Glycolysis 3 - Online Tutor, Practice Problems & Exam Prep

Understanding carbon numbering is crucial in glycolysis, particularly when converting dihydroxyacetone phosphate (DHAP) to glyceraldehyde-3-phosphate (G3P) via triosephosphate isomerase. This reaction is reversible with a delta G near 0. Each glucose molecule yields two G3P, leading to subsequent reactions like the formation of 1,3-bisphosphoglycerate and ATP through substrate-level phosphorylation. The process involves key enzymes such as glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase, emphasizing the importance of metabolic pathways in energy production and regulation.

Glycolysis 3

Before we move on to the fate of DHAP, I want to talk a little bit about carbon numbering because your professor likes to ask questions about it, and because there's a problem with the image we have here. Now, from the previous step, we were left with DHAP which we see here, and the carbon numbering is all fine on this, right? These numbers are reflecting the numbers from the original glucose molecule. So, this was initially carbon 1, this initially carbon 2, and this initially carbon 3 of glucose. And the G3P that we generated from the last step wound up with carbons 4, 5, and 6 from our initial glucose molecule.

This step that is carried out by triose-phosphate isomerase and has a ΔG that's close to 0, making it readily reversible, converts DHAP into G3P. But notice here that our carbon numbering on the G3P is actually reflecting the carbon numbering from the G3P of the previous step, and this is probably because the person who made these images, or made these diagrams, was getting a little lazy and they just wanted to reuse the molecule. But I want to make sure that I correct this here for you guys because I know that your professor cares a lot about knowing the carbon numbers. So, this is actually carbon number 1, 2, 3 from this DHAP molecule, or rather, carbons 1, 2, 3 coming from the DHAP, but those numbers are actually corresponding to the carbons of the original glucose.

Now, bear in mind that the carbon numbering of the naming scheme here is different than the carbon numbers that I'm adding to these images. The carbon numbers I'm adding into the images, and we'll be continuing to add into the images, are reflecting the carbons from the initial glucose molecule. This is glyceraldehyde 3-phosphate. So, in the context of this molecule, the phosphate is actually bound to carbon 3 of the molecule, but that's actually carbon 1 from our glucose molecule. These numbers that I'm adding in are the numbers from our original glucose molecule.

Alright, moving on to step number 6: it's important to note that from this point forward, everything needs to be mentally doubled. And that's because, with one molecule of glucose, at this point, we'd actually have 2 molecules of G3P. But I'm only going to show what happens to 1 molecule of G3P because there's no point in just copying and pasting the same image, right? So, just bear in mind that all of the subsequent reactions from this point forth are actually happening twice for every one molecule of glucose.

So, step 6, we have Glyceraldehyde-3-Phosphate dehydrogenase, ΔG close to 0. And you can see that in this reaction, we're being shown the numbers from our initial G3P but if we were showing the numbers from the G3P that used to be DHAP, then this would be carbon 1, 2, 3. So you can think of this as 6, 5, or 4 or 1, 2, or 3. Anyhow, this reaction is going to take G3P, and it's going to take NAD+ and an inorganic phosphate, and it's going to add a phosphate group onto that G3P making it 1,3-bisphosphoglycerate. And in the process, it's going to reduce NAD+ to NADH. And we're basically going to say, see you later to that NADH for now. It's going to come back and be important when we talk about cellular respiration, and specifically the electron transport. For now, we can just say 'bye-bye NADH, it's nice knowing you.' There are 2 of you produced for every one glucose. See you later.

Anyhow, looking at our molecules, let's put in those carbon numbers. So we actually are adding a phosphate group on here. So this is, from our again from our original glucose. This is carbon 3, 2, and 1, or 6, 5, and 4, right? So either or.

