Practice - Glycolysis 2: Videos & Practice Problems

The molecule 2-fluorot-2-deoxyglucose, used as an imaging agent, mimics glucose but has a radio-labeled fluorine at the C2 position. Cancer cells, with high glycolysis rates, trap this molecule, allowing for tumor detection via CT scans. In glycolysis, reactions 1, 3, and 10 are irreversible due to their negative ΔG, requiring new enzymes for gluconeogenesis. Phosphoglucoisomerase catalyzes the conversion of glucose 6-phosphate to fructose 6-phosphate, involving magnesium and rearranging the carbon structure.

Practice - Glycolysis 2

If you haven't done question 26 yet, pause the video now. The molecule 2-fluoro-2-deoxyglucose is used as an imaging agent to detect tumors, and the way this works is that cancer cells will actually have really high rates of glycolysis, and, in using this molecule, basically what we have is a molecule that looks just like glucose except the carbon 2 position is no longer bound to a hydroxyl group. Instead, it's bound to this radiolabeled fluorine right there, F18 or fluorine-18. So this radiolabeled fluorine is an atom that imaging technology like a CT scan can pick up on when you do a scan on someone. So, remember that when glucose enters the cell, the first thing that happens to it is hexokinase phosphorylates it, right? And that traps it in the cell, and it also, you know, tricks the concentration gradient for glucose to allow more glucose to enter the cell. In the case of this molecule, when it enters the cell, it's going to be converted into 6phosphoFHDG which is fluorodeoxyglucose, and basically, the idea is, this will trap it in the cell, meaning that cancerous cells which are going to have high rates of glycolysis are going to trap a lot of this molecule in the cell. They're going to sequester a lot of it, meaning they're going to have a very strong glow when a CT scan is performed because they're going to have a lot of that F18 in there. So, that is how this molecule is used as an imaging agent to detect tumors.

Now, in an anaerobic muscle preparation, lactate formed from glucose, with the C2 position labeled, would be labeled. So let's think about this. The answer is the alcohol carbon, but let's think about this. Here is pyruvate. And recall that this will be carbon 1 or 6 from glucose, this will be 2 or 5, and this will be 3 or 4. Now, in lactic acid fermentation, pyruvate is directly reduced by NADH, regenerating NAD⁺, and this forms lactate, and lactate looks like this: It looks just like pyruvate except we have reduced our ketone to an alcohol. So, the numbering is still the same. So here on the carbon attached to the alcohol is where carbon 2 from glucose would wind up. Now, glycerol is considered a non-fermentable sugar because it produces too much NADH to be efficient. It produces an extra NADH, over other 3-carbon molecules. Meaning that if you were to use glycerol and do fermentation, you would actually slowly be accumulating excess NADH. You would not be able to replenish your NAD⁺ at the same rate that you produce NADH because you would be producing too much NADH from glycerol. So, it is not considered a fermentable sugar. Meaning it's only going to be used in aerobic conditions when cellular respiration is going to occur because the NADH will be used up in electron transport then as opposed to just building up because we're relying on fermentation to replenish NAD⁺.

Now, while most reactions of glycolysis are easily reversible, reactions 1, 3, and 10 are irreversible and drive the pathway forward, and this is because they have a very negative delta G. Remember, these reactions are reactions of hexokinase, phosphofructokinase, and pyruvate kinase. And these two both cost ATP. And this reaction generates ATP. So, they're all very favorable reactions, meaning they're not easily reversible because they have a very negative delta G. And so when we do gluconeogenesis, these are the enzymes or the reactions that require new enzymes to go in the opposite direction.

Alright, last question. Phosphoglucoisomerase, also known as phosphohexoisomerase, the same enzyme, catalyzes the second reaction in glycolysis. Diagram the reaction in the glycolytic pathway and be sure to show all atoms of the substrate and product. Alright, I've drawn this in ahead of time. So, if you haven't drawn this out yet, pause the video now, draw it out, and I'm going to reveal the answer. I drew it in ahead of time just to save time. You don't need to watch me draw out this whole molecule, or both of these molecules. That is a waste of time. So, we start with glucose 6-phosphate. We need magnesium: our enzyme needs magnesium for this reaction and we wind up with fructose 6-phosphate. So, we do a rearrangement, and notice that here we have our carbon 2 and now here is our carbon 2. So, we have rearranged the ring in the course of this reaction.

Alright, let's flip the page.

Here’s what students ask on this topic:

What is the role of 2-fluoro-2-deoxyglucose in cancer detection?

2-Fluoro-2-deoxyglucose (FDG) is used as an imaging agent to detect tumors. It mimics glucose but has a radio-labeled fluorine atom at the C2 position. Cancer cells, which have high rates of glycolysis, uptake and trap FDG in the form of 6-phospho-FDG. This accumulation can be detected using imaging technologies like CT scans, as the radio-labeled fluorine emits signals that highlight areas of high glycolytic activity, indicating potential tumor sites.

Why are reactions 1, 3, and 10 of glycolysis considered irreversible?

Reactions 1, 3, and 10 of glycolysis are considered irreversible because they have a very negative ΔG, making them highly exergonic. These reactions are catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase, respectively. The negative ΔG ensures that these steps drive the pathway forward and are not easily reversible. During gluconeogenesis, different enzymes are required to bypass these irreversible steps.

How does phosphoglucoisomerase function in glycolysis?

Phosphoglucoisomerase, also known as phosphohexose isomerase, catalyzes the second reaction in glycolysis. It converts glucose 6-phosphate into fructose 6-phosphate. This reaction involves the rearrangement of the carbon structure and requires magnesium as a cofactor. The enzyme facilitates the isomerization by opening the glucose ring, rearranging the atoms, and then closing the ring to form fructose 6-phosphate.

Why is glycerol not considered a fermentable sugar?

Glycerol is not considered a fermentable sugar because it produces an excess amount of NADH compared to other 3-carbon molecules. During fermentation, the accumulation of NADH would outpace the regeneration of NAD+, leading to an imbalance. Therefore, glycerol is only used in aerobic conditions where the excess NADH can be utilized in the electron transport chain, preventing its buildup.

What happens to pyruvate during lactic acid fermentation?

During lactic acid fermentation, pyruvate is directly reduced by NADH to form lactate, regenerating NAD+ in the process. This reaction is crucial for maintaining glycolysis under anaerobic conditions. The carbon structure of pyruvate remains the same, but the ketone group is reduced to an alcohol group, resulting in the formation of lactate.