Fructose Metabolism Disorders Overview

welcome back to dirty medicines dirty biochemistry series in this lesson we're going to be discussing the disorders of fructose metabolism the way that this video is going to work is first I'm going to walk you through the biochemical pathway whereby fructose is broken down and diverted into other substances at the end of the video we'll talk about two diseases that form if you lack certain enzymes in this pathway now just like the galactose lecture fructose is broken down in a very specific manner and if certain enzymes don't work you get two diseases one disease is on the more benign spectrum where there's very minor symptoms if any symptoms at all but the other disease is very significant and can be very severe throughout life so let's get started by first talking about the biochemical pathway so of course since we're talking about disorders of fructose metabolism we have to start with fructose so fructose gets converted into fructose one phosphate and the enzyme that catalyzes that conversion is called fructose kinase remember what kinase means guys and girls kinase means that a phosphate group gets added so if you start with fructose and the enzyme is fructose kinase four octo kinase really means fructose gets a phosphate added to it because that's what kinase means so look at the product its fructose with one phosphate stuck onto it so it's really easy to know what the reactant is and what the product is if you can work through the naming convention of the enzyme so fructose gets converted into fructose one phosphate by fructose kinase and then fructose one phosphate actually can take two different paths here now the enzyme that converts it into these two different paths is going to be the same and that enzyme is called aldolase be the two options where fructose one phosphate can choose which product it wants to become is glyceraldehyde and DHAP so dihydroxyacetone phosphate DHAP now collectively both glyceraldehyde and DHAP can come back to form the same product and that's glyceraldehyde 3-phosphate you may have heard this referred to as g3p and if you recognize g3p or if you've seen glyceraldehyde-3-phosphate before you've probably seen it as one of the entryways into glycolysis so this is the pathway as a whole fructose to fructose one phosphate fructose one phosphate to either glyceraldehyde or DHAP both glyceraldehyde and DHAP will be converted into g3p glyceraldehyde 3-phosphate and then once you have that glyceraldehyde-3-phosphate you can then enter glycolysis now let me pause for a second and point out a couple things which might help you make sense of this pathway and reason through it so if you look at fructose obviously fructose ends with O's OSE so you know it's some kind of carbohydrate you know that glucose goes through glycolysis to break down glucose right so any other carbohydrate can still get into glycolysis some way and what this pathway is showing you is the evidence of that so even if you're starting with fructose which is a completely different sugar then glucose you can still process it and break it into something in this case glyceraldehyde 3-phosphate which can ultimately enter glycolysis and then be broken down into products that will yield ATP so the bottom line here is that all carbohydrates will ultimately give you the energy that you need some just get broken down faster like in the case of dextrose and some get broken down slower like in the case of fructose so this is our pathway for fructose metabolism and how are you going to remember the order of this pathway well that's really high yield and I've given you an awesome dirty medicine pneumonic which I'm about to show you in order to memorize this so my little sentence here this little phrase that I say to help me remember what the fructose biochemical pathway is is that fruits are filled with fructose they are goddamn juicy and I spelled juicy with a G now what is this telling us well let's look at this the F in fruits corresponds to the F and fructose the F infilled corresponds to the F in fructose kinase the F in fructose corresponds to the F in fructose one phosphate so we're just going in order in terms of the high-yield reactant enzyme products react an enzyme product and we're gonna work our way down and the way that I've arranged the sentence on the slide is going to show you exactly which line were on so the first 3 FS for fructose fructose Kanye's fructose 1 philosophy now the a in our is the a in aldolase be goddamn the G in God is glyceraldehyde the D in dam is DHAP and in the mnemonic they're on the same line which tells you that glyceraldehyde and DHAP are on the same line since fructose one phosphate can go to either one of them on the same line and then the G and juicy tells us about the G in glyceraldehyde-3-phosphate so once again fruits are filled with fructose they are goddamn juicy and of course juicy is spelled with a G now in addition to telling you the order of the biochemical pathway of fructose metabolism this also tells you something else that you need to know