Pentose Phosphate Pathway - Regulation, Purpose and Importance in Human Health

hey everyone in this I'm going to talk to you guys about the pentos phosphate pathway or otherwise known as the pentos phosphate shunt I'm going to talk to you guys about how this pathway operates why the pathway is so important to human health I'm also going to tell you guys about some of the regulation of the pathway which tissues tend to use as pathway the most and finally I'm going to talk to you guys about some problems that can occur if this pathway doesn't operate um correctly um and I'm going to show you some examples

or tell you some examples of some human health conditions that can occur if this pathway doesn't operate correctly so um to begin what is the pentos Fate pathway well the pathway is also known as the hexos monophosphate chunt um it occurs in virtually all cell types and tissues um one of the main utilizers of the pathway is the liver which utilizes 30% of his glucose um for the pendos Fate pathway other tissues um that utilize this uh pathway quite a bit are the red blood cells um to maintain ox oxidative capacity the liver also utilizes

this Pathway to um uh to uh protect itself against oxidative stress due to drug metabolism um and some of the tissues that don't utilize this pathway so much include uh muscles muscles uh don't utilize this pathway so much um this pathway occurs in the cytoplasm um it produces nadph now um nadph is very necessary for several Pathways one includes um fatty acid synthesis um 50% of nadp typically goes to fatty acid synthesis um again as I mentioned before nadph um is necessary for oxidative stress homeostasis so this is why we see the liver and red

blood cells using the pathway um they do so to generate nadph to protect themselves against oxidative stress and uh nadph is also important for cytochrome p450 enzymes and this is again important in the liver um this uh pentos phosphate path also produces trioses hexoses and pentoses and pentoses are necessary for nucleotide synthesis so where does this all begin well the pathway actually begins uh near the beginning of glycolysis pathway with glucose 6 phosphate so what happens is instead of um glucose 6 phosphate going down um the glycolysis pathway it gets shunted into another pathway um

by the enzyme glucose phosphate dehydrogenase so glucose glucose 6 phosphate dehydrogenase converts glucose 6 phosphate to glucono one5 lactone 6 phosphate and in doing so it actually takes an nadp+ and reduces it to an nadph now this uh step of the pendos pathway is actually the rate limiting step and um nadph the product of the step actually inhibits the enzyme low levels of nadph can actually activate this enzyme as well so once you have glucono one5 lactone six phosphate Um this can actually be converted into six foso gluconate which then can be converted into ribulose

5 phosphate and this is done by the enzyme six phos gluconate dehydrogenase um and again in this step nadp plus is uh actually uh reduced to nadph so this is again another important um step of the pathway so for this pathway guys I want you to remember that um the the first and the third step of the pathway are the ones that generate nadph and and I want you guys to try to remember these two enzymes now once you have rulos 5 phosphate it can do a couple different things um one it can actually get

converted to xylos 5 phosphate by rulos phosphate 3 epimerase and then the xylos 5 phosphate can actually be redirected um back into the glycolysis pathway um by getting converted into fructose 6 phosphate by transketolase so once uh once the cell kind of generates its nadph it can actually redirect its its end product back into the glycolysis pathway so that uh the cell can actually generate ATP from from that substrate so uh this is it's it's incredibly clever how the cell can actually do this if it needs ADP it can just redirect it into the pendos

phosphate pathway and then back into the glycolysis Pathway to get some ATP from as well um another way or another thing that the rulos 5 phosphate can do is it can actually be converted into um ribos 5 phosphate by ribos phosphate isomerase enzyme once you generate ribos 5 phosphate it can actually be converted into five phosphor robil one pyrophosphate or prpp now this is the this is the molecule I want you guys to remember this molecule is very very important um in medicine and we always want to know this because this molecule we can direct

can be directed into peridine or purine synthesis so this is the molecule that really determines primi and purine synthesis um for cells so prpp remember that guys five phosphor robil one pyros so now that you guys know um the importance of prpp um for peridine and purine synthesis now um what can happen is in in cells that have nucleotides um this the nucleotides can actually be broken down into ribosy phosphate now ribosy phosphate can be converted into um back into some of these earlier steps so I it I I show these arrows as one directional

