Metabolism | Regulation of Pentose Phosphate Pathway

I ninja nerds in this video we're going to continue on with the pentose phosphate pathway and specifically focus on the regulation now if you guys remember I talked about that special enzyme and if you guys remember we had that glucose 6-phosphate if you guys remember we had glucose 6-phosphate and he was being converted into what six phospho glucan o lactone and if you can remember the enzyme that was catalyzing this step was going to be glucose 6-phosphate dehydrogenase right this enzyme was catalyzing this step here and what's important is I told you that this enzyme

is highly regulated in this step and how we determine this is actually based upon again the body's demand so here's the thing people are wondering okay Zach well how do I know that this glucose 6-phosphate will go into the pentose phosphate pathway versus going into glycolysis like what's the stimulus there well glycolysis is dependent upon ATP demands right so glycolysis depends upon the demands of a teepee for example if there's very little ATP you're going to want us to increase whereas the opposite if the ATP is actually too high then what then you don't want

to decrease glycolysis simple as that right same thing goes with the pentose phosphate pathway so it goes like this instead if you guys remember in this step I generate what am I taking I'm taking nad p+ and converting it into nad pH with the whole purpose of this oxidative phase remember there's two phases the oxidative phase and the non oxidative phase and the oxidative phase we're generating a lot of NADPH is and a lot of ribose 5-phosphate right but here's the significant point you're trying to make NADP ages so if you have low in a

d th's right so in other words you know that is low nadph that's when the ratio of in a d ph over in a b p+ who's greater in this case well I have more nadp+ and less NADPH so this ratio is thrown off so now whenever there's low NADPH in this condition so we can describe the ratio concept here is that if there is low NADPH or the ratio of low NADPH for high nadp+ this is a stimulus this is a stimulus to this enzyme that will stimulate it but the opposite can be said

for whenever your NADPH is too high so now what's going to happen with a ratio now I have more NADPH is as compared to my nadp+ so in this situation in this scenario what's happening here now this is low and this is high this situation would apply as an inhibitor okay so let me actually get that stimulation out of it because that's only for this one over here whereas this one is an inhibitor okay so if you already have a lot of NADPH is you're not going to want to keep having this pathway go through

you're going to want to inhibit this enzyme so again let's represent here green green is representing that you have high NADPH whereas orange is stimulatory meaning that you have low NADPH okay and these are the primary regulators of this step now that's kind of general because it's not really a great great explanation of how this actual pentose phosphate pathway is actually occurring this is kind of an oversimplification so what we need to do is we need to go through four different scenarios of how this actual pentose phosphate pathway is really being regular more detail so

there's four scenarios we're going to go through each one of them step by step the first scenario says okay our body is saying that we need to make ribose 5-phosphate and we don't need NADPH which pathways will our body take care of okay okay if you guys remember when we talked about in the previous video that the oxidative phase was generating a lot of NADPH and a lot of ribose 5-phosphate whereas in the non oxidative phase we were gin they are generating a lot of ribose 5-phosphate we didn't use NADPH in that step that's what

we want to do because we don't want NADPH so in this step we want to primarily depend upon the non oxidative phase and think about this for a second when do we need ribose 5-phosphate when we need to make nucleotides all right so whenever we need to make you know things that are going to be specifically for DNA for RNA for ATP for nad for F ad for coenzyme a making those types of things okay so let's explain how this is going to work and we're going to go pretty quick right so again if you

guys remember what can happen in the non oxidative phase let's say I have glycolysis you remember glucose goes to glucose 6-phosphate to fructose 6-phosphate to fructose 1 6 bisphosphate to DHAP which transfer dihydroxyacetone phosphate which can isomerize with GA 3 p but it can also get broken down this gets converted into 1 comma 3 BPG this gets converted into 3 phosphoglycerate 2-phosphoglycerate pep and then eventually pyruvate and then you know because we already talked about in the other video that out of this you're going to generate at least a total of a net of two