about fructose if you don't already is that fruits juices and honey are the three sources with the highest concentration of fructose okay so fruits juices and honey so think about these kind of like juicy fruity sugary types of foods and drinks those all have fructose so fruits are filled with fructose they are goddamn juicy so here's our pathway and here's where we are so far at this point you should understand the biochemical pathway which is on the on the simpler side in the grand scheme of things we've seen some pathways in this session in this chapter of dirty medicine where they're much longer so this one isn't terribly difficult to learn and I've given you an awesome dirty medicine mnemonic to help you memorize it now we need to talk about the two high-yield diseases that occur if we knock out the two enzymes that you see in red text on this slide so the first is going to be a fructose kinase deficiency so if we knock out fructose kinase let's talk about what happens so in a fructose kinase deficiency you're gonna get fructose in the blood and the urine this is an autosomal recessive disease and it's pretty benign right nothing major is gonna happen here the symptoms will be pretty minor you might not even notice anything and once more let's look at our pathway here so if you knock out fructose kinase then you obviously cannot convert fructose into fructose one phosphate so you get this buildup of fructose and it's the buildup of fructose that's gonna spill into your blood and spill into your urine that's gonna give you fructose urea so urea means urine so fructose in the urine and fructose emia right amia means blood so fructose in the blood so that's where the fructose in the blood and the urine comes from now luckily having a ton of fructose in your blood in your urine is not really a huge deal so this is autosomal recessive and it's very benign so how do we remember this right it it's a fructose kinase deficiency so it's not terribly hard to remember that you're gonna get fructose urea and fructose emia but what you need to know is that this is a you know relatively benign condition compared to the next disease that we're going to talk about and that's the highest yield thing here because in clinical vignettes if they describe somebody who's not really experiencing a lot of symptoms then maybe they're pointing you in the direction of a fructose kinase deficiency so how do you know that right what's the mnemonic to memorize this well instead of saying fructose kinase deficiency I want you to say fructose kind a deficiency so instead of saying kind I want you to say kinda so this is like kind of benign it's like kind of a big deal but it's not really it's only kind of it's only it only kind of affects you right fructose kinase deficiency kinda so this is kind of benign all right that is a fructose kinase deficiency so that's the benign one right just like in the galactose lecture we had one of the disease's being really benign and the other disease being really severe so now we're gonna transition and talk about the severe one so the only other enzyme that you see on this slide is aldolase B so the next disease is you know if you couldn't guess it's gonna be an outer lace B deficiency so we knockout outta lace B and we can't convert fructose one phosphate into either glyceraldehyde or DHAP so we can't do anything shown there in the blue dotted line right so if we can't do that we can't form glyceraldehyde we can't form DHAP but you're gonna get a buildup of fructose one phosphate okay so this is an outer lace B deficiency now sometimes a delay speed deficiency is actually referred to by a different name so if you see it referred to as a hereditary fructose intolerance it's the same thing right so hereditary fructose intolerance a delays v deficiency same thing so the pathophysiology here as you see on this slide is a knockout of a delays be depicted here by the light blue x mark next to a delays B and what's happening is that you're building up fructose one phosphate so I'm gonna put the little pathway here on the corner of this slide just to show you something that's going to be incredibly high yield so in this step that converts fructose to fructose one phosphate I left out one part that I didn't explain to you yeah and I saved it for this slide in order to help make the most sense of it so when you convert fructose to fructose one phosphate you actually need to use ATP and in that step you're converting ATP into right so there's three phosphates and ATP but there's only two phosphates in ADP and so where does that third phosphate go well that third phosphate is being attached to fructose by fructose kinase so remember fructose kinase kinase means puts a phosphate on fructose that's what fructose kinase means so where does that phosphate come from what's coming from ATP so this is really important here because if you have an outer lace P deficiency then what that means is you're forming fructose one phosphate but it's not going anywhere so in the body fructose one phosphate is being formed and formed and