Amino Acid Metabolism Part II

okay we're going to look at the second part of amino acid metabolism so we'll look at digestion protein turnover our Ura cycle amino acid catabolism and some of our errors in amino acid metabolism all right so all for all of protein synthesis all essential amino acids must be available to the cell so that means before we can even start making a protein we have to have all 20 of our amino acids so if we have a limiting amino acid so we do not have a lot of it we're going to slow down protein synthesis or even halt it depending on how limiting it is and then if we get inadequate energy consumption so we're not let's say we're not getting enough um glucose or our main energy source or lipids in our diet then we're also going to limit protein synthesis so we if we have a a too little amount of an amino acid that we need we're going to slow it down if it's very low levels of that amino acid we're going to stop synthesis and if we don't have enough energy to make anything then we're going to um limit our protein synthesis as well and this makes sense because if you're not getting enough energy in your diet then you don't want to be making new proteins all right so we've got two different types of proteins one is called an incomplete protein and one is a complete protein so an incomplete protein just means that it had doesn't have all of the essential amino acids so not that it doesn't have all 20 amino acids just it doesn't have all of the essential amino acids and then a complete prot protein is what we call a high quality protein and that will have sufficient amounts of all of our nine essential amino acids so any of our animal uh proteins will have will be complete proteins and also soy proteins other sources of complete proteins if you are a vegetarian would include a quinoa that would be a complete protein or chia seed would also be a complete protein all right so um in order to get our proper amount of protein in the diet we can do two different things we can have mutual supp mentation or we could have complim um complimentary proteins uh so this Mutual supplementation would be to combine two or more incomplete protein sources to make a complete protein uh so we can do this um when we combine two or more foods to make all nine of our essential amino acids so mutual supplementation would be combining to incomplete protein sources and then the two protein sources that would um be mutual supplementations of each other are called complimentary proteins so here's some examples here so for instance if we're looking at legumes legumes do not have enough methionine or cysteine in them however grains nuts and seeds are high in methionine and cysteine so you could do a complimentary food combination with a legume and a grain Nutter seed so for instance rice and lentils red beans and rice rice and blackeyed peas um hummus so hummus will have garbanzo beans and sesame seeds in them so these would be where we have complimentary food combinations that will get us all of the our limiting amino acids so you can see grains are limited in lysine but legumes are high in lysine so peanut butter and bread barley and lentil soup corn tortilla and beans would be examples of a complimentary food combination so many of our vegetables are going to be limited in lysine methionine and seene so our legumes again are um going to have lysine in them and then our grains nuts and seeds will have methionine and cysteine so to U and broccoli with almonds spinach salad with pine nuts and K kidney beans all of these will be examples of how we can make these complimentary food combinations to get all of our essential amino acids all right so let's look a little bit at our protein digestion so this is going to make uh happen mainly in our stomach and so we'll have proteases in our stomach that will cleave our peptide bonds to give us take all of those proteins and give us amino acids and small oligopeptides so you can see here um we have our stomach and so we've got pepsin pepsinogen these are going to be enzymes that are going to be breaking apart our our peptide bonds and then we go to our uh small intestine here uh I guess technically we go through our large intestine and then our small intestine but in our small intestine then we're going to have other um bacteria that can digest some of the other proteins for us as well so then these U amino acids will get absorbed into our bloodstream right so our dadum will secrete these interop peptidase so this would be a protease and that is going to be released from our pancreas to help us break down some of our amino acids and uh so it'll break down different types so uh we can take TR cinogen and take that to Tron using interop peptidase um and then Tron is an enzyme so this is a pro-enzyme we're converting it into Tron uh Tron can then uh activate kimot tripsin it will also activate elastase and carboxypeptidase actually for fun information carboxypeptidase elastase um and choton are all also Metallo enzymes so you're using metals to break up these peptide bonds uh so you can see elastase um will'll take a polypeptide and break it up into polypeptide fragments um sorry so we elastase choton and carboxy peptidase they all do the same thing which is break apart different polypeptides but they do this at different amino acids so we used this in chapter 6 when we took a sequence um a protein sequence and we cleaved it with different um peptidases in order to see what amino acids that we had all right so for n what we're aiming for is to get what we call nitrogen balance and that means that the nitrogen that we consume in our food is equal to the N nitrogen that we excrete in our urine uh so our waste product for our nitrogen is a molecule called Ura and that's what makes your PE stink so uh a typical normal healthy adult will need about 400 grams of