ATP from this calculated pathway now in this situation you guys remember that we could take glyceraldehyde 3-phosphate right and what could we do with that we could combine it with fructose 6-phosphate which I'm just showing us f6p if you guys remember these two can react with one another if these two react with one another and the presence of a special enzyme okay and you guys will remember because it's all going to come back to you I'm transferring a two-carbon fragment which enzyme transfers two carbon fragments this is the trans catalase enzyme the trans catalase will

transfer the two carbons from fructose 6-phosphate on to GA 3p he will then turn into xylose five philosophy what can happen with the site goes by phosphate if you guys remember he can be converted into ribose 5-phosphate okay there's one I made one ribose 5-phosphate no NADPH now I can also synthesized from this he transfers the two carbons and he gets converted into a four carbon which is called a ray throws for flossing I'm just denoting it like this now right efore P then if you remember a Ren throws four phosphate and the X Y

P we acted previously because this is a reversible reaction now what happens then we're going to take this a riff throws for philosophy and react with another molecule with that molecule that we had fructose 6-phosphate these two are going to react and they're going to react via a trans aldolase enzyme and they get converted what happens he takes his to three carbons transfers it on to him he gets converted to said yellow half toast seven phosphate and he gets converted into glyceraldehyde 3-phosphate then what happens then that schedule o hep toasts seven phosphate combines with

the glyceraldehyde 3-phosphate in the presence of a trans Quiles and that transfers a two carbon schedule ejeta seven phosphate transfers two carbons from him onto the GA 3p he gets two carbons he's going to turn into silos five phosphate and he'll turn into rival those five philosophy oh now what did I just do i synthesized ribose 5-phosphate from this way and you guys know eventually we'll just show it here and it green that the xylose five phosphate can eventually get converted into ribose 5-phosphate how many ribose 5-phosphate did i generate from this glycolysis pathway i

generated three ribose 5-phosphate from the glycol and can read it so from glycolytic intermediates okay that's how we would deal with this scenario so when our body needs to make our 5p what do you do you have the glycolytic intermediates feed into forming how many ribose 5-phosphate one two and then eventually this one can get converted into the third one so we'll just circle this x5p which will eventually get converted into our FIP so we made three of them okay let's go to scenario two the second scenario says okay we need ribose 5-phosphate and we

need NADPH okay so now this one should be easy to remember and the reason why this should be easy to remember is because I remember from the oxidative phase Zack was saying that we make NADPH and ribose 5-phosphate huh well look at that I'm going to do the oxidative phase so I'm going to do the oxidative phase because I remember Zack saying all when I did the oxidative phase I make ribose 5-phosphate and NADPH and let's think about this when we need to do this ribose 5-phosphate is needed for making again fa d nad ATP

RNA DNA a lot of different things Co a what does NADPH needed for nucleotide synthesis neurotransmitter synthesis it's needed also for fatty acid synthesis cholesterol synthesis this cell could be getting to replicate divide we need this whenever maybe the cells replicating okay let's go through this process then so let's say here we now take and show you what's going to happen here well then what happened with that glucose oh we have glucose here he gets converted into glucose 6-phosphate but the body says oh you know what I'm going to take this and I'm going to

shunt it into the oxidative phase what happens in the oxidative phase in the oxidative phase I utilize a special enzyme and that enzyme is called glucose 6-phosphate dehydrogenase which does what it converts glucose 6-phosphate into I'm going to abbreviate it six phospho glucan o lactone then what happens that six phosphate leucon a lactone gets converted into six phospho gluconate okay so this is going to get converted into six phospho gluconate then what happens the six phosphate gluconate gets converted into ribulose 5-phosphate and then what happens with that ribulose 5-phosphate you know that the ribulose 5-phosphate

I'm going to put ribulose for this one but you know that the ribulose 5-phosphate gets converted eventually into ribose 5-phosphate through the isolation enzyme right and this will get converted into ribose I'm going to put our 5p ribose 5-phosphate okay so this is the importance here and so again if you remember what enzyme is here not as important of a one what it's called lactamase what enzymes here it's six phospho gluconate dehydrogenase now that's not the important points of all this what's the important point of all this I generate an NADPH in this step and

