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Pentose phosphate pathway

Video transcript

when talking about carbohydrate metabolism we can't forget to mention the pentose phosphate pathway 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 just symbolizing 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 a TP 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 is it fit into 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 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 5-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 is deoxyribose and in RNA it's just ribose but in either case this ribose 5-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 and of course for the phosphate in this molecule H NADPH so this is not to be confused with the NADH which if you recall 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 an a G H 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 it's interconverted with NADH and and ad p+ is interconverted with an 8 D pH so of course the H forms of these molecules are the reduced form of these molecules and the + or oxidized form of these molecules are the NAD+ and NADH 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+ to NADH is about a thousand in other words if you took the amount of nad + 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 nad + nadp+ divided by the amount of NADPH you would get point 1 so essentially what this is telling us is that there's a lot of nad + in the body and a lot of NADPH in the body but not much of nadh or nadp+ 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 + 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 I'm going to go ahead and write that here so the biggest role of NADPH in the 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 reactions 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 all right 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 where 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 n/a D pH so that is the big product of the oxidative phase so we actually start out with glucose 6-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 6-phosphate into the oxidative phase of the pentose phosphate pathway and glucose 6-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 rip you loose five phosphate and it's really not important to know except for the fact that it kind of sounds like ribose 5-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 5-phosphate so let's see how that happens let's go ahead and scroll down here so rip ulis five phosphate is actually broken down by eight enzyme a I summary 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 5-phosphate so that's key so remember that's one of our main products of the pentose phosphate pathway now another key point of the non oxidative phase so we produce of course ribose 5-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 6 phosphate and glyceraldehyde-3-phosphate and fructose 6-phosphate that you might be familiar with that come from glycolysis and remember that these are not all 5 carbon sugars right you know glyceraldehyde 3-phosphate is actually a 3 carbon sugar so the ability to interconvert sugars through enzymes like the trans aldolase and the trans peel ace will essentially allow cell to produce more ribose 5-phosphate for DNA and RNA synthesis if needed and now I do want to say this with one caveat which is although these glycolytic intermediates can be re inter converted into ribose 5-phosphate they cannot go all the way up the pathway to glucose 6-phosphate so these oxidative phase reactions are irreversible so shown by kind of the unidirectional arrow arrow but the non oxidative phase of course allows inter conversion 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 side 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 is no ATP consumed or produced in this cycle so that's what makes the pentose phosphate pathway unique