Now, we can say that gluconeogenesis is a sequence of 11 biochemical reactions with 2 pyruvates as our starting metabolites. We're going to say here that reactions 1, 2, 9, and 11 are different from glycolysis with the rest being the same. If we take a look here, on top we have gluconeogenesis. And with gluconeogenesis, our goal is to go from pyruvate to glucose. And for glycolysis on the bottom, we start with glucose and our goal is to get to pyruvate. So they're going in opposite directions, they are similar in many parts, but again it's reactions 1, 2, 9, and 11 that are different. If we go back up to gluconeogenesis, we have pyruvate. Reaction 1 will transform that into Oxaloacetate. Going into reaction 2, we make PEP, which is Phosphoenolpyruvate. And then we're going to have our reversible reactions, 3 to 8, which transform it into Fructose 1,6-bisphosphate. Reaction 9 changes that into just Fructose 6-phosphate and then reaction 10 which is reversible, gives us glucose 6-phosphate, so that in reaction 11 we finally get glucose. Glycolysis will go the opposite way, we're starting out with glucose, step 1 gives us glucose 6-phosphate, step 2 is reversible and gives us Fructose 6-phosphate, step 3 here would change that into Fructose 1,6-bisphosphate, and then steps 4 to 9 are reversible, we can go from Fructose 1,6-bisphosphate to PEP again. And then step 10 will go straight into Pyruvate. We'll go deeper into looking at gluconeogenesis, but just remember it's a total of 11 biochemical steps or reactions. And we're going to say here it's reactions 1, 2, 9, and 11 that are different from glycolysis with the rest being the same.
Gluconeogenesis - Video Tutorials & Practice Problems
Gluconeogenesis Concept 1
Video transcript
Gluconeogenesis Concept 2
Video transcript
Now, reaction 1 of gluconeogenesis deals with oxaloacetate formation. Remember we are dealing with 2 pyruvates, so this happens twice. In it, carbon dioxide is added to pyruvate by pyruvate carboxylase. So remember, we're adding CO2 group carbon dioxide and because of this, we have to use a carboxylate enzyme. And, this is going to produce oxaloacetate. In this, ATP is converted to ADP. So energy is invested into this. And what we need to note here is that amino acids can enter either as pyruvate or oxaloacetate. Here, if we take a look, we have our pyruvate here. We're going to add our carbon dioxide. We utilize ATP. In the process, ATP is converted into ADP. We utilize our enzyme pyruvic carboxylase and we add COO- in order to create oxaloacetate. So this represents reaction 1 of gluconeogenesis.
Gluconeogenesis Concept 3
Video transcript
Now, in reaction 2 we have our 2 oxaloacetates. In this step, we have decarboxylation, which means that we're going to lose Carbon Dioxide, and we have phosphorylation, which means we're going to add an inorganic phosphate group. Here, we're going to use PEP, we’re going to say carboxykinase. Remember, a kinase is the class of enzymes we use for the transferring of a phosphate group to our specified molecule or the removal of a phosphate group in some instances. Now here, it's going to remove CO2 in order to add our inorganic phosphate group. In this reaction, we have GTP is converted to GDP and one carbon atom is lost as carbon dioxide. So, here we have our oxaloacetate, we're utilizing our GTP which loses the inorganic phosphate group to become GDP. In the process, we're losing carbon dioxide so that's the decarboxylation step. The enzyme that we utilized here is phosphophenolpyruvate which is PEP, and then carboxykinase. Here we include our phosphate group as PO43-. So, that's how we go from oxaloacetate to phosphoenolpyruvate or PEP.
Gluconeogenesis Example 1
Video transcript
In this example, it says, how many total carbon atoms are lost in the first two reactions of gluconeogenesis? Now remember, in reaction 1, we're dealing with a carboxylation reaction; we're adding a carbon dioxide molecule. In reaction 2, we have decarboxylation that occurs as well as phosphorylation, but we're focusing on the carbon atom. We have decarboxylation when we lose a carbon dioxide. So what is the net change? We added 1 in reaction 1, we lost 1 in reaction 2, so overall, it's a wash. So we're going to say a total of 0 net carbons are lost in the process. Alright. So here, the answer would be option A.
