Glycolysis: 3-PG –> 2-PG – Glycolysis and Pyruvate Metabolism

by Kevin Ahern, PhD

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    00:01 In the next reaction, 3-phosphoglycerate is converted into 2-phosphoglycerate by an enzyme known as phosphoglycerate mutase.

    00:09 And on the surface this looks like a very simple reaction but there is actually a lot of complexity to this.

    00:15 We are seeing the phosphate move from position 3 to position 2. However, this molecule has an intermediate that is created that is important to consider and this intermediate is something that has 2 phosphates. It's called 2,3-BPG.

    00:34 Now one of the important things about the 2,3-BPG is it's a molecule that has a very interesting affect on hemoglobin.

    00:41 Hemoglobin is the oxygen carrying protein in our blood and hemoglobin can bind to 2,3-BPG. And when it binds to 2,3-BPG, hemoglobin lets go its oxygen.

    00:54 Now that's important because where do we want hemoglobin letting go its oxygen. We want it to be like go at places where a lot of metabolism is going on because that's where the oxygen will be needed.

    01:07 And when glycolysis is going a lot one another things that it's making as a by product is 2,3-BPG.

    01:15 This is a good indicator to the body that "Hey here is where I need the oxygen" and hemoglobin is tuned to give it exactly.

    01:26 Now the delta G zero prime for this reaction is about 4.4 kJ/mol. It readily goes either direction as we have seen with some of the other reactions.

    01:34 Well 2,3-BPG is a pretty important molecule as you probably guess. So let's spend a little bit of time understanding how it is the cells make 2,3-BPG.

    01:44 There are actually two ways that cells can make this happen.

    01:46 One of these is by using an intermediate in the previous step of glycolysis.

    01:52 Now that intermediate was 1,3-BPG and in glycolysis you saw that it was converted to 3-phosphoglycerate and that generated a molecule of ATP.

    02:02 But 1,3-BPG can also be converted by an enzyme called bisphosphoglycerate mutase into 2,3-BPG.

    02:09 Now this is actually the most common way that cells will make 2,3-BPG and this enzyme is found in erythrocytes.

    02:18 Erythrocytes being blood cells and this helps blood cells to make 2,3-BPG to get rid of oxygen so that's very good.

    02:25 2,3-BPG can be converted back into 3-phosphoglecrate as you can see here, by the 2,3 bisphosphoglycerate phosphatase. Phosphatase is an enzyme that takes the phosphate off of something.

    02:37 So if that happens then what the cell has done is that little side steps around that substrate level phosphorylation in the last step of glycolysis.

    02:46 It doesn't affect our consideration of glycolysis, however.

    02:49 Now what I have been telling you though is that 3-phosphoglycerate can also make 2,3-bisphosphoglycerate and the way that that happen is through the unusual mechanism of action of phosphoglycerate mutase, the enzyme that catalyzes the conversion into 2-phosphoglycerate.

    03:07 Now so let's think about this. In the first reaction we saw two enzymes that had to convert first to the 2,3-biphosphoglycerate, and then back to the 3-phosphoglycerate.

    03:16 Now we see one enzyme that is making a by product that's 2,3-biphosphoglycerate.

    03:23 That's a little confusing. But let me tell you how the enzyme works and may be you will better understand how this all happens.

    03:30 In the enzymatic mechanism of going from 3-phosphoglycerate to 2-phosphoglycerate, one of the things that happens is the enzyme has the phosphate on position 3 and it wants to get the phosphate to position 2.

    03:43 Now you might logically think that the enzyme grabs the phosphate and it moves it up one.

    03:47 But that's not the way that a mutase works. A mutase, instead, starts with 3-phosphoglycerate, the phosphate on position 3, and it puts a phosphate on position 2.

    03:59 And then when it's done with that, it takes the phosphate away from position 3 and it's left behind with the phosphate on position 2.

    04:07 So you can see that in the intermediate phase the molecule has 2 phosphates on it.

    04:13 A phosphate on position 3 and a phosphate on position 2 that's how 2,3-bisphosphoglycerate is an intermediate in this pathway. Now 2,3-bisphosphoglycerate sometimes escapes the enzyme and that's how it gets out and goes and flags to the hemoglobin "Here is where the oxygen is needed," because of an accident in the process.

    04:35 If that accident doesn't happen then 2-phosphoglecrate is made and there is no 2,3-BPG.