Now, moving on to step 7, we have Phosphoglycerate kinase. And you see that the ΔG is negative here. This is a favorable reaction. It's actually a little closer to 0 at cellular conditions. In this reaction, we're going to take 1,3-bisphosphoglycerate and ADP and we're going to remove one of those phosphate groups to make 3-phosphoglycerate. And in the process, we're going to create an ATP through substrate-level phosphorylation. So taking a look at our previous molecule, you can see that this would be 1 or 6, 2 or 5, and 3 or 4. And we're actually just going to remove the phosphate group that we had just put on, this should be 3 or 1, this should be 2 or 5, and this, I'm sorry, I mean 4, and this should be 1 or 6. So, we're going to remove the phosphate group that we just added and that's going to leave us with 3-phosphoglycerate and this is again, get our carbon numbers right, that's 3 or 4, this is 2 or 5, and this here is 1 or 6.

Now, step 8, we have 3-Phosphoglycerate mutase. ΔG close to 0, that's why we've got our reversible arrows there. And we're going to take 3-phosphoglycerate and we are going to form 2-phosphoglycerate. So we're basically just going to be moving that phosphate group over by one position. So not a huge change here and again, just put our numbers in. We have 3, 4, 3 or 4, right? It's not 3 and 3 and 4. This is 2 or 5, and this is 1 or 6. And just to be super thorough again, here's 3, 4, 2 or 5, and 1 or 6.

Here’s what students ask on this topic:

What is the significance of carbon numbering in glycolysis?

Carbon numbering in glycolysis is crucial for tracking the fate of each carbon atom from the original glucose molecule through the various steps of the pathway. This helps in understanding the structural changes and the specific positions where reactions occur. For example, when dihydroxyacetone phosphate (DHAP) is converted to glyceraldehyde-3-phosphate (G3P) by triosephosphate isomerase, the carbon numbering helps identify which carbons from glucose are present in G3P. This is important for understanding the metabolic flow and for accurately describing the biochemical transformations that occur during glycolysis.

How does triosephosphate isomerase facilitate the conversion of DHAP to G3P?

Triosephosphate isomerase catalyzes the reversible conversion of dihydroxyacetone phosphate (DHAP) to glyceraldehyde-3-phosphate (G3P). This enzyme has a delta G close to 0, indicating that the reaction is readily reversible under cellular conditions. The conversion involves the rearrangement of the carbon skeleton, where the carbon atoms from DHAP are restructured to form G3P. This step is crucial because it ensures that both molecules derived from the cleavage of fructose-1,6-bisphosphate can continue through glycolysis, ultimately leading to the production of ATP and pyruvate.

What role does glyceraldehyde-3-phosphate dehydrogenase play in glycolysis?

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays a key role in glycolysis by catalyzing the oxidation and phosphorylation of glyceraldehyde-3-phosphate (G3P) to form 1,3-bisphosphoglycerate. This reaction involves the reduction of NAD⁺ to NADH and the addition of an inorganic phosphate to G3P. The reaction is crucial for the subsequent production of ATP through substrate-level phosphorylation. GAPDH's activity is essential for maintaining the flow of carbon through glycolysis and for the generation of reducing equivalents (NADH) that are later used in cellular respiration.

How is ATP generated through substrate-level phosphorylation in glycolysis?

ATP is generated through substrate-level phosphorylation in glycolysis during two key steps. The first step involves phosphoglycerate kinase, which catalyzes the transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate. The second step involves pyruvate kinase, which transfers a phosphate group from phosphoenolpyruvate (PEP) to ADP, forming ATP and pyruvate. These reactions are crucial for the net production of ATP in glycolysis, providing energy for cellular processes.

What is the role of phosphoglycerate mutase in glycolysis?

Phosphoglycerate mutase catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate in glycolysis. This enzyme facilitates the intramolecular shift of the phosphate group from the third carbon to the second carbon. The reaction has a delta G close to 0, indicating that it is readily reversible under cellular conditions. This step is important for preparing the molecule for the subsequent dehydration reaction catalyzed by enolase, which ultimately leads to the formation of phosphoenolpyruvate (PEP), a high-energy intermediate used in ATP synthesis.