formed and formed and what that means is you're depleting ATP because in order to form fructose one phosphate you have to strip a phosphate off ATP so you're using up a ton of ATP so what happens if you're using up ATP but never doing anything with the product that you're forming well without energy right without ATP we can't do gluconeogenesis and we can't do glyco general lysis so not only are we burning ATP forming this fructose one phosphate but can't go anywhere because aldolase V is like sorry I don't work for this one phosphates building up ATP is depleting the body is gonna need ATP in order to do gluconeogenesis and glycogenolysis but because it doesn't have any because ATP is just completely spent forming this fructose one phosphate then you can't do gluconeogenesis you can't do glycogenolysis and guys what happens if you can't do those two pathways low blood sugar hypoglycemia so you're gonna get an increase in hypoglycemia which is to say that more often you will have low blood glucose okay so look at look at this here we're talking about a disease called hereditary fructose intolerance and the reason that it's named hereditary fructose intolerance is because if you don't have the enzyme aldolase b then when you put fructose into the system right so when the person with this disease drinks juice drinks or eats honey or has a fruit with this fructose in it then there's fructose in the body that gets converted to fructose one phosphate but then the fructose one phosphate can't go anywhere so the person's intolerant of fructose because you building up and building up and building up fructose one phosphate burning ATP burning ATP burning ATP can't do gluconeogenesis or glycogenolysis which means you can't raise blood glucose which means when somebody has a fruit a juice or honey they're gonna have hypoglycemic events okay so I just put the whole picture together for you I hope that you were able to follow that so obviously if you're intolerant of fructose hence the name hereditary fructose intolerance the treatment here is pretty simple it's don't eat fructose right but in addition to fructose you also can't have glucose or sucrose because they can convert themselves into fructose and cause this to happen as well so I'm gonna summarize this one more time because it's the most high-yield disease that we're talking about in this lesson and if you're tired of hearing it or you already know it then fast forward but once more hereditary fructose intolerance is a disease that is due to an elderly speed efficiency because aldolase be doesn't work you have a buildup of fructose one phosphate that can't be converted into anything else but the body doesn't know that it's just gonna keep making fructose one phosphate and in doing so it's burning up all the ATP that the body has available and because it's burning up the ATP then gluconeogenesis and glycogenolysis cannot use ATP because there's none left which means you can't raise blood glucose so in the presence of fructose you get hypoglycemic events that's the high yield here so don't eat fructose don't eat glucose don't eat sucrose that's how you treat this so how do you remember everything that I just talked about here's the dirty medicine mnemonic so the disease is called hereditary fructose intolerance and I want you to pay attention to the here in hereditary the fruit in fructose and the int in intolerance and I want you to say here you are entirely so a fructose kinase deficiency was fructose kind a ACE deficiency it's like kind of a big deal but you know not really but here you are entirely you are absolutely that is to say you are so here you are entirely here for hereditary front for fructose and int for intolerance or here if you have this disease if you have the auto lease fee deficiency here you are fret entirely so those are our two diseases now let's summarize them on this slide to really drive home what you need to know I really I'm a big fan of summarizing and making these concepts perfectly crystal clear so we have fructose kinase deficiency and we have hereditary fructose intolerance the first one is due to a knockout of fructose kinase as the name implies and the second one is due to a deficiency of aldolase B now the high yields and the first disease was that it was benign and it was autosomal recessive and in the second disease we talked about that you get these hypoglycemic events which are due to a decrease of ATP after you ingest fruits juices or honeys our mnemonics were for a fructose kinase efficiency fractal kindness deficiency kinda it's right it's like kind of benign not a big deal and her hereditary fructose intolerance here you are entirely because if you eat fructose or glucose or sucrose and you get these hypoglycemic events because there's no ATP available so guys that is it for the disorders of fructose metabolism know these diseases know their pathophysiology know the high-yield associations and above all else know the dirty medicine mnemonic because it's going to give you the points on test day

