Gluconeogenesis Pathway Overview Enzymes. the parthenogenesis pathway is responsible for the generation of glucose from non-carbohydrate sources. The first step in gluconeogenesis is the conversion of pyruvate to glucose by the Pyruvate Kinase enzyme. Gluconeogenic enzymes also catalyze the transfer of electrons from pyruvate to oxaloacetate, which then produces acetyl CoA.
Gluconeogenesis is the process of producing glucose from non-carbohydrate substrates in the body. Gluconeogenesis takes place in two primary pathways: the Pyruvate Carboxylase-Embden-Meyerhof (PCEM) pathway and the Phosphoenolpyruvate Carboxylase (PPC) pathway. The PCEM pathway uses pyruvate as the substrate and produces glucose and carbon dioxide.
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Hey, everyone, in this session, we’re going to talk about gluconeogenesis. So we’re first going to get into what gluconeogenesis is, how it functions, what are the important enzymes in gluconeogenesis? And we’re also going to talk about some of the substrates that can be used in glucoseogenesis. So to begin, what is gluconeogenesis? Well, gluconeogenesis is the synthesis of glucose from non carbohydrate precursors.
Gluconeogenesis Pathway Overview Enzymes
Gluconeogenesis is the process of synthesizing glucose from non-carbohydrate sources. Gluconeogenesis occurs in the liver and muscles, and can be stimulated by fasting, exercise, or a high carbohydrate diet. There are two main pathways for gluconeogenesis: the glycolysis pathway and the pentose phosphate pathway.
So that is the very important part of this definition. It is synthesis of glucose from noncarbohydrate precursors. So just remember that. So why is gluconeogenesis important? Well, it’s very important during fasting and starvation, and it’s because it actually maintains blood glucose levels and concentrations.
Now why do we need to maintain blood glucose levels and concentrations? Well, it’s because the brain and our red blood cells, or Erythrocytes, are actually heavily reliant on glucose. Now, gluconeogenesis actually primarily occurs within the liver and can actually occur secondarily, as I like to say, within the kidney. And this will actually occur during chronic or prolonged fasting as well as liver failure. Now here is the glycolysis pathway laid out, and it’s important to realize that many parts of the gluconeogenesis pathway are simply reversal steps of the glycolysis pathway, but it is not equivalent to simply a reversal of the glycolysis pathway.
And it’s because if you remember in my glycolysis video lesson that there are three important irreversible steps within the glycolysis pathway, and those steps are glucose conversion into glucosex phosphate by the enzyme hexokinase, the fructose phosphate conversion into fructose one, six bisphosphate by phosphofryptokinase one, or PFK one. And then the last step in the pathway is irreversible step, and that is the conversion of fossilinal pyruvate, or Pep, to pyruvate by the enzyme pyruvate kinase.
So when we’re trying to reverse the pathway from pyruvate back up to glucose, we need to go around these three enzymes. Now, that is the crux of the gluconeogenesis pathway, and the beginning of the pathway is simply the end of the glycolysis pathway, and that is pyruvate. Now, in order to go around the enzyme pyruvate kinase, pyruvate has to go through the enzyme pyruvate carboxylase to form oxalo acidate.
Now, it’s important to realize that pyruvate carboxylase is actually located in the mitochondria. Now, oxalo acidate will also have to be converted using a different enzyme into phospholino pyruvate by the enzyme Pep carboxy kinase. Now to get into a little bit more specific details, I mentioned before that pyruvate carboxy is within the mitochondria. Now, that means that pyruvate has to enter the mitochondria to actually be processed by that enzyme. Now how does it do that?
Gluconeogenesis pathway SlideShare
Well, the first thing that has to be done is that pyruvate has to be translocated into the mitochondria, and it’s transported into the mitochondria by the transporter mitochondrial pyruvate carrier, or MPC. Once pyruvate is within the mitochondria, pyruvate will be processed by pyruvate carboxylase into oxalic acetate.
Now, this enzyme, again, is within the mitochondria. It requires ATP for its function, and it also requires or is activated by acidl COA, which means that during times of increased amount of acetylcoae, Pyruvate carboxylase will actually become activated and will actually process Pyruvate into oxalacetade. Now, another important point to clarify with this enzyme is that this enzyme actually requires biotin or vitamin B seven for its function.