I generate a in a DP H in this step okay so what I just doing this step guys i generated my NADPH is that my body needed and I generated my are five P's that my body needed okay and why is this good again because this cell could be dividing so it needs ourselves to be making certain types of DNA RNA specific types of nucleotides and and different types of cholesterol fatty acids and so on and so forth okay okay now it's going to the scenario number three so what if scenario number three safe scenario

number three says okay we don't need ribose 5-phosphate so there's no need for the ribose 5-phosphate but we do need NADPH so if I need to do NADPH huh this is a really tricky one this one's a weird one so we're not going to write down exactly what's happening actually I will write down what's happening but we're going to have to explain it in a different way so now two phases are occurring the oxidative phase and gluconeogenesis okay so two phases are occurring they're two things oxidative phase and gluconeogenesis let's explain how this is happening

this one's a little bit weird but let's see if we can stick in there okay so if you guys remember what's the oxidative phase similar to this let's just blaze right through that okay so let's just blast right through that really really quickly just one of the red glucose to glucose-6-phosphate right then that glucose 6-phosphate can do what it can then get converted into six phospho glucan o lactone which can get converted into six phospho gluconate which can get converted into a method our i5p which stimulates the simulates that that's ribulose 5-phosphate and then that

gets converted into ribose 5-phosphate now in a different color here I'm going to remember that your g6p he eventually gets converted into fructose 6-phosphate and then it's a fructose 1 6 bisphosphate then 2 DHAP then into GA 3p which is your glyceraldehyde 3-phosphate and then eventually the pyruvate right ok in this step which ones specifically this step here when I go from glucose 6-phosphate to six possible Guk on a lactone I take nadp+ and I convert it into NADPH okay cool and then from six Vosloo econo lactones of rib you Lowe's 5 phosphate I take

nad p+ and I convert it into and the ph cool and if you remember just to reiterate this is glucose 6-phosphate dehydrogenase this is lactase and this is specifically six phosphoglucomutase now I made our 5p well I just said I don't want to make our 5p what do I do with that watch this you guys remember all those steps that we covered then eventually we're not going to go through every single one of them but you guys realize that all that non oxidative phase is reversible so eventually what can I do with that our 5p

let's do this in a nice pink color I can eventually take that ribose 5-phosphate and I can convert it into glycerol 3-phosphate eventually right and in the same way I can take that ribose 5-phosphate and also convert it into what fructose 6-phosphate now what can happen this step is reversible so I can take glycerol 3-phosphate into fructose 1 6 bisphosphate then if I want to go from fructose 1 6 bisphosphate to fructose 6-phosphate it is regulated by the fructose 1 6 bisphosphate eizan's on but I can go backwards and I can go backwards here and

depending upon if we are in the liver and the kidneys or the small intestine there is a special enzyme here that can convert the glucose 6-phosphate into glucose and that's called the glucose-6-phosphatase but eventually what happens this R 5 P can make GA 3 P and fructose 6-phosphate which can eventually be turned converted into glucose and what happens is I use up all my ribose by phosphate so I don't have any of them so what's the whole purpose here all I really did is generate a lot of NADPH and used up my ribose 5-phosphate to

make glucose so it's an intelligent design our body has and this can occur based upon our needs maybe we need to have a lot of biosynthesis reactions because we need to make NADPH for synthesizing fats or synthesizing cholesterol or synthesizing their Oh transmitters are synthesizing nucleotides you get the point or our body needs glucose because I don't need anymore our 5p okay now last scenario number 4 let's say that our body needs NADPH and it needs ATP it's going to be very very similar to this one let's do this one in green so now same

thing glucose to glucose 6-phosphate to fructose 6-phosphate to fructose 1 6 bisphosphate to DHAP glyceraldehyde-3-phosphate and again these are isomerized and then eventually you realize that this can go to pyruvate and you know that out of this I generate what a net of 2 ATP ok same thing like we've talked about glucose 6-phosphate can get converted into what let's actually do this in a different color since we've used this one already let's do this one in blue so glucose 6-phosphate can be acted on by glucose-6-phosphate dehydrogenase which will do what take nadp+ and convert it

into an ADP H ok cool and I make 6 phospho bukata lactone then I can take that 6 philosopher books on a lactone convert into 6 phosphor gluconate and then I can convert that into red Bulow's 5 phosphate and then I can convert that into ribose 5-phosphate just like I did in the previous one over here but now watch this and then again what is this enzyme your cold this one is called 6 phospho gluconate dehydrogenase why is that important because I generate a NADPH from here so let's kind of you know bubble these guys

up here because I made my NADPH so I took care of that part of my body's demands now what's the problem ok now what I'm going to do is I'm going to take this ribose 5-phosphate and depending upon the body's need instead of them making glucose I can take that ribose 5-phosphate convert it into glyceraldehyde-3-phosphate what else can I do I can recur it into I can convert it into fructose 6-phosphate where can these guys go they can go down they can go from fructose 6-phosphate into fructose 1 6 bisphosphate that can go down into