welcome back to dirty medicines dirty biochemistry series in this lesson we're going to be discussing the disorders of fructose metabolism the way that this video is going to work is first I'm going to walk you through the biochemical pathway whereby fructose is broken down and diverted into other substances at the end of the video we'll talk about two diseases that form if you lack certain enzymes in this pathway now just like the galactose lecture fructose is broken down in a very specific manner and if certain enzymes don't work you get two diseases one disease is on the more benign spectrum where there's very minor symptoms if any symptoms at all but the other disease is very significant and can be very severe throughout life so let's get started by first talking about the biochemical pathway so of course since we're talking about disorders of fructose metabolism we have to start with fructose so fructose gets converted into fructose one phosphate and the enzyme that catalyzes that conversion is called fructose kinase remember what kinase means guys and girls kinase means that a phosphate group gets added so if you start with fructose and the enzyme is fructose kinase four octo kinase really means fructose gets a phosphate added to it because that's what kinase means so look at the product its fructose with one phosphate stuck onto it so it's really easy to know what the reactant is and what the product is if you can work through the naming convention of the enzyme so fructose gets converted into fructose one phosphate by fructose kinase and then fructose one phosphate actually can take two different paths here now the enzyme that converts it into these two different paths is going to be the same and that enzyme is called aldolase be the two options where fructose one phosphate can choose which product it wants to become is glyceraldehyde and DHAP so dihydroxyacetone phosphate DHAP now collectively both glyceraldehyde and DHAP can come back to form the same product and that's glyceraldehyde 3-phosphate you may have heard this referred to as g3p and if you recognize g3p or if you've seen glyceraldehyde-3-phosphate before you've probably seen it as one of the entryways into glycolysis so this is the pathway as a whole fructose to fructose one phosphate fructose one phosphate to either glyceraldehyde or DHAP both glyceraldehyde and DHAP will be converted into g3p glyceraldehyde 3-phosphate and then once you have that glyceraldehyde-3-phosphate you can then enter glycolysis now let me pause for a second and point out a couple things which might help you make sense of this pathway and reason through it so if you look at fructose obviously fructose ends with O's OSE so you know it's some kind of carbohydrate you know that glucose goes through glycolysis to break down glucose right so any other carbohydrate can still get into glycolysis some way and what this pathway is showing you is the evidence of that so even if you're starting with fructose which is a completely different sugar then glucose you can still process it and break it into something in this case glyceraldehyde 3-phosphate which can ultimately enter glycolysis and then be broken down into products that will yield ATP so the bottom line here is that all carbohydrates will ultimately give you the energy that you need some just get broken down faster like in the case of dextrose and some get broken down slower like in the case of fructose so this is our pathway for fructose metabolism and how are you going to remember the order of this pathway well that's really high yield and I've given you an awesome dirty medicine pneumonic which I'm about to show you in order to memorize this so my little sentence here this little phrase that I say to help me remember what the fructose biochemical pathway is is that fruits are filled with fructose they are goddamn juicy and I spelled juicy with a G now what is this telling us well let's look at this the F in fruits corresponds to the F and fructose the F infilled corresponds to the F in fructose kinase the F in fructose corresponds to the F in fructose one phosphate so we're just going in order in terms of the high-yield reactant enzyme products react an enzyme product and we're gonna work our way down and the way that I've arranged the sentence on the slide is going to show you exactly which line were on so the first 3 FS for fructose fructose Kanye's fructose 1 philosophy now the a in our is the a in aldolase be goddamn the G in God is glyceraldehyde the D in dam is DHAP and in the mnemonic they're on the same line which tells you that glyceraldehyde and DHAP are on the same line since fructose one phosphate can go to either one of them on the same line and then the G and juicy tells us about the G in glyceraldehyde-3-phosphate so once again fruits are filled with fructose they are goddamn juicy and of course juicy is spelled with a G now in addition to telling you the order of the biochemical pathway of fructose metabolism this also tells you something else that you need to know about fructose if you don't already is that fruits juices and honey are the