but a lot of these are reversible so what can happen is ribos f phosphate can actually be redirected and into the glycolysis pathway um through ribulose 5 phosphate xyo 5 phosphate and into fructose 6 phosphate so there are some common steps where ribos 5 phosphate generated from nucleotide breakdown can actually be redirected the glycolysis pathway either for ATP generation or um for glucose generation so it's just important to note that as well guys um so again before I move on from this I wanted to just talk to you guys about a few different Roots this

um this glucose 6 phosphate can take so one that we mentioned was glucoses phosphate can actually be directed um down to rulos 5 phosphate you can generate a couple of NPH and it can be redirected back into the glycolysis pathway so that's one way it can actually um proceed now another way it can proceed is that glucose 6 can go down to rulis 5 phosphate again go um be converted into ribos 5 phosphate and then into prpp for nucleotide synthesis so that's another way it can be um redirected so there's a few different methods for

which um this pathway can proceed so I just want you guys to know that um the pathway can proceed in multiple directions depending on what the cell needs if the cell needs um the cell needs ATP um it can go back into the glycolysis pathway if it if it if it's going to create nucleotides um for nucleotide synthesis it'll go it'll get directed into prpp synthesis so um that's all I want you guys to know for now but um the main thing again is that this pathway generates NPH it generates two of them and it

also generates substrates for nucleotide synthesis so that's all I want you guys to know for now so now now that the pentos phosphate pathway actually generates nadph what is it actually needed for why is nadph so important well um as I mentioned before the uh nadph is necessary or um important for oxidative stress homeostasis now things um such as oxidant stress from drugs from from metabolism can create um hydrogen peroxide it can create superoxides it can create it can create U free radicals it can create um oxidative stress so how does the cell actually deal

with this well the cell deals with it by um by way of nadph now nadph um once it's generated from the pentoside pathway can actually be utilized by an enzyme Nuno known as glutathion reductase so glutathion reductase actually uh o oxidizes the nadph to nadp+ and in the meantime it'll actually reduce uh oxidize glutathion into reduced glutathion now once the cell has reduced glutathion it can take the glutathion um and utilize it um via the enzyme glutathion peroxidase um and in doing so it can actually reduce and actually process the hydrogen peroxide into two H2O

so it can actually process something that's something that's um potentially dangerous and toxic to the cell into something that's not so it can it can convert hydrogen peroxide into two water molecules so this is um the way a cell typically can actually reduce a lot of its oxidative stress by this mechanism so this mechanism is very important particularly in arthro sites or red blood cells so I just want to remember that guys this pathway is critical for erthrocytes so um now moving on to some of the problems that can happen if this enzyme or this

pathway is malfunctional and now one of the major malfunctions of this pathway is actually in its first step in its first enzyme so um deficiency of glucose 6 fos dehydrogenase can actually occur um so remember as I mentioned before glucose 6 phosphate dehydrogenase is the First Rate limiting step of the pentos phosphate pathway and in fact this deficiency um is so prevalent that it's one of the most prevalent um um genetic disorders in the world 7.5% of the world population is actually deficient in this enzyme um some areas of Africa are up to 35% prevalent

um or up to 35% um of the of the population in certain parts of Africa are actually deficient in this enzyme and there are some theories about why this is it could be that it um being deficient in this enzyme could be protective against malaria and this deficiency is an exlink recessive inheritance so typically males are the most affected by this uh this deficiency so being deficient in this enzyme may cause a few different um few different uh syndromes or symptoms one of them is htic anemia so as I mentioned before erthrocytes depend critically on

um the pendos pathway for nadph generation and uh oxidative stress capacity and um hemolytic anemia can occur um after several different things it can occur after ingestion of antimalarial medications it can occur um um after eating even after eating some fava beans called it's that the condition is called favism um it's just any type of um abnormal stress that can occur on the cell can actually cause a hemic anemia because the cells are a little more sensitive because they are in this enzyme and this may also cause um neonatal hyper bmia or neonatal jaundice now

um there's a physiological jaundice in um in neonatal period um that which is normal um there is a neonatal jaundice which is normal it's called physiologic jaundice and that occurs between two to three days of of birth or two to three days of age now if the baby is becoming um jaist with the first 24 hours of birth then you may want to check to see if this uh enzyme is deficient or not so um that is some of the main causes um could be due to um glucose 6 fos dehydrogenase deficiency anyways guys that

was a quick video on the pentos F pathway um I hope you guys found this video helpful if you did please like And subscribe for more videos like this one and as always thank you so much for watching and have a great day