Glycolysis 2 - Online Tutor, Practice Problems & Exam Prep

Glycolysis involves a series of enzymatic reactions, starting with hexokinase, which phosphorylates glucose to form glucose 6-phosphate, committing to the pathway by expending ATP. The isomerization of glucose 6-phosphate to fructose 6-phosphate is reversible, facilitated by phosphohexose isomerase. Phosphofructokinase then phosphorylates fructose 6-phosphate, marking another commitment step. Aldolase splits fructose 1,6-bisphosphate into glyceraldehyde 3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP), with G3P continuing in glycolysis. Understanding these steps is crucial for grasping metabolic pathways and energy transfer in cells.

Glycolysis 2

As we move through the glycolytic reactions, the things that I want you to pay attention to are the name of the enzyme at each step which is going to be the first thing you see. The ΔG of that reaction which is going to tell you whether or not this is a readily reversible reaction, and the more negative the reaction, the less able to be reversed it is, or to put it in a less confusing way, if you have a ΔG that's close to 0, you have a readily reversible reaction. But the reactions you have, with your negative value, those are going to be what I'm going to call commitment steps because we're going to expend energy and commit to the pathway. So, you also lastly, want to pay attention to your reactants or substrates I should say, your substrates and your products. So, looking here, the first step of glycolysis is performed by hexokinase. That's our enzyme. We have a pretty negative value for ΔG, meaning this is not going to be readily reversible. That's why we have a one-way arrow here. And we're going to take glucose or hexokinase is going to take glucose I should say and it's going to turn it into glucose-6-phosphate. It's going to add a phosphate group onto glucose and this actually happens as soon as glucose enters the cell. As soon as glucose enters the cell, hexokinase performs this regardless of whether or not glucose is actually going to be broken down through. And you can see that we have to expend an ATP. And that ATP expenditure is going to allow us to attach that phosphate group onto glucose, and we're going to end up with ADP and a proton because we are breaking it, is going to leave ADP behind.

Moving on to the second reaction, the glycolytic pathway, we have phosphohexose isomerase and you can see here that the ΔG of this reaction is pretty close to 0, and that's why we have these both ways arrows, right? This means it's a readily reversible reaction. And that makes sense because this is an isomerase, right? We're not really doing a whole lot here. We're just rearranging the molecule a little bit. We're taking glucose-6-phosphate and we're turning it into fructose-6-phosphate. And you can basically see we're just changing the ring structure a little bit so that carbon-1 is no longer part of the ring. Now, the ring starts with carbon-2, right? We've moved from a 6-membered ring to a 5-membered ring.

Now, step number 3, carried out by phosphofructokinase. That's an enzyme name that you want to remember because it's going to come up many, many times even beyond this course probably. And phosphofructokinase, you can see, has a pretty negative ΔG. And we have a one-way arrow here, right? This is going to be our second commitment step. And we have to burn another ATP or expend another ATP, and we're going to do that and we're going to phosphorylate fructose-6-phosphate. So we're going to take fructose-6-phosphate from the previous reaction and we're going to add another phosphate group onto it. You can see it right there making it a bisphosphate, 2 phosphates. So, this is our second commitment step. This is going to be the last step of directly investing energy, but we're not quite at the energy payoff phase yet. So, remember, in terms of looking at glycolysis as a whole, we expend 2 ATP per glucose. So this is the second ATP we're expending.

Now, the 4th step of the reaction is performed by aldolase. Let me just hop out of the image here so you can see the whole thing. So, notice here, aldolase has a pretty high ΔG, right? So this is probably making you wonder how this reaction occurs at all. We'll notice that this is the ΔG prime naught there, right? Meaning this is a ΔG at standard biochemical conditions. But actually, in the cell at cellular conditions, the ΔG of this reaction is actually somewhere between negative 60. That's why this is going to be a readily reversible reaction. So don't be fooled by this ΔG of 23.8 because at cellular conditions, this is actually going to be more like -six or 0. And what we're going to be doing, we're going to be taking that fructose-1,6-bisphosphate. I've abbreviated it there to fit it all in one line, Great. So, that's this molecule right here. And we're going to actually split it up, right, aldolase. We're going to break up that aldol, and we're going to break it up into 2 molecules. One of which is glyceraldehyde-3-phosphate which I'm going to abbreviate G3P. You may have seen this molecule before. Some other, it's sometimes called PGAL which stands for phosphoglyceraldehyde. I personally prefer G3P, glyceraldehyde-3-phosphate. Or rather preferred G3P as my abbreviation because I think it's closer to the name glyceraldehyde-3-phosphate than PGAL. Doesn't really matter. We're going to call it G3P. End of story. Now, the other molecule that it gets broken up into is dihydroxyacetone phosphate or DHAP. So here we have G3P and this is DHAP. Now, G3P is ready to basically continue on in glycolysis. That's going to be the substrate of the next step. DHAP can't just jump into the next step though. DHAP actually has to be converted into G3P, which, I'm sure you can tell by looking at the structure, is not going to be the hardest chemical reaction to pull off as they're fairly similar molecules. So let's turn the page and take a look at what happens to DHAP.

Here’s what students ask on this topic:

What is the role of hexokinase in glycolysis?

Hexokinase is the enzyme that catalyzes the first step of glycolysis. It phosphorylates glucose to form glucose 6-phosphate, using one molecule of ATP in the process. This reaction has a highly negative ΔG, making it essentially irreversible and committing the glucose molecule to the glycolytic pathway. The phosphorylation of glucose also prevents it from diffusing out of the cell, thus trapping it inside for further metabolism.

Why is the reaction catalyzed by phosphohexose isomerase considered readily reversible?

The reaction catalyzed by phosphohexose isomerase, which converts glucose 6-phosphate to fructose 6-phosphate, has a ΔG close to zero. This indicates that the reaction is readily reversible under cellular conditions. The enzyme facilitates the isomerization by rearranging the molecular structure without significant energy changes, allowing the reaction to proceed in both directions depending on the cellular needs.

What is the significance of phosphofructokinase in glycolysis?

Phosphofructokinase (PFK) is a key regulatory enzyme in glycolysis, catalyzing the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate. This step is another commitment point in glycolysis, marked by a highly negative ΔG, making it essentially irreversible. PFK is allosterically regulated by various metabolites, making it a crucial control point for the glycolytic flux and overall cellular energy metabolism.

How does aldolase function in glycolysis?

Aldolase catalyzes the cleavage of fructose 1,6-bisphosphate into two three-carbon molecules: glyceraldehyde 3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP). Although the standard ΔG for this reaction is positive, under cellular conditions, the reaction is driven forward by the rapid consumption of G3P in subsequent steps. DHAP is then converted to G3P by triose phosphate isomerase, ensuring that both molecules can continue through the glycolytic pathway.

What happens to dihydroxyacetone phosphate (DHAP) in glycolysis?

Dihydroxyacetone phosphate (DHAP) is converted to glyceraldehyde 3-phosphate (G3P) by the enzyme triose phosphate isomerase. This conversion is necessary because only G3P can proceed to the subsequent steps of glycolysis. The isomerization of DHAP to G3P ensures that both molecules produced by the aldolase reaction can be utilized in the energy-yielding phase of glycolysis, thereby maximizing the efficiency of glucose metabolism.