three sources with the highest concentration of fructose okay so fruits juices and honey so think about these kind of like juicy fruity sugary types of foods and drinks those all have fructose so fruits are filled with fructose they are goddamn juicy so here's our pathway and here's where we are so far at this point you should understand the biochemical pathway which is on the on the simpler side in the grand scheme of things we've seen some pathways in this session in this chapter of dirty medicine where they're much longer so this one isn't terribly difficult to learn and I've given you an awesome dirty medicine mnemonic to help you memorize it now we need to talk about the two high-yield diseases that occur if we knock out the two enzymes that you see in red text on this slide so the first is going to be a fructose kinase deficiency so if we knock out fructose kinase let's talk about what happens so in a fructose kinase deficiency you're gonna get fructose in the blood and the urine this is an autosomal recessive disease and it's pretty benign right nothing major is gonna happen here the symptoms will be pretty minor you might not even notice anything and once more let's look at our pathway here so if you knock out fructose kinase then you obviously cannot convert fructose into fructose one phosphate so you get this buildup of fructose and it's the buildup of fructose that's gonna spill into your blood and spill into your urine that's gonna give you fructose urea so urea means urine so fructose in the urine and fructose emia right amia means blood so fructose in the blood so that's where the fructose in the blood and the urine comes from now luckily having a ton of fructose in your blood in your urine is not really a huge deal so this is autosomal recessive and it's very benign so how do we remember this right it it's a fructose kinase deficiency so it's not terribly hard to remember that you're gonna get fructose urea and fructose emia but what you need to know is that this is a you know relatively benign condition compared to the next disease that we're going to talk about and that's the highest yield thing here because in clinical vignettes if they describe somebody who's not really experiencing a lot of symptoms then maybe they're pointing you in the direction of a fructose kinase deficiency so how do you know that right what's the mnemonic to memorize this well instead of saying fructose kinase deficiency I want you to say fructose kind a deficiency so instead of saying kind I want you to say kinda so this is like kind of benign it's like kind of a big deal but it's not really it's only kind of it's only it only kind of affects you right fructose kinase deficiency kinda so this is kind of benign all right that is a fructose kinase deficiency so that's the benign one right just like in the galactose lecture we had one of the disease's being really benign and the other disease being really severe so now we're gonna transition and talk about the severe one so the only other enzyme that you see on this slide is aldolase B so the next disease is you know if you couldn't guess it's gonna be an outer lace B deficiency so we knockout outta lace B and we can't convert fructose one phosphate into either glyceraldehyde or DHAP so we can't do anything shown there in the blue dotted line right so if we can't do that we can't form glyceraldehyde we can't form DHAP but you're gonna get a buildup of fructose one phosphate okay so this is an outer lace B deficiency now sometimes a delay speed deficiency is actually referred to by a different name so if you see it referred to as a hereditary fructose intolerance it's the same thing right so hereditary fructose intolerance a delays v deficiency same thing so the pathophysiology here as you see on this slide is a knockout of a delays be depicted here by the light blue x mark next to a delays B and what's happening is that you're building up fructose one phosphate so I'm gonna put the little pathway here on the corner of this slide just to show you something that's going to be incredibly high yield so in this step that converts fructose to fructose one phosphate I left out one part that I didn't explain to you yeah and I saved it for this slide in order to help make the most sense of it so when you convert fructose to fructose one phosphate you actually need to use ATP and in that step you're converting ATP into right so there's three phosphates and ATP but there's only two phosphates in ADP and so where does that third phosphate go well that third phosphate is being attached to fructose by fructose kinase so remember fructose kinase kinase means puts a phosphate on fructose that's what fructose kinase means so where does that phosphate come from what's coming from ATP so this is really important here because if you have an outer lace P deficiency then what that means is you're forming fructose one phosphate but it's not going anywhere so in the body fructose one phosphate is being formed and formed and formed and formed and what that means is you're depleting ATP because in