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

hey everyone Nessa Simon talked to you guys about the pentose phosphate pathway or otherwise known as the pentose 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 this pathway the most and finally I've talked to you guys about some problems that can occur if this pathway doesn't operate correctly 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 does it operate correctly so to begin what is the pentose phosphate pathway well the pathway is also known as the hexose monophosphate shunt it occurs in virtually all cell types and tissues one of the main utilizers of the pathway is the liver which utilizes 30% of his glucose for the pentose phosphate pathway other tissues that utilize this pathway quite a bit are the red blood cells to maintain oxidative capacity the liver also utilizes this pathway to to protect itself against oxidative stress due to drug metabolism and some of the tissues that don't utilize this pathway so much or include muscles muscles don't utilize this pathway so much this pathway occurs in the cytoplasm it produces NADPH now NADPH is very necessary for several pathways one includes fatty acid synthesis 50% of NADPH typically goes to fatty acid synthesis again as I mentioned before NADPH is necessary for oxidative stress homeostasis so this is why we see the liver in red blood cells using the pathway they do so to generate NADPH to protect themselves against oxidative stress and NADPH is also important for cytochrome p450 enzymes and this is again important in the liver this pentose phosphate pathway also produces trioses hexoses and pentoses and pentoses are necessary for nucleotide synthesis so where does this all begin well the pathway actually begins near the beginning of glycolysis pathway with glucose 6-phosphate so what happens is instead of glucose 6-phosphate going down the glycolysis pathway it gets shunted into another pathway by the enzyme glucose phosphate dehydrogenase so glucose Fog leuco six phosphate dehydrogenase converts glucose 6-phosphate to gluco no.15 lactone six phosphate and in doing so it actually takes an nadp+ and reduces it to an ad pH now this step of the pentose phosphate pathway is actually the rate limiting step and NADPH the product of this step actually inhibits the enzyme low levels of NADPH can actually act eight this enzyme as well so once you have gluco no.15 lactone six phosphate this can actually be converted into six faso gluconate which then can be inverted into ribulose 5-phosphate and this is done by the enzyme six faso gluconate dehydrogenase and again in this step nadp+ is actually reduced to NADPH so this is again another important step of the pathway so for this pathway guys I want you to remember that the the first and the third step of the pathway are the ones that generate NADPH and I want you guys to try to remember these two enzymes now once you have ribulose 5-phosphate it can do a couple of different things one it can actually get converted to xylose five phosphate by ribulose phosphate three epimer a's and then the xylose five phosphate can actually be redirected back into the glycolysis pathway by getting converted into fructose 6-phosphate by trans key delays so once once the cell kind of generates its NADPH it can actually redirect its its end product back into the glycolysis pathway so that the the cell can actually generate ATP from from that substrate so this is it's incredibly clever how the cell can actually do this if it needs NADPH it can just redirect it into the pentose phosphate pathway and then back to the glycolysis pathway to get some ATP from it as well another way or another thing that the ribulose 5-phosphate can do is it can actually be converted into ribose 5-phosphate by ribose phosphate isomerase enzyme once you generate ribose 5-phosphate it can actually be converted into five fossil obviously one pyrophosphate or prpp now this is the this is the molecule I want you guys remember this molecule is very very important in medicine and we always want to know this because this molecule we can direct can be directed into permitting or purine synthesis so this is the molecule that really determines permitting and purine synthesis for cells so PRPP remember that guy's five phosphorus l1 pyrophosphate so now that you guys know the importance of prpp for permitting empyrion synthesis now what can happen is in cells that have nucleotides this the nucleotides can have to be broken down into ribose 5-phosphate now ribose 5-phosphate can be converted into back into some of these earlier steps so I show these arrows as one directional but a lot of these are reversible so what can happen is ribose 5-phosphate can actually redirected and into the glycolysis pathway through ribulose 5-phosphate xylose five phosphate and into fructose 6-phosphate so there are some common steps were ribose 5-phosphate generated from nucleotide breakdown can actually redirect lead into glycolysis pathway either for ATP generation or for glucose generation so it's just important to note that as well guys so again before I move on from this I want to just talk to you guys about a few different routes this this glucose 6-phosphate can take so one that we mentioned was glucose 