DHAP air 2 glyceraldehyde 3-phosphate and that eventually could go down into pyruvate and what will that do that will help to generate ATP and then we take care of the body's demands because it needed ATP so this is the way that the body can do this ok now we know all of these scenarios ok and then what would be this what would be the situation for this we would want to do the oxidative phase here and what else would we want to do glycolysis ok last thing I want to talk about guys why is all

this important because just knowing all these things ok that's cool it's cool thing to know but why is this significant why is this important ok it is important again because if you guys remember just real quickly NADPH is important for what things he's important for a lot of different pathways ok what is it lipid synthesis cholesterol synthesis neurotransmitter synthesis and even nucleotide synthesis right so a lot of different things he's used for ok what is significant about the RF IP one more time ok so now for our 5p ribose 5-phosphate he's significant because if you

remember he can do a boatload of stuff right he can help with DNA synthesis RNA synthesis ATP synthesis NAD+ and FA D synthesis and also coenzyme a synthesis so he's involved in all these reactions so you can see how going through all of these scenarios you can basically determine what just what the body will do which one of these actual pathways will occur based upon the body's demands for these two molecules or for ATP needs also as we saw in scenario 4 ok last thing here our bodies very very interesting we have a way of

controlling something what did I told you it was one of the really cool ones I told you that we were going to mention free radical reactions why is this important because free radicals are extremely dangerous let's go through a quick free radical pathway extremely quick oxygen you know whenever you can actually have it at the electron transport chain certain times he can actually be converted into it's called a superoxide anion which just means you've got an electron plucked out and I use a radical now when this happens two things can happen one thing is I

can convert this into a very deadly chemical called peroxy nitrite but this will only happen if I have the presence of a nitric oxide radical so you know nitric oxide radical can also be formed within our body so here's our nitric oxide radical this nitric oxide I trick oxide radical can combine with this molecule so what is this called this is called super oxide anion which is a radical this is our nitric oxide radical when these combine they can make peroxy nitrate why it production nitrite why is that dangerous because this can cause very very

dangerous effect it can oxidize proteins which can correct them up destroy them it can nitrate proteins which can alter their activity it can inactivate enzymes maybe that control like channels within the body and the dangerous dangerous part it can cause lipid peroxidation which can cause very very dangerous effects also to our cell membranes okay but our body is very interesting it has a way to deal with this superoxide anion what it can do is it has an enzyme here this enzyme is called superoxide dismutase so it's called superoxide dismutase what's superoxide dismutase also consists of

manganese within it's important it takes the superoxide anion and converts it to a less dangerous molecule less less dangerous molecule still dangerous but not as dangerous this is called hydrogen peroxide so again what is this molecule called hydrogen peroxide now there's three destinations of this guy okay one is this hydrogen peroxide becames actually if you convert into another dangerous molecule this extremely probably one of the worst ones is called a hydroxyl radical this is called a hydroxyl radical the hydroxyl radical can cause DNA damage so those free radicals that you generate from the actual hydroxide

free radical can damage DNA it can damage the lipids can cause lipid peroxidation and it can also damage our proteins and enzymes and this can lead to a lot of cytotoxic effects killing the cell now this can happen we can actually control this via the Fenton reactions so Fenton reactions can occur on certain steps over here now we'll just put that so Fenton or you can put some iron in there Fenton reactions anyway we're not going to talk too much about that here's the important part the hydrogen peroxide can have another thing you know there's

enzymes called catalase as we talked about this in the peroxisomes the catalase is can convert the hydrogen peroxide into you know water and oxygen but here's why and then technically it's one-half of an oxygen if we were to be really really particular but here's where it's important this step here taking this hydrogen peroxide and converting it into another molecule a guy can also can convert it let me actually do this in a different way I'll do it like this I can convert it into water and oxygen also but another special enzyme this enzyme is called

glutathione peroxidase and this enzyme is actually helping to convert hydrogen peroxide into water and oxygen now here's the problem here's what can happen we need to talk about another enzyme it's extremely extremely important last enzyme because the default in this enzyme can cause disastrous effects on the body so let's do it over here okay let's get this out of the way alright so now there is a molecule in our body called glutathione now glutathione I'm just going to draw it as a I'm going to put a G so I'm going to represent this you're going