Gluconeogenesis Concept 4
Video transcript
In reaction 3 of gluconeogenesis, we have hydration. Again, we have 2 molecules or 2 metabolites involved, so this happens twice. Here we have PEP undergoes hydration to produce 2 PG, which is 2-phosphoglycerate. Now, here in order to do this, it's catalyzed by the enzyme enolase. Enolase is just a class of lyases. Remember, the way lyases work is they catalyze reactions in which things are added to double bonds or pi bonds. If we take a look here, we have PEP, which is phosphoenolpyruvate. We have the presence of a pi bond because of the presence of that double bond. We're going to say here, through the use of our enolase, water comes in and hydration just means the addition of water. In this, we have water which is basically H+ OH-; the H adds to the carbon that possesses the inorganic phosphate, and then the OH will attach to this CH2 on the bottom. And by doing this, we create 2-phosphoglycerate as our product for reaction 3 of gluconeogenesis. So, just remember, we're undergoing hydration. In order to do this, we use a class, a specific class of lyases called the enolase enzyme. Right, so we're going to add water to our pi bond, thereby breaking it and creating alcohol as our product.
Gluconeogenesis Concept 5
Video transcript
In reaction 4 of gluconeogenesis, we're starting out with 2 Pg's. And 2 Pg is 2 phosphoglycerate. And we're going to say here that our 2 PG molecules, they're going to undergo isomerization and they're going to yield 3 PG or 3 phosphoglycerate. And we're going to say here, this is catalyzed by the enzyme phosphoglycerate mutase. Mutase belongs to the class of enzymes called our isomerases. So basically, these two structures, they have the same molecular formula but different connections. They are isomers of one another. If we take a look here we have 2 phosphoglycerate, the inorganic phosphate is on carbon number 2 of our structure. Through the utilization of our phosphoglycerate mutase, we can have it migrate to position 3 of this chain. And in that way, we go from 2 phosphoglycerate to 3 phosphoglycerate. So, here basically, this OH now is located here and the inorganic phosphate itself moved to position 3. And that's how we're able to go between these two different types of glycerate molecules.
Gluconeogenesis Concept 6
Video transcript
Reaction 5 of gluconeogenesis involves a phosphate transfer. Remember, the class of enzymes that we utilize when it comes to the transferring of a phosphate group are the kinases. Now, here we're going to say that 3-PG, which is 3-phosphoglycerate, produces 1,3-bisphosphoglycerate by adding or gaining an inorganic phosphate group. Here we're going to say that it's catalyzed by our phosphoglycerate kinase. Kinase is the class of enzymes we use for phosphate transfers. Now, what happens here is that we have ATP and it's converted to ADP. If we take a look at our reaction, we have our 3-phosphoglycerate, the inorganic phosphate is on carbon 3. We're going to say our phosphoglycerate kinase, it's going to remove an inorganic phosphate group from ATP, transforming it into ADP. What's going to happen here is that this oxygen here, that's on carbon number 1, will gain an inorganic phosphate. Doing this creates 1,3-bisphosphoglycerate as our new product. So, just remember when it comes to reaction 5 of gluconeogenesis, it is a phosphate transfer, the class of enzyme we use to transfer phosphate groups from one molecule to a new specified molecule is a kinase.
