3-phosphate and these are the interconvertible compounds with the isomerization as DHAP is ultimately converted into glyceraldehyde 3-phosphate. Now this glyceraldehyde 3-phosphate is converted into 1,3-bisphosphoglycerate which is converted into 3-phosphoglycerate These three phosphoglycerate on isomerization with the mutase reaction it is converted into two phosphoglycerate which is converted into phosphoenolpyruvate and this phosphoenolpyruvate is converted into pyruvate. So these are the steps in aerobic lycolysis in which glucose is converted into the two molecules of pyruvate in aerobic condition.
While anaerobically this glucose is converted into pyruvate and then lactate. Okay. So this first phosphorylation reaction it is catalyzed by the hexokinase or glucokinase. We will discuss the difference between these two.
Then this reaction requires ATP. This reaction, this ATP is converted into ADP. There is isomerization reaction here. So phosphohexose isomerase brings about the conversion of this glucose 6 phosphate into the fructose 6 phosphate then again there is kinase reaction and this is a rate limited rate limiting and committed step in this pathway that is catalyzed by phosphofructokinase is this is the important step this first this is second and this is the third step these are irreversible steps in the tricholesis the first third and this conversion of phosphoenolpyruvate to pyruvate these are the irreversible steps rest of the steps are reversible Again here the one ATP molecule is utilized.
It is converted into ADP Then there is cleavage reaction by the action of aldolase This Fuctose 1,6-bisphosphate cleaved into the three carbon compound that is DHAP and glyceraldehyde 3-phosphate. There is isomerization reaction here with the help of phosphotriose isomerase. This DHAP is converted into glyceraldehyde 3-phosphate. Now from this glyceraldehyde 3-phosphate, there is generation of NADH.
from NAD with the help of glyceraldehyde 3-phosphate dehydrogenase. And this NADH in electron transport chain and oxidative phosphorylation, it gives 2.5 ATP. So one molecule of NADH gives 2.580p.
There is generation of two molecules of NADH. by this pathway that's why there is generation of 580ps into 2 that gives 580ps there are two important substrate level phosphorylation in this pathway this is the kinase reaction but it is a reversible reaction that is bisphosphoglycerate kinase that is bisphosphoglycerate glycerate kinase. This is a high energy compound.
There is substrate level phosphorylation here without undergoing the electron transport chain and oxidative phosphorylation. There is formation of ATP from ADP. So there is formation of ATP from ADP.
Then here is the mutase reaction. In which 3-phosphoglycerate is converted into 2-phosphoglycerate. And with the help of enolase. This 2-phosphoglycerate is converted into phosphoenolpyruvate. And this phosphoenolpyruvate with the help of pyruvate kinase.
That is. is converted into pyruvate. This is again a substrate level phosphorylation in which this high energy compound is responsible for generation of ATP without undergoing electron transport chain and oxidative phosphorylation. So here ATP production is there from ADP.
So coming to the important points in this pathway. There are three irreversible steps. The first one is the catalyzed by the hexokinase, glucokinase. Second one is catalyzed by the phosphopructokinase and third one is catalyzed by the pyruvate kinase.
So these are the three irreversible steps in this pathway. This step catalyzed by the phosphopructokinase, it is a rate limiting. rate limiting means This step decides the rate of this pathway.
This is a slowest reaction in this pathway and it decides the rate of this pathway. And second, this one is the committed step because it converts the fructose 6-phosphate into fructose 1,6-bisphosphate. And it has to undergo the complete glycolysis. There is no other fate of this fructose 1,6-bisphosphate.
So ultimately this phosphorructopinase decides the fate of the cell. of this pathway that's why it is a committed step. So this step the third step is important it is rate limiting and committed step in this pathway. The third irreversible step is catalyzed by the pyruvate kinase.
So there are two important substrate level phosphorylation here. The first one is the bisphosphoglycerate kinase. This is a kinase reaction.
reaction but it is a reversible reaction. Bisphosphoglycerate kinase there is production of ATP without undergoing electron transport chain and oxidative phosphorylation. Then second is the pyruvate kinase reaction. So these two are substrate level phosphorylation. These three are irreversible steps.
This is the first, this is the second and this is the third irreversible step in this pathway. So coming to the regulation of this pathway. In regulation these three enzymes are important. The first one is the hexokinase.
And glucokinase, hexokinase or glucokinase, this is the first. Second one is the phosphofructokinase, this one is the important. And third one is the pyruvate kinase.
So in regulation these three enzymes are important. Now coming to the hexokinase, glucokinase. This hexokinase, it is inhibited by glucose 6-phosphate.
Glucose 6-phosphate brings about the inhibition. In this glucokinase it is under control of insulin. activates the pathway while glucagon inhibits the pathway. Insulin favors the utilization of glucose. Means insulin promotes this pathway.
Then this phosphofructokinase This is an important rate limiting and committed step in this pathway. This phosphofructokinase, it is activated by insulin and inhibited by glucagon. Then there are two important MCQs. This one is the allosteric inducible enzyme.
As it is inducible enzyme it is induced by the insulin and repressed by the glucagon. Then it is activated by the AMP and fructose 2,6-bisphosphate. This is important for MCQ.
It is activated by AMP and fructose 2,6-bisphosphate. While it is inactivated by, allosterically inhibited by ATP and citrate. Then again Pyruvate Kinase, this Pyruvate Kinase it is activated by Insulin and deactivated or inhibited by the Glucaver. through the phosphorylation and dephosphorylation reaction.
So this is the regulation of this pathway by three important enzymes that is hexokinase, glucokinase, phosphopruptokinase and pyruvate kinase. Now coming to the energetics in the glycolysis. When this pathway operates aerobically in aerobic condition, There is generation of 7 ATP's. Means there is generation of 2 molecule of NADH which gives 5 ATP. And there is 2 substrate level phosphorylation.
So from the glucose we will get 2 molecule of glyceryl dihydrophosphate. And from 2 molecule of glyceryl dihydrophosphate we get 4 ATP's. 4 ATP's by substrate level phosphorylation and there is consumption of 2 ATP, one is here and one is here.
So minus 2 ATP. So total 7 ATP's are generated when pathway operates aerobically. While when there is anaerobic glycolysis there is generation of only two ATP's because this pyruvate is converted into lactate.
As this pyruvate it is converted into lactate with the help of lactate dehydrogenase. This NADH which is produced here, this NADH it is utilized here. So NADH here will be utilized and gives NAD. And again NAD will be utilized here.
So in this way, this NADH generated by this tape, it is utilized in the lactate dehydrogenase tape, while NADH generated in lactate dehydrogenase tape, it is utilized by the glyceryl dihydroxyphosphate dehydrogenase. So in this way, anaerobic glycolysis will occur. And in anaerobic condition, There is 4 ATP's from substrate level phosphorylation, substrate level minus 2 ATP's.
So that will give net 2 ATP. So aerobically it gives 7 ATP, anaerobically it gives 2 ATP. So this is all about steps. Regulation, important, committed and rate limiting steps, irreversible steps, two substrate level phosphorylation steps in this pathway. and energetics of this pathway along with the regulation mainly by the insulin and glucagon and this pathway is activated by allosterically, activated by EMT and fructose 2,6-bisphosphate and inhibited by ATP and