    04:44 So the slower glycolysis is going, the less likely the accident will be to happen.

    04:52 In the next step of glycolysis, 2-phosphoglycerate is converted into phosphoenolpyruvate and the acronym for this one is pretty easy. This calls PEP.

    05:03 And you remember PEP because it has a lot of PEP.

    05:07 PEP is an intermediate that has a tremendous amount of energy as we shall see. It has a tremendous amount of PEP.

    05:14 Now the enzyme that catalyzes this reaction is known as enolase.

    05:18 And in this reaction what's happening is a water is being removed from 2-phosphoglycerate.

    05:23 That's what creates the double bond that we see in phosphoenolpyruvate and it's that double bond that helps give all the energy to this molecule.

    05:32 The delta G zero prime for this reaction is about 1, so it pretty much goes backwards and forwards without any significant difficulties.

    05:41 But PEP as we shall see is important for the last step of glycolysis.

    05:46 In the last step of glycolysis I'd like to call this reaction the big bang of glycolysis and there is a very good reason why. This reaction is another substrate level phosphorylation.

    05:59 We see that the PEP is converted into another 3 carbon molecule called pyruvate and in the process the phosphate is transferred from PEP onto ADP to make ATP. That means that PEP has to have a lot of energy to have that happen.

    06:13 We saw the same thing with 1,3-bisphosphoglycerate going to 3-phosphoglycerate.

    06:19 But what's different here? This substrate phosphorylation, what I call the big bang, this substrate level phosphorylation has a delta G zero prime of -31.7 kJ/mol.

    06:32 That's almost enough energy to make a second ATP.

    06:37 That's amazing. Well if we think about this "What happens to energy that we don't use?" "What happens when we have all this energy released?" Well one of the by products of inefficiency, whether that it's an automobile engine or it's a cell, one of the by products of inefficiency is heat.

    06:53 And heat is generated, the more we run this reaction, the more we get.

    07:00 So once you think about the last time you went jogging, and when you were out jogging, you got hot. Why did you get hot? Well you got hot because you had to run a lot of metabolic pathways and running those metabolic pathways, like this reaction, generates heat.

    07:14 Okay now this reaction because the delta G zero prime is so negative it's essentially irreversible.

    07:22 This means that if the cell is going to start with pyruvate and make glucose it actually has to do a little dance around this pathway, and we will see how that happens in pathway of gluconeogenesis.

    About the Lecture

    The lecture Glycolysis: 3-PG –> 2-PG – Glycolysis and Pyruvate Metabolism by Kevin Ahern, PhD is from the course Carbohydrate Metabolism.

    Included Quiz Questions

    1. It can be produced from 1,3-BPG and 3-phosphoglycerate.
    2. It is a glycolysis endproduct.
    3. It binds to myoglobin.
    4. It favors uptake of oxygen by oxygen-binding proteins.
    1. It is a very high-energy compound.
    2. It is made from 2-phosphoglycerate by addition of water.
    3. It is a stimulator of aldolase.
    4. It requires ATP to be produced.
    1. The reaction it catalyzes is readily reversible.
    2. It is both the last enzyme of glycolysis and a regulated enzyme of glycolysis.
    3. It catalyzes a substrate-level phosphorylation.
    4. The reaction it catalyzes releases a large amount of energy.
    1. 2,3-bisphosphoglycerate
    2. 1,3-bisphosphoglycerate
    3. 2-phosphoglycerate
    4. 3-phosphoglycerate
    5. Phosphoenolpyruvate

    Author of lecture Glycolysis: 3-PG –> 2-PG – Glycolysis and Pyruvate Metabolism

     Kevin Ahern, PhD

    Kevin Ahern, PhD

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    Thanks for pointing out other interesting details about this step, not always emphasized by other glycolysis overviews
    By Kelvin L. on 18. January 2021 for Glycolysis: 3-PG –> 2-PG – Glycolysis and Pyruvate Metabolism

    Dr. Ahern pointed out very interesting aspects like heat generation/high energy of PEP and the 2,3-BPG production. Maybe I wasn't paying attention the first time I learned about glycolysis, but this extra integrative information it makes this step easier to remember. Actually, in generally, these human focused biochemistry lectures, are easier to digest, since when I learned it originally, it was mixed with plant and microbial biochem.