Gluconeogenesis Concept 7
Video transcript
Now, reaction 6 of gluconeogenesis is a reduction. Here we're going to say that 1,3-bisphosphoglycerate undergoes reduction to produce G3P, which is Glyceraldehyde 3-Phosphate. Now, we're gonna say it's catalyzed by the enzyme Glyceraldehyde 3-Phosphate or G3P dehydrogenase. Remember, our dehydrogenases are enzymes of choice when dealing with redox reactions. We're dealing with reduction here so we can utilize it. Now, here we're gonna say in this process where we have reduction being undergone, we're gonna say NADH is oxidized to NAD+. If we take a look here, we have our 1,3-bisphosphoglycerate, we have our 2 inorganic phosphates, one on carbon 2 and one on carbon 3. We're gonna say, NADH is oxidized to produce NAD+. Here, we're also going to have an inorganic phosphate group. And through the use of dehydrogenase, this phosphate group that is lost is replaced by a hydrogen. So, we just created a carbon-hydrogen bond by removing a carbon-oxygen bond. This is where reduction occurs. Remember, reduction is either the loss of oxygen or the gaining of hydrogen. So here we can see that carbon lost an oxygen and it also gained a hydrogen, which represents a reduction reaction.
Gluconeogenesis Concept 8
Video transcript
Now, reaction 7 of gluconeogenesis deals with isomerization. In it, we have our G3P molecules which is Glyceraldehyde 3-Phosphate, they are isomerized to DHAP which is dihydroxyacetone phosphate. This is catalyzed by the enzyme Triose Phosphate Isomerase because it is an isomerization reaction. Note, we're going to say, glycerol enters gluconeogenesis as DHAP. Remember that our non-carbohydrates tend to go from their non-carbohydrate forms, we're talking about amino acids or lactate, they go into the pyruvate, and then they can go to DHAP and eventually they can go to pyruvate, to glucose. When it comes to glycerol, glycerol bypasses this and goes from glycerol straight to DHAP to eventually becoming glucose. Alright, so if we take a look here, we have Glyceraldehyde 3-Phosphate or G3P, we have our inorganic phosphate on carbon 3, position 3, utilizing our isomerase enzyme here, which is a reversible reaction. Here, we get to DHAP, which is our dihydroxyacetone phosphate. And remember, our glycerol, which is our 3 carbons with 3 OH groups, goes straight from this form into DHAP to eventually become glucose. Step 7 or reaction 7 of gluconeogenesis is an isomerization reaction.
Gluconeogenesis Concept 9
Video transcript
Now, reaction 8 of gluconeogenesis is a linkage reaction. Here our enzyme aldolase combines 2 triose phosphates into fructose 1,6-bisphosphate. Here we're going to have our DHAP, which is dihydroxyacetone phosphate, and it's going to combine with Glyceraldehyde 3-phosphate. Through the use of our aldolase enzyme, we get at the end our Fructose 1,6-bisphosphate. So again, think of this as the opposite type of reaction from glycolysis where we would have split fructose 1,6-bisphosphate into DHAP and G3P. Right. So here, now we're combining them together through the use of an enzyme of aldolase.
Gluconeogenesis Example 2
Video transcript
In this example question it says, "Which enzymes so far are involved in glycolysis but not gluconeogenesis?" So, at this point, we've gone over reactions 1 to 8. If we take a look at the first one, it says, pyruvate carboxylase. Now, this is the enzyme of choice that we use for reaction 1 in which we're going from pyruvate to oxaloacetate. This has been talked about as being involved in glycolysis and also gluconeogenesis. Next, we have phosphoglycerate kinase. Now, here, this is reaction 5 of gluconeogenesis, and remember, we're looking to see what's not part of gluconeogenesis. In reaction 5, this involves a phosphate transfer because we're using the class of enzymes known as a kinase. Now, options c and d. Now, d is actually reaction 6. We're going to say that it follows what we do in reaction 5. In this one, it's a reduction reaction because we're using Glyceraldehyde 3-phosphate dehydrogenase. Remember, this is involved in redox reactions, in this case, a reduction reaction. The answer here would have to be option c. This one is involved in glycolysis, but at this point hasn't been involved in gluconeogenesis. So option C would be our final answer.