order to form fructose one phosphate you have to strip a phosphate off ATP so you're using up a ton of ATP so what happens if you're using up ATP but never doing anything with the product that you're forming well without energy right without ATP we can't do gluconeogenesis and we can't do glyco general lysis so not only are we burning ATP forming this fructose one phosphate but can't go anywhere because aldolase V is like sorry I don't work for this one phosphates building up ATP is depleting the body is gonna need ATP in order to do gluconeogenesis and glycogenolysis but because it doesn't have any because ATP is just completely spent forming this fructose one phosphate then you can't do gluconeogenesis you can't do glycogenolysis and guys what happens if you can't do those two pathways low blood sugar hypoglycemia so you're gonna get an increase in hypoglycemia which is to say that more often you will have low blood glucose okay so look at look at this here we're talking about a disease called hereditary fructose intolerance and the reason that it's named hereditary fructose intolerance is because if you don't have the enzyme aldolase b then when you put fructose into the system right so when the person with this disease drinks juice drinks or eats honey or has a fruit with this fructose in it then there's fructose in the body that gets converted to fructose one phosphate but then the fructose one phosphate can't go anywhere so the person's intolerant of fructose because you building up and building up and building up fructose one phosphate burning ATP burning ATP burning ATP can't do gluconeogenesis or glycogenolysis which means you can't raise blood glucose which means when somebody has a fruit a juice or honey they're gonna have hypoglycemic events okay so I just put the whole picture together for you I hope that you were able to follow that so obviously if you're intolerant of fructose hence the name hereditary fructose intolerance the treatment here is pretty simple it's don't eat fructose right but in addition to fructose you also can't have glucose or sucrose because they can convert themselves into fructose and cause this to happen as well so I'm gonna summarize this one more time because it's the most high-yield disease that we're talking about in this lesson and if you're tired of hearing it or you already know it then fast forward but once more hereditary fructose intolerance is a disease that is due to an elderly speed efficiency because aldolase be doesn't work you have a buildup of fructose one phosphate that can't be converted into anything else but the body doesn't know that it's just gonna keep making fructose one phosphate and in doing so it's burning up all the ATP that the body has available and because it's burning up the ATP then gluconeogenesis and glycogenolysis cannot use ATP because there's none left which means you can't raise blood glucose so in the presence of fructose you get hypoglycemic events that's the high yield here so don't eat fructose don't eat glucose don't eat sucrose that's how you treat this so how do you remember everything that I just talked about here's the dirty medicine mnemonic so the disease is called hereditary fructose intolerance and I want you to pay attention to the here in hereditary the fruit in fructose and the int in intolerance and I want you to say here you are entirely so a fructose kinase deficiency was fructose kind a ACE deficiency it's like kind of a big deal but you know not really but here you are entirely you are absolutely that is to say you are  so here you are entirely here for hereditary front for fructose and int for intolerance or here if you have this disease if you have the auto lease fee deficiency here you are fret entirely so those are our two diseases now let's summarize them on this slide to really drive home what you need to know I really I'm a big fan of summarizing and making these concepts perfectly crystal clear so we have fructose kinase deficiency and we have hereditary fructose intolerance the first one is due to a knockout of fructose kinase as the name implies and the second one is due to a deficiency of aldolase B now the high yields and the first disease was that it was benign and it was autosomal recessive and in the second disease we talked about that you get these hypoglycemic events which are due to a decrease of ATP after you ingest fruits juices or honeys our mnemonics were for a fructose kinase efficiency fractal kindness deficiency kinda it's right it's like kind of benign not a big deal and her hereditary fructose intolerance here you are entirely because if you eat fructose or glucose or sucrose and you get these hypoglycemic events because there's no ATP available so guys that is it for the disorders of fructose metabolism know these diseases know their pathophysiology know the high-yield associations and above all else know the dirty medicine mnemonic because it's going to give you the points on test day

Transcript for:Fructose Metabolism Disorders Overview

Transcript for:
Fructose Metabolism Disorders Overview