Pyruvate Oxidation - Online Tutor, Practice Problems & Exam Prep

Cellular respiration continues with the citric acid cycle, following glycolysis. Pyruvate, produced in glycolysis, is transported to the mitochondrial matrix where it undergoes oxidation by the pyruvate dehydrogenase complex. This reaction generates acetyl CoA, CO₂, and reduces NAD⁺ to NADH. Acetyl CoA, derived from pyruvate, plays a crucial role in subsequent metabolic pathways. Understanding the substrates, products, and regulation of this process is essential for grasping the overall energy production in cells.

Pyruvate Oxidation

In these videos, we're basically going to be picking up our story where we left off last time. You might recall that we ended with glycolysis last time. That's sort of where we ended our story of cellular respiration and you can kind of think of glycolysis as act 1 of cellular respiration. In these videos, we're going to be covering act 2 which is the citric acid cycle. And in fact, next time, we will finish with the 3rd and final act which is going to be electron transport and oxidative phosphorylation. So the point is if you're not totally comfortable with what was going on in glycolysis, you might want to go and review that before jumping into these videos because we're just going to be continuing the story and we're not really going to be reviewing that material. The assumption is you already understand it by the time you're here. So let's begin with pyruvate oxidation. Now, a little recap. You might recall that glycolysis ends with, glucose being turned into 2 molecules of pyruvate and then all of this is taking place in the cytosol. Now, our pyruvate is going to be transported from the cytosol into the mitochondrial matrix. And what's, what's important that I want you to, you know, make sure you're aware of, is that we are only going to be looking at the path of 1 pyruvate. Right? Remember that there's 2 coming off of glucose. So, if you are trying to, you know, do your sort of like mental accounting of all the substrates and products and all that, be aware that, you know, if you're coming from glucose, you need to double the numbers that you're seeing now. And when we finish up our discussion of the citric acid cycle, we will be going through a grand accounting of all the substrates and products and all that sort of stuff that we have talked about. And I'll be very explicit about the numbers relating to one glucose, etc. So just for now, be aware, we're only looking at the path of 1 pyruvate, not the 2 that are going to come off of glucose. Okay. Without further ado, pyruvate dehydrogenase. Dehydrogenase. This is going to pick up pyruvate once it enters the mitochondrial matrix. And you can see from its delta G, this is a favorable reaction. And it's actually a complex of 3 enzymes, but you don't really need to worry about their names. I've included them for the sake of thoroughness but don't worry about memorizing it. It's not very important. What you do need to know are rather the substrates, products, cofactors, and how this enzyme is regulated. So let's start with the substrates. Again, we are our reaction with pyruvate. That one's kind of obvious. You should know the structure of this molecule already. Be very familiar with it and, we also use the substrate NAD⁺ and coenzyme A. And just take note, this is the reduced form of coenzyme A. That's what that SH is symbolizing. And, we are going to generate from this reaction. Our products are going to be CO₂. This is going to come off as CO₂. We're going to talk more about that, momentarily. Our NAD⁺ is going to be reduced to NADH and talk about more a little more about that in a second too. And lastly, our product is going to be acetyl CoA or our main product, right? What pyruvate is going to become and what's going to carry on in the, subsequent reactions is Acetyl CoA, this molecule you see here. So, the cofactors, you need to know what they are but the only note I really want to make about them is FAD because it's kind of interesting what happens here. You see, FAD is going to be in the course of the reactions. FAD, write this over here. FAD is going to be reduced to FADH₂. Now the reason I've drawn my arrow kind of weird and backwards, to demonstrate this is because this is actually going to, FADH₂ is actually going to reduce NAD⁺ and turn back into FAD, right? This is a cofactor so it's going to be, you know, we're going to be reusing this FAD, in subsequent reactions. So FAD gets reduced to FADH₂. That's going to reduce our substrate NAD⁺ into NADH. We're going to regenerate FAD and pick up another pyruvate, do another reaction, so on and so forth. Interesting little note there. And lastly, just want to again make the point that glycolysis glycolysis was taking place that was a weird s. Glycolysis was taking place in the cytoplasm. I'm sorry. Let's call it the cytosol. And the, reactions are now pyruvate, right, has moved into the mitochondrial matrix. So that is where all of these reactions that we're going to be talking about now are taking place. Last note I want to talk about, everyone's favorite subject I know, counting carbons. And you might recall a little review here that from glycolysis, we are left with 2 Pyruvate and they will have the numbering scheme of 1

Here’s what students ask on this topic:

What is the role of pyruvate dehydrogenase in cellular respiration?

Pyruvate dehydrogenase is a crucial enzyme complex in cellular respiration that catalyzes the conversion of pyruvate into acetyl CoA. This reaction occurs in the mitochondrial matrix and is essential for linking glycolysis to the citric acid cycle. The process involves the decarboxylation of pyruvate, releasing CO₂, and the reduction of NAD⁺ to NADH. The acetyl CoA produced then enters the citric acid cycle, where it undergoes further oxidation to produce ATP, NADH, and FADH₂, which are vital for energy production in cells.

How is pyruvate transported into the mitochondrial matrix?

Pyruvate is transported from the cytosol into the mitochondrial matrix via a specific transport protein known as the pyruvate translocase. This protein functions as a symporter, coupling the transport of pyruvate with a proton (H⁺) across the inner mitochondrial membrane. This transport is essential for the subsequent oxidation of pyruvate by the pyruvate dehydrogenase complex, which takes place in the mitochondrial matrix.

What are the substrates and products of the pyruvate dehydrogenase reaction?

The substrates of the pyruvate dehydrogenase reaction are pyruvate, NAD⁺, and coenzyme A (CoA-SH). The products of this reaction are acetyl CoA, CO₂, and NADH. The reaction can be summarized as follows:

${\mathrm{pyruvate}}_{}+{\mathrm{NAD}+}_{}+{\mathrm{CoA}-\mathrm{SH}}_{}\to {\mathrm{acetyl}-\mathrm{CoA}}_{}+{\mathrm{CO}2}_{}+{\mathrm{NADH}}_{}$

Why is the conversion of pyruvate to acetyl CoA considered a key regulatory step in cellular respiration?

The conversion of pyruvate to acetyl CoA by the pyruvate dehydrogenase complex is a key regulatory step in cellular respiration because it links glycolysis to the citric acid cycle. This step is tightly regulated by various mechanisms, including allosteric inhibition by its products (NADH and acetyl CoA) and covalent modification (phosphorylation). This regulation ensures that the cell efficiently manages its energy resources and responds to changes in metabolic demands. By controlling the flow of carbon into the citric acid cycle, the cell can balance energy production with the availability of substrates and the need for biosynthetic precursors.

What cofactors are involved in the pyruvate dehydrogenase complex, and what are their roles?

The pyruvate dehydrogenase complex requires several cofactors for its activity: thiamine pyrophosphate (TPP), lipoic acid, FAD, NAD⁺, and CoA-SH. TPP assists in the decarboxylation of pyruvate. Lipoic acid acts as a swinging arm, transferring the acetyl group. FAD is reduced to FADH₂ and then reoxidized, facilitating the reduction of NAD⁺ to NADH. CoA-SH accepts the acetyl group to form acetyl CoA. These cofactors ensure the efficient conversion of pyruvate to acetyl CoA, enabling the continuation of cellular respiration.