Gluconeogenesis Concept 10
Video transcript
Now, in reaction 9 of gluconeogenesis, we have dephosphorylation, which means we're going to remove an inorganic phosphate. Here, the enzyme that we use is Fructose 1,6-bisphosphatase. A phosphatase is just the class of enzyme that's responsible for removing inorganic phosphate from a specified molecule. Now, here it removes the inorganic phosphate to form fructose 6-phosphate. If we take a look here, we have our fructose 1,6-bisphosphate, we have our 2 phosphate groups. Here, we're going to lose one of these inorganic phosphates through the use of the enzyme Fructose 1,6-bisphosphatase. Here, we keep intact this inorganic phosphate group, but the other one is lost, and now we have CH2OH here. In that way, we've just created fructose 6-phosphate as our new product for reaction 9 of gluconeogenesis.
Gluconeogenesis Example 3
Video transcript
In this example, it asks why it is not possible to dephosphorylate fructose 1,6-bisphosphate with the phosphofructokinase enzyme. Alright. So here, the phosphofructokinase enzyme does not function properly in the cytoplasm of the cell. That's not true. It can. Phosphofructokinase catalyzes the transfer of an inorganic phosphate group from one molecule to another, not the removal of an inorganic phosphate group. That is true. Remember, your class of enzymes known as kinases helps with phosphate transfers. We're taking our inorganic phosphate and moving it to another specified molecule. Here, that's not what's going on. Here, we're trying to completely remove the inorganic phosphate; we're not transferring it elsewhere. So, this is the answer. If we look at the other options, phosphofructokinase lacks enough energy to catalyze dephosphorylation. So, that's not true; it just transfers the phosphate group; it doesn't completely remove the phosphate group without transferring. And then here, we're going to say, no. In this case, we're attempting dephosphorylation to create fructose 6-phosphate. We're not transferring the phosphate group somewhere else. We're just completely removing it. So, this wouldn't answer the question correctly. So here, our answer would have to be option B.
Gluconeogenesis Concept 11
Video transcript
This video, we're going to take a look at reactions 10 and 11 of gluconeogenesis. Now, in reaction 10, we have isomerization. Here, our enzyme is phosphoglucoisomerase, which isomerizes fructose 6-phosphate into glucose 6-phosphate. Remember, these have the same molecular formula; they have different connections, so they're isomers of one another, which is why we would use an isomerase as our class of enzymes. So here, we're going from Fructose 6-Phosphate to Glucose 6-Phosphate utilizing this isomerase. Now here, the final reaction, reaction 11, is a dephosphorylation. Here, we're removing an inorganic phosphate. We're going to say the enzyme glucose 6-phosphatase removes an inorganic phosphate group, forming glucose. Now, the responsibility of a phosphatase enzyme is the removal of an inorganic phosphate from a specified molecule. This is different from a kinase. A kinase deals with a phosphate transfer, where we're removing an inorganic phosphate from one molecule and handing it over to another. That's not what's occurring here; we're just completely removing the inorganic phosphate. So here, we use our phosphatase to remove it completely, so now this becomes CH₂OH to help us form glucose as our final molecule within gluconeogenesis.
Gluconeogenesis Example 4
Video transcript
In this example question, it discusses steps 9 and 10 of gluconeogenesis. Now, remember, steps 9 and 10, or reactions 9 and 10, deal with dephosphorylations where we're removing an inorganic phosphate group. This process is accomplished through the use of a phosphatase enzyme. Remember, this is different from a kinase. A kinase deals with phosphate transfer. In these instances, we typically use ADP or ATP more, either removing or transferring these inorganic phosphate groups. Phosphatase, on the other hand, is just completely removing the inorganic phosphate group without transferring it to another molecule. In this context, it uses ADP to dephosphorylate and produces ATP. Here, if we're discussing this situation, we're talking about a kinase, not a phosphatase, so this is not true. It produces ATP as a result of dephosphorylation? No, we are not transferring an inorganic phosphate; we are not trying to take an inorganic phosphate from ADP and transferring it over to create ATP as a consequence. Requires GTP to dephosphorylate? The same kind of idea applies to GDP and ATP. The correct answer is (d). It does not require energy to dephosphorylate. Again, we are using a phosphatase enzyme, whose responsibility is just to remove the inorganic phosphate altogether. This process does not require the use of energy.