protein per day to maintain nitrogen balance and obviously that depends on your size metabolism Etc and so go ahead and think what what points in your life would you want to have a positive nitrogen balance where you would want the amount of nitrogen that you consume to be greater than the nitrogen that you excrete uh so some examples of a positive nitrogen balance would be if you are pregnant so you're going to be creating um a new person so you need to make sure that you have more nitrogen going out than you're getting rid of because you're using that nitrogen uh points in your life when you might have a negative nitrogen balance would be um periods of fasting or starvation possibly even sickness all right so there are of course examples of people with extreme protein energy malnutrition so two of the most um uh visible are marasmus and Kashi oror so marasmus you're going to have in quate intake of protein and all other nutrients uh so this is both a protein malnutrition and energy malnutrition so not enough lipids and N enough carbohydrates uh you get a wasting and the weakening of the muscles and that includes the heart because you're using all of the muscles in order to uh in order to to sustain life and eventually you'll die from Death from dehydration heart failure or infection uh because we're not able to make any of our antibodies that we need our heart start starts to weaken as we're we're using it for energy uh in quashi or cor um this is a gan word that means the stick the sickness that the baby gets when the new baby comes uh so in this case they're getting sufficient calories but their calories are from only carbohydrate sources so they're getting insufficient protein in their diet but still sufficient energy in their diet um but we still will see muscle wasting and we'll also see EMA so here is some example of of what this looks like so again marasmus it's going to be characterized by stunted growth uh depressed metabolism uh you want to slow down the energy consumption as much as possible uh to try to maintain life as long as possible uh you're going to have a very low body temperature because you're not going to be um going creating a lot of energy in general um you'll start to deteriorate your intestinal lining you'll have stuned brain development and anemia so these are the the the children where you can see their ribs um and it's they General wasting away um they do not grow very big and they have very stunted brain development um so you'll see that they still have normal hair and they have what is described as an old man's face uh and then one of the key ways that we can differentiate between marasmus and um quasi oror is that in marasmus we'll see no edema in quasi oror this is where we see these children with these distended bellies um so we'll get some retention of body fat remember that um they're still getting some sufficient calories in their diet um but because they're not getting enough protein there will be [ __ ] growth [ __ ] development um so slowed growth and development and then because of the fact that they have a lack of protein in their diets they'll also suffer from edema so edema is where you get the water and so you can see examples of Edema here and these bellies as well um this is where you don't have the proteins to maintain your fluid balance so your cells can't hold in water um so your cells can't hold in water so the water will just pull in places where it shouldn't be you'll see a loss of appetite you'll get these um hair changes so dry brittle brittle hair uh lots of sores and in general sadness and apathy uh for marasmus these these um people don't apparently seem to even understand what's happening to them to the level where they don't have this um misery or sadness or apathy about them that the kashor core people do okay so let's then talk about how our amino acids can be turned into energy so how do we break down our proteins to turn it into energy uh so we're going to take our cellular proteins our dietary proteins and we're going to break them down into amino acids so that's the first thing that we have to do is break everything down into amino acids we're going to take this ammonia um from the amino acid and we can turn this into other amino acids we saw that in the last video we can turn it into nucleotides other biological Ames um or we can convert it to carbo phosphate which we see which will then go through our Ura cycle and create Ura then our carbon skeleton that can be taken and depending on the amino acid that we are using it can be taken to the citric acid cycle it could be made into pyate or oxel acetate or it could be made into acetal koay so we can take these amino acids and get directly ATP we could get glucose or could get fatty acids and Ketone bodies so uh what does the Ura cycle accomplish for the organism so it's going to provide an effective me uh mechanism to remove excess nitrogen from the body I the Ura will be synthesized in the liver and then exported to the kidneys where it will then go to your bladder so we're going to take the ammonium ion we're going to take some bicarbonate aspartate and 3 ATP and make Ura Fumarate and then 2 ADP so our key enzymes carban oil phosphate synthetase 1 so that's going to be our committed step um so we're going to take our amino acids and we're going to be doing aminotransferase reactions our goal is to get all of our amino acids into glutamate uh so we'll take our glutamine that we have and we'll take that ammonia and make ammonium ion from that and that ammonium ion will go to make carbano phosphate which will go into our Ura cycle and then our glutamates will use this aspartate aminotransferase so we can see we've got oxaloacetate here to um transfer this ammonium group to oxaloacetate to make aspartate then aspartate and carbano phosphate we'll be going into our Ura cycle so