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Pentose phosphate pathway

Video transcript
- [Voiceover] When talking about carbohydrate metabolism we can't forget to mention the pentose phosphate pathways. So, where does the pentose phosphate pathway fit into the breakdown of glucose? So, let's go ahead and review the breakdown of glucose as we normally kind of usually conceive of it as. So, we go ahead and start out with glucose, which I'm drawing here to symbolize it with a six-carbon sugar backbone. And we usually imagine that glucose begins to be broken down in the cytosol of the cell through a series of reactions that we call glycolysis. And then, of course, it goes through the Krebs cycle in the mitochondria, also known as the TCA cycle. And then, finally, it goes to the electron transport chain in the mitochondria to produce ATP. So, that's kind of usually the end product we think of when we think about breaking down glucose. But, the pentose phosphate pathway is kind of a unique pathway, because it turns out that in this pathway no ATP is consumed or produced. That's kind of unique, to point out. So, where does it fit in to this overall pathway? It turns out that the linear way I've written cellular respiration is actually only partly true. It's a great way to conceptualize it, but there are many branches or kind of side reactions that are taking place almost simultaneously with the breakdown of glucose, and the pentose phosphate pathway is one of these. So, turns out that as glucose begins to go through glycolysis, some of it is shunted away to become the pentose phosphate pathway. So, glucose continues to be broken down, but it continues to be broken down to produce different products than it would if it continued through going through glycolysis, and Krebs, and then to the electron transport chain. So, as you can see, I've written pentose phosphate pathway kind of suggestively by highlighting pentose and phosphate in different colors to point out to you that there are two primary products in this pathway. So, the first is the production of a five-carbon pentose sugar. So, pentose is just another word for five-carbon sugar, and the particular name of this sugar is ribose-five-phosphate. And this sugar, so it's a five-carbon sugar, I'll go ahead and draw that to remind us of that, is an important substrate in producing DNA and RNA. So, if you remember, DNA and RNA contain nucleotides, and the nucleotides contain a nitrogenous base, a phosphate group, and a five-carbon sugar. So, in the case of DNA, it's deoxyribose, and in RNA, it's just ribose. But, in either case, this ribose-five-phosphate is an important precursor to creating DNA and RNA, so, quite a crucial molecule. Now, the second primary product of this reaction, as this phosphate nicely implies, is a phosphorylated molecule that is usually abbreviated as N-A-D-P, P standing of course for the phosphate in this molecule, H. NADPH. So, this is not to be confused with the NADH, which, if you recall, I'll go ahead and actually draw that in here, if you recall, NADH is actually produced in cellular respiration during the breakdown of glucose. So, this produces NADH, which, of course, contributes electrons to the electron transport chain. So, of course, the question you might have in your mind is how is NADH different from the easily confused NADPH, because they sound like similar molecules, and in many ways they are. So, they actually both exist in pairs inside the cell, so, NAD-plus we know is inter-converted with NADH, and NADP-plus is inter-converted with NADPH. So, of course, the H forms of these molecules are the reduced form of these molecules, and the plus, or oxidized form of these molecules, are the NAD-plus and NADP-plus. But, what's different about these two pairs of molecules is the relative amount of the reduced form and the oxidized form inside the cell. So, just to give you a sense of that, the ratio of NAD-plus to NADH is about 1000. In other words, if you took the amount of NAD-plus and divided it by the amount of NADH in the body, you would have about 1000 times more NAD-plus. On the other hand, if you took the amount of NADP-plus divided by the amount of NADPH, you would get 0.1. So, essentially what this is telling us is that there is a lot of NAD-plus in the body and a lot of NADPH in the body, but not much of NADH or NADP-plus. And, knowing this actually helps me remember and differentiate between the role of NADH and NADPH inside the body. So, first, I reason out to myself that if there's a lot of NAD-plus present in the body, most of the NAD-plus will want to accept electrons. And, of course, the biggest role in accepting electrons comes in the breakdown of glucose and producing NADH, so that makes sense. On the other hand, the primary role of NADPH, which is what we have the majority of, is to donate electrons, so I'm gonna go ahead and write that here. So, the biggest role of NADPH in the body is to donate electrons, and that, of course, would not be very helpful in breaking down glucose, right? Because, the breakdown of glucose donates electrons, it doesn't accept them. Now, I will remind you that donating electrons is really important in anabolic reaction. So, remember that anabolic reactions involve building up molecules, such