Gluconeogenesis Concept 12
Video transcript
Hey, everyone. So in this video, we're going to talk about our 3 memory tools to help us remember gluconeogenesis. These memory tools will help us to remember the reactions involved, our metabolites, as well as our enzymes. If we take a look at memory tool number 1, we're going to say this deals with our reactions. And it is, in the first two minutes of an accident, we have to call 911. Now, remember when it comes to gluconeogenesis versus glycolysis, gluconeogenesis is different at reactions 1, 2, 9, and 11 from glycolysis, with the rest being the same.
Next, we have memory tool 2 which deals with our metabolites. In this one we say that pirates only pop fruit from gorgeous gardens. Now, here what does this mean? Well, here PIRATES stands for our beginning metabolite of gluconeogenesis, which is pyruvate. O, deals with oxaloacetate. P is for PEP. Fruit, f here stands for Fructose 1,6-bisphosphate, f from 'from' stands for Fructose 6-Phosphate, gorgeous here is glucose 6-phosphate, and Gardens. What's the last that we want from gluconeogenesis? That's right, glucose. So here Gardens, g here stands for glucose.
Next, we have our enzymes from memory tool 3. And here we say that Pirates consume pepc k and we're gonna say fructose bis fizz, and then we're gonna say glucose fizz. Alright. So what does this mean? Well, here when we say pirates consume, we're talking about pyruvate carboxylase. This is what allows us to go from pyruvate to oxaloacetate. Next, we say PEP c k. Well, this is PEP carboxykinase. This will allow us to go from our oxaloacetate to just our Fructose 1,6-bisphosphate. Next, we have fructose bis fizz. This is fructose 1,6-bisphosphatase. Remember, a phosphatase is an enzyme whose role is just to completely remove our inorganic phosphate group. And then finally, we have glucose fizz. This would be glucose 6-phosphatase. Again, it's there just to remove an entire inorganic phosphate group. In this case, we're removing an inorganic phosphate group from glucose 6-phosphate in order to create glucose. Again, remember, gluconeogenesis, we're trying to create glucose that will be our end metabolite, and we're utilizing this last enzyme in order to do that. So just remember, rely on these three memory tools, help you get a full understanding of gluconeogenesis, where we first look at the different reactions involved that are different between gluconeogenesis and glycolysis. Next, looking at the metabolites as we go from one to the next to our eventual destination of the formation of glucose, and then our enzymes involved. The enzymes needed to go change one metabolite to another so that we get ultimately to glucose once again. Alright. So just keep this in mind when looking at gluconeogenesis.
Gluconeogenesis Concept 13
Video transcript
Now here when we take a look at a summary of gluconeogenesis, we're going to say gluconeogenesis reduces pyruvate to glucose via the following reaction: We have 2 pyruvate molecules, we're going to use 4 ATP, 2 GTP plus 2 NADH, and at the end, we get glucose.
Our 4th memory tool here is reaction 1, which deals with ATP, reaction 2, which deals with GTP, and reaction 5, which deals with ATP yet again. And it is all the pirates, so reaction 1, ATP. Reaction 2, GTP, got to party to reaction to, and then reaction 5 deals with ATP again at 5 PM. So reaction 5, 5 PM. Right? So this gives us a summary of what the overall reaction of gluconeogenesis is and memory tool 4 helps us to remember which reactions involve ATP and GTP respectively.
Gluconeogenesis Example 5
Video transcript
Here in this example question it says, reactions 1 and 2 consume blank and blank and are catalyzed by which enzymes. Alright. So remember memory tool 4. We're gonna say here that for reaction 1, it's ATP because remember, we're gonna say here all the pirates. So ATP. That means the answer is gonna be either a or b. Reaction 2 is GTP. All the pirates go to party. So GTP. So it's still either a or b.