So once we have Oxaloacetate, Oxaloacetate can be processed by the enzyme Malate dehydrogenase to form Malate. Now, as you can see, I have a double arrow for Malat dehydrogenase, which means that this is a reversible process this is a reversible enzyme which means that Oxalaseate can be converted to Mallet and Mallet can be converted back to oxalic acidate. Now, an important cofactor for this enzyme is NADH and NAD plus. So in the processing of Oxalo acidate into Malate, NADH will actually be processed and utilized to form NAD plus in the reversal of that enzyme from Mallet to Oxalo acidate. It is the opposite from NAD plus to NADH.
gluconeogenesis pathway diagram
Really giving a lot of emphasis on this is that within the mitochondria we have higher levels of NADH. There’s actually higher levels of NADH in the mitochondria, which means that the reaction from oxalic acetate to Malate is actually more favorable. It is more likely that oxalicate will be converted to Malate than the opposite direction once we have Malate. Why does oxalicate acetate get converted to Malate? I didn’t show you that in the previous pathway, but the reason that oxalacetate is converted to Malate is because oxaloacetate cannot exit the mitochondria.
It cannot penetrate the mitochondria membrane, but Malate can because there is an actual transporter within the membrane and that transporter is the Malate aspartate shuttle. Malate can exit the mitochondria into the cytosol in exchange for an aspirate. Now, once Malate is into the cytosol, Mallet can actually undergo the same processing by Malle dehydrogenase back into oxalace. The reason is because there’s actually more NAD plus within the cytosol. Then there is NADH.
So it’s the opposite. It is more favorable for the reaction to proceed from Malate to oxalo acid in the cytosol because there’s actually higher levels of NAD plus. Now, once Malate is converted to oxaloastate in the cytosol, oxalacate can actually then be processed by the enzyme phospholino pyruvate carboxy kinase. And this releases a CO2 molecule. And this enzyme requires a GTP for its function.
gluconeogenesis pathway diagram
So we end up having phospholino pyruvate at the end. So now, going back to this pathway again, we see that these two steps requires the equivalent of about two ATP. Now, as we go up backwards in the pathway from fossilinopyruvate to two fossil glycerol to three fossil glycerol back into one three bit fossil glycerite.
There’s actually an important step here as well that I want to mention. So in the reversal conversion of three fossil glycerite to one three bisphosphalycerate, we have to go where we have to use the enzyme phosphoglycerate kinase, which actually costs another ATP.
Gluconeogenesis Pathway Overview Enzymes Once we have one three bisphosphoglycerade, this can be converted back to glycerolde three phosphate, which then can be converted to Fructose one six bisphosphate, which then can be converted back to fructose six phosphate by the enzyme fructose bisphosphate. And then fructosex phosphate can be converted to glucose phosphate. And then glucosex phosphate can be converted back into glucose by the enzyme glucose six phosphatease.
So just remember that the phosphateases are the enzymes required for these reversal steps in gluconeogenesis. So before I move on, it’s important to realize that the total amount of ATP used in these steps in the glucose neogenesis pathway is actually twice the amount of ATP, because what we do is there’s actually two ATP used for the pyruvate carboxylase and Pep carboxy kinase steps, and there’s another one for phospholus kinase, but that is only for one piece of the Fructose one six bisphosate.
Remember, we have to have two three carbon molecules that combine to form Fructose one six bisphosphate. So it actually costs two times the amount that we show. So, actually, the Gluconeogenesis pathway actually costs six ATP to go from Pyruvate all the way back up to Fructose one six bisphos. It actually costs six ATP in total.
Regulation of gluconeogenesis
Gluconeogenesis Pathway Overview Enzymes So to get into more detail about how Fructose one six bisphosphate is processed into Fructose six phosphate, we remember that I mentioned before it’s processed by the enzyme Fructose bisphostates and in doing so, Fructose one six bisphosphate gets converted to Fructoseix phosphate and it actually releases one inorganic phosphate and this step actually does not cost any ATP does not cost any energy.
Now, this is an important enzyme because it’s actually regulated and it’s regulated by things such as Glucagon Glucagon actually activates Fructose bisphosphatease and it’s actually activated by citrate and this enzyme is inhibited by amp and inhibited by Fructose 26 bisphosate. So you might not remember where Fructose 26 bisphosate actually comes from but it actually comes from the conversion of Fructosex phosphate by the enzyme phosphorfractokinase two or PFK two. And remember in the Glycolysis pathway, it’s actually PFK one that produces fructose.