6-phosphate can actually be directed down to ribulose 5-phosphate you can generate a couple of NADPH and it can be redirected back into the glycolysis pathway so that's one way it can actually proceed now another way can proceed is that glucose 6-phosphate can go down to ribulose 5-phosphate again go be converted into right was 5-phosphate er than into prpp for nucleotide synthesis so that's another way it can be redirected so there's a few different methods for which this pathway can proceed so I just want you guys to know that the pathway can proceed in multiple directions depending on what the cell needs if the cell needs the cell needs ATP it can go back into the glycolysis pathway if it if it if it's going to create nucleotides for nucleotide synthesis it'll go it'll get directed into PRPP synthesis so that's all I want you guys to know for now but the main thing again is that this pathway generates NADPH 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 pentose phosphate pathway actually generates NADPH what is it actually needed for why is NADPH so important well as I mentioned before the NADPH is necessary or important for oxidative stress homeostasis now things such as oxidant stress from drugs from from metabolism can create hydrogen peroxide and can create super oxides it can create it can create free radicals they can create oxidative stress so how does that cell actually deal with this well the cell deals with it by by way of NADPH now NADPH once it's generated from the pentose phosphate pathway can actually be utilized by an enzyme known as known as glutathione reductase so Athene reductase actually oxidizes the NADPH to nadp+ and in the meantime it'll actually reduce oxidized glutathione in to reduce glutathione now once the cell has a reduced glutathione it can take the glutathione and utilize it by the enzyme glutathione peroxidase in in doing so it can actually reduce and actually process the hydrogen peroxide into to h2o so it can actually process something that's something that's potentially dangerous and toxic to the cell into something that's not so we can they can convert hydrogen peroxide into two water molecules so this is 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 erythrocytes or red blood cells so I just want to remember that guys this pathway is critical for erythrocytes so now moving on to some of the problems that what that can happen if this enzyme or this pathway is malfunctioning and now one of the major malfunctions of those pathways actually in its first step in its first enzyme so deficiency of glucose 6-phosphate dehydrogenase can actually occur so remember as I mentioned before glucose 6-phosphate dehydrogenase is the first rate limiting step of the pentose phosphate pathway and in fact this deficiency is so prevalent that it's one of the most prevalent genetic disorders in the world at seven point five percent of the world population is actually deficient in this enzyme some areas of africa are up to 35% prevalent or up to 35% 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 being deficient in this enzyme could be protective against malaria and this deficiency is an x-linked recessive inheritance so typically males are the most affected by this distance II so being deficient in this enzyme may cause a few different few different syndromes or symptoms one of them is a melodic anemia so as I mentioned before erythrocytes depend critically on the pentose phosphate pathway for NADPH generation and oxidative stress capacity and hemolytic anemia can occur after several different things and can occur after ingestion of anti-malarial medications it can occur after eating even after eating some fava beans call it's that the conditions called fav ism it's just any type of abnormal stress that can occur on the cell can actually cause a hemolytic anemia because the cells are a little more sensitive because they are deficient in this enzyme and this may also cause neonatal hyperbilirubinemia or neonatal jaundice now there's a physiological jaundice in in neonatal period that which is normal there is neonatal jaundice which is normal it's called physiologic jaundice and that occurs between two to three days of birth or two to three days of age now if the baby is becoming jaundiced within the first 24 hours of birth then you may want to check to see if this enzyme is deficient or not so that is some of the main causes could be due to glucose 6-phosphate dehydrogenase deficiency anyways guys that was a quick video on the pentose phosphate pathway 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

Channel: JJ Medicine

Views: 144,419

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Keywords: Pentose phosphate pathway, hexose monophosphate shunt, pentose phosphate shunt, NADPH pentose phosphate pathway, glucose 6 phosphate dehydrogenase, erythrocytes NADPH, pentose phosphate pathway regulation, pentose phosphate pathway activation, pentose phosphate pathway inhibition, purpose of the pentose phosphate pathway, pentose phosphate pathway lesson, JJ Medicine, pentose phosphate pathway mechanism, pentose phosphate pathway health, pentose phosphate pathway animation

Id: bgu3_WJY62w

Length: 12min 26sec (746 seconds)

Published: Fri Apr 07 2017