Now, in reaction 1, we have oxaloacetate formation. Remember, that's us going from pyruvate to oxaloacetate. In order to do this, we need to add a carbon dioxide to pyruvate, and we'd say that if we're bringing in a carbon dioxide, that's going to require a carboxylase. So here pyruvate carboxylase. And then for reaction 2, we have a decarboxylation as well as a phosphorylation. Here we're going to have to lose a carbon dioxide from oxaloacetate and bring in an inorganic phosphate. Since we are basically transferring an inorganic phosphate from GTP to create our new structure which is PEP, we'd have to use a kinase enzyme. And here it would be a carboxykinase because we have CO2 being removed to usher in the inorganic phosphate group. So here, the answer would be b. Here, it would be pyruvate carboxylase and then basically, phosphoenolpyruvate (PEP) would be catalyzed by carboxykinase. So here, our answer would have to be option b.
The following metabolites are present both in glycolysis and gluconeogenesis, except:
oxaloacetate
fructose-1,6-bisphosphate
glyceraldehyde-3-phosphate
dihydroxyacetone phosphate
Which molecule is added to pyruvate and then removed in the next reaction?
H+
H2O
PO32-
CO2
Enzyme responsible for decarboxylation and phosphate transfer in the same gluconeogenic reaction is:
Tyrosine kinase
Oxaloacetate carboxykinase
Pyruvate kinase
Phosphoenolpyruvate carboxykinase
Phosphofructokinase
Fructose-1,6-bisphosphate is dephosphorylated by ________________ to fructose-6-phosphate.
Glucose-6-phophatase
Fructose-1,6-bisphosphatase
Phosphofructokinase
Fructose-6-phosphotase
Cori Cycle Concept 14
Video transcript
Now, the Cori cycle represents a cyclic metabolic pathway that transports lactate from muscle cells to liver cells and converts it to glucose. Recall that lactate is produced by muscle cells during anaerobic conditions, and it is then transported by the bloodstream to liver cells and converted to glucose through gluconeogenesis. If we take a look here, we have our muscle cell here, and our liver here. What happens is we're going to have the transporting of lactate from the muscle cells towards our liver. The lactate is then converted into pyruvate, and through the incorporation of energy in the form of ATP, we can transform that into glucose, being a result of gluconeogenesis. This glucose can then be shuttled off towards our muscles where it can be used. And here, we have glycolysis taking place which converts our glucose into pyruvate. Here we would have some of the releasing of ATP, remember in Phase B of glycolysis, this is the energy-forming phase of glycolysis, so ATP would be given off. And then remember in conditions of anaerobic conditions, we'd have fermentation going on where pyruvate wouldn't be able to go into stages 3 and 4 of food catabolism and instead would do fermentation. This would in turn create lactate and start the cycle all over again. So, basically what this is doing is it's taking something like lactate and converting it into something useful in the form of glucose, which our muscles can then use for energy. Right. So this is the beauty of the Cori cycle, which again is a cyclic metabolic pathway.
Cori Cycle Example 6
Video transcript
This example question asks, "The primary purpose for the Cori Cycle is to:" Alright. "Produce Lactate through the fermentation process." Lactate is something we don't really want to build up within our muscle cells. Okay. So here, this would make sense as a primary purpose for the Cori Cycle: "To provide a metabolite for gluconeogenesis." Alright. So here, the Cori Cycle, its primary focus, primary reason, and function is not to create a metabolite for gluconeogenesis.
Next, we're going to say "Generate glucose for muscle cells to use as an energy source." This is it. We're converting something that is not great for our muscle cells in the form of lactate and shuttling it off from the muscle cells to our liver to be converted into glucose through gluconeogenesis that can then be shuttled towards our muscles for energy. It helps provide an energy source for our muscle cells. So, this is the answer.
Here, "Provide liver with much-needed energy." Here it's just shuttling over the lactate to the liver cells; the liver itself is helping to convert that lactate into something useful in the form of glucose. So here, the best answer would have to be option C.
Which of the following statement(s) correctly describes the Cori cycle?
Lactate is converted back to pyruvate in the muscles.
Conversion of lactate to glucose in the liver generates ATP.
Glucose from muscle cells is transported to liver through bloodstream.
Lactate from the muscle cells is regenerated into glucose in the liver.
Both a & b.
a, c & d