to see it from now on as a G you're just going to see it as a G glutathione is special because if I have a glutathione technically in its reduced form it has this style group so this is its reduced form glutathione is our natural antioxidant in the body but you know what happens you know those hydrogen peroxides and superoxide and so you remember the hydrogen peroxide that you had here this glutathione can react with this hydrogen peroxide and when it does it actually can convert this hydrogen peroxide into water and that oxygen you can

also do this with other different molecules but there's another enzyme involved in this stuff this enzyme is called glutathione okay this is called the peroxidase enzyme right so we talked about that one over there but when this glutathione in the reduced form unloads its high drives with high drives again it's basically a proton and two electrons and now unloads it onto this hydrogen peroxide and helps to convert it into water and half of an oxygen what happens to him in that same process is look what happens he gets converted from the reduced form into a

different form look what happens damn I take a glutathione molecule and another glutathione molecule and now I'm going to link them together okay through this disulfide bond so look what happened here glutathione I might have two of these let's say that I have two individual one of these and what are they doing they're taking and dropping off hydride ions onto this hydrogen peroxide or other free radicals to convert them into less toxic forms but and the process they get converted into the oxidized form why is that bad because then they can't drop any high drives

onto the actual what they can drop any hydride ions onto this hydrogen peroxide so now it's not going to be able to get rid of these free radicals this is where these NADPH has come in so now what I'm going to do is I'm going to do something cool let me actually show cuz I'm going to let show it here I'm going to convert this guy back to this guy but let me show you exactly how that's happening right up above this look at this I'm going to have glutathione with a Thyle glutathione with a

thio group okay that's how we're going to represent it then it's going to react with the hydrogen peroxide to convert it into what h2o and half of an oxygen but then what happens this gets converted into the oxidized form of glutathione in order for me to go back to this I need those in ad ph's they're going to do what they're going to drop those hydrides off onto the glutathione in the oxidized form now what's going to happen it's going to go back to the reduced form that's amazing that's the way our body deals with

these free radicals those NADP ages that we're making from the oxidative phase that we're making from the pentose phosphate pathway right we're going to use that to drop on to these oxidized glue the scions to convert them back into the reduced form and the enzyme involved in this step is called glutathione reductase call glutathione reductase which should make sense because it's reducing the glutathione now why is this bad if you guys remember an anemia as we talked about this whenever there is a deficiency in that enzyme where's that enzyme at let's find him this guy

when there's an efficiency in this enzyme you're not making this enzyme glucose 6-phosphate glucose 6-phosphate dehydrogenase due to some type of mutation and which this enzyme is lost can you make any dphh no if you can't make any DPH NADPH is can you unload those onto the glutathione is involved in the free radical reactions no what happens you lead to the formation of Heinz bodies remember Heinz bodies we talked about it in anemias you guys watch that video it's basically you're going to have those reactive oxygen species so remember you have all those reactive oxygen

species like the end of the superoxide anion the hydroxyl radical the peroxy nitrite so I'll put peroxy nitrite tons of different you know even what hydrogen peroxide even accumulating it's basically damaging what molecule inside of our red blood cells hemoglobin and what was it doing to the hemoglobin it was causing that hemoglobin to stick to the wall remember we had a red blood cell here let's say here's my red blood cell remember it was actually causing the actual hemoglobin to get stuck with the inner wall of the actual red blood cell membrane making it less

pliable less flexible what did that result in the overall result was it lacked led to chemo lytic anemia and then hemolytic anemia is very very dangerous right because it can cause a lot of problems low oxygen carrying capacity it could actually cause the hemoglobin to be released into the bloodstream and can actually also cause the iron to get released into the blood which is also very toxic so there is certain conditions in which people actually follow beans there's some chemical in the fava beans that actually reduce the g6pd H and other different types of things

but the whole purpose is is that the Enzo's phosphate pathway is a beautiful pathway and our body really does depend upon it in order for us to be able to do a lot of different activities iron engineers I hope you guys enjoyed this video I hope you guys really really hope that made sense if it did guys please hit that like button please subscribe we really depend upon you guys subscribing because we look forward to doing this also comment we look forward to hearing from you guys iron is nerds until next time