as in the synthesis of fatty acids, for example. And so, NADPH plays a vital role in kind of providing this reducing power, so to say, for these anabolic reactions. In addition, I'll briefly mention that NADPH also uses its reducing power, its ability to donate electrons, to maintain the store of antioxidants inside the body. So, you know, kind of an ironic part about having oxygen as a requirement for cellular respiration is that some of this oxygen can become really reactive if it gains an extra electron. And so, the goal of kind of some of the molecules in your body are to serve as antioxidants to kind of trap these reactive oxygen species from reacting with important things in your body, like DNA or proteins. And so, once they do that, of course, some of these antioxidant molecules, in the process of reacting with a reactive electron-rich oxygen molecule become oxidized. And so, of course, NADPH can come in and save the day by donating electrons to reduce the oxidized form of these antioxidants back into their reduced form so that they can again react with any rogue reactive oxygen species. Alright, so now we're ready to look at the pentose phosphate pathway in more detail. So, I'm going to go ahead and bring up a diagram of how the pentose phosphate pathway is usually represented in most textbooks, and this is a lot of detail, admittedly. And, I don't want you to get lost in the details, so I'm going to try and break it down and hone your attention to the most important details to take away from this. So, the first of these important details is to note that there are two big phases of the pentose phosphate pathway. So, the first is called the oxidative phase and the second is called the non-oxidative phase. And, you know, as the name implies, oxidative phase we're oxidizing. So, remember that breakdown of glucose, breakdown of carbohydrates, is an oxidative process in general. And, in this phase, the big idea here is that we are producing NADPH, so that is the big product of the oxidative phase. So, we actually start out with glucose-six-phosphate here. So, just note that we start off with this molecule here, which I'll remind you is one of the first metabolites that's produced in glycolysis. So, this is essentially shunted from glycolysis, which, of course, starts out with glucose. So, glucose enters glycolysis and some of it will continue through cellular respiration, but the other part of the glucose will then be shunted through this glucose-six-phosphate into the oxidative phase of the pentose phosphate pathway. And, glucose-six-phosphate is then broken down in a series of steps which aren't entirely important, but the key idea here is that you're producing NADPH along the way. Now, the non-oxidative phase starts with this molecule called ribulose-five-phosphate, and it's really not important to know except the fact that it kind of sounds like ribose-five-phosphate, right, which I mentioned before was one of the main primary products of the pentose phosphate pathway and indeed, it's a precursor for the ribose-five-phosphate. So, let's see how that happens. Let's go ahead and scroll down here. So, ribulose-five-phosphate is actually broken down by an enzyme, an isomerase. So, it's essentially switching around the molecule. It's not really changing the chemical formula, but it's switching around the structure to ribose-five-phosphate. So, that's key. So,remember that's one of our main products of the pentose phosphate pathway. So, another key point of the non-oxidative phase, so we produce, of course, ribose-five-phosphate. Another key point here is that we're also able to interconvert various sugars, so interconvert sugars. And why is this important? This turns out to be really handy for the cell, because notice here that there are some products, like fructose-six-phosphate and glyceraldehyde-three-phosphate and fructose-six-phosphate that you might be familiar with that come from glycolysis. And, remember that these are not all five-carbon sugars, right, you know that glyceraldehyde-three-phosphate is actually a three-carbon sugar. So, the ability to interconvert sugars through enzymes like the transaldolase and the transketolase will essentially allow cells to produce more ribose-five-phosphate for DNA and RNA synthesis if needed. And, we do want to say this with one caveat which is although the glycolytic intermediates can be reinter-converted into ribose-five-phosphate, they cannot go all the way up the pathway to glucose-six-phosphate. So, these oxidative phase reactions are irreversible. So, shown by kind of the unidirectional arrow, but the non-oxidative phase, of course, allows interconversion and hence is kind of thought of as more of a reversible pathway. So, that, in a nutshell, is the pentose phosphate pathway, and I'll return to the kind of main slide at the beginning and just remind you that the key takeaway is that we are producing a pentose sugar, ribose, and a phosphorylated molecule, NADPH, in this pathway, and that the most unique part of this pathway is that even though we classify it as part of carbohydrate metabolism because it utilizes the metabolites from the breakdown of glucose, there's no ATP consumed or produced in this cycle, so that's what makes the pentose phosphate pathway unique.