here is our Ura cycle we've got our carb oil phosphate so that's that nitrogen um and here this blue box is representing orane and um so this this molecule here will have ornithine and carban oil phosphate on it then we'll add in aspartate so here is aspartate here and so this is the nitrogen here from the aspartate amino acid here is our Alpha carbon our carboxy group our side chain from aspartate um through a series of reactions then we'll release Fumarate uh so we know Fumarate can go into our citric acid cycle and then now we've got here this Arginine so we've got ornithine with uh carbon with two nitrogens on it and then we will uh release this to make Ura and then we'll have ornithine remaining and then we can continue through this cycle so you can see we put in a carban oil phosphate with a nitrogen we put in um an aspartate with a nitrogen and we get out Fumarate with no nitrogens and Ura with two nitrogens so here's just another view of that exact same process but this time showing you the structure of ornithine so here's ornithine here will get transported into the mitochondrial Matrix will combine with carbano phosphate um and then through a series of reactions then uh that we're going to use ATP we'll get out this um we'll put in our aspartate molecule here and now we have this new molecule that has aspartate which is here that nitrogen um from carban oil phosphate there and then this is our ornithine group we release the Fumarate which is from our aspartate and then now these two nitrogens that are attached to our orine um will get hydrolized with water to make Ura and release that ornithine so this is just the structural view of this slide here showing you what this blue box looks like all right so our Ura cycle um we're including um this pyrro phosphate reaction we are going to use three high energy phosphate bonds so this is essentially three ATP equivalents for every Ura that's synthesized so I'll point that out to you here so first um this carbano phosphate has a high energy Bond we're releasing a phosphate this bond is a high energy Bond so that would be one ATP equivalent our second is here when we actually use ATP and then our third we're going to take a sparate and take it into a& um and so that will also uh you can see we're using this um& intermediate that will also be a high energy bond that we're breaking so we're using the equivalent of 3 ATP to make one Ura right so that Fumarate that we get um from our citric or sorry from our Ura cycle so here's the Fumarate that is made from our Ura cycle is then converted into malate malate is transported into the Matrix of the cell and then malate is turned into oxaloacetate and that oxaloacetate can be used for citric acid cycle or we could take that oxaloacetate if we needed to and convert it into aspartate and then use that aspartate to further fuel the Ura cycle all right so we also could have um enzyme deficiencies in our Ura cycle um so Aros oxinate is soluble and can be excreted in the urine uh so that is this molecule here uh so if for some reason we are not able to complete our Ura cycle we just don't release our um in our urine Ura we instead release this arinos seexan that's excreted in the urine one of the ways that you can tell that you have um someone who has this deficiency is they'll have a high amount of arginine in their diet or sorry they'll need to ingest high amounts of arginine in order to make this Ura cycle go since it's missing the capability of turning turning this AR arginosuccinate into Arginine so that would be how to fix it if you were someone who had this deficiency all right so our degradation of our amino acids leads to two different types of amino um precursors uh one we call our glucogenic and the other one we call our ketogenic uh so our I'll go to the next slide because we've got actually some pictures here so all of the ones that are blue are ones that we consider glucogenic um because we're taking these amino acids and turning them into something that could be achieved using uh glycolysis so pyruvate and citric acid cycle intermediates uh the ones that are ketogenic are going to be the ones that are turned into molecules um essentially aceto COA and aceto acetate that are mainly used in our ketogenesis right so now let's look at some errors in our amino acid metabolism H so one of the ones uh that's I wouldn't say common but is is very common in textbooks uh is this pheno keto um ketona so PKU and an individual that has this does not have the enzyme or has a deficiency or a um a mutation in the enzyme for pheny alanine hydroxy such that it doesn't work and so that means that they cannot take phenyalanine and convert it into tyrosine so remember tyrosine is necessary for epinephrine dopamine melanins um tyrosine is an important precursor to a lot of our hormones so here we have a child um with untreated PKU H so again he can't break down phenyalanine into tyrosine so the phol alanine is going to accumulate in his blood and this causes um abnormal brain development development and with if it's untreated can lead to mental retardation um so one of the symptoms for PKU is that you have 30 to 50 times higher than normal phenol alanine in your blood uh so we've got our phenol alanine here in our patient with PKU we cannot convert this into tyrosine um so if we have too much phenol alanine phenol alanine can be converted into phenol pyruvate um phy um acetate and phy lactate so these three are linked to the neurological deficiency so you have higher amounts of them than normal so it doesn't mean that they're bad in low amounts they're probably very useful for other purposes but when you have too much of them which will happen if you have too much phol alanine then you'll get these neurological deficiencies all right so then these people have PKU then need to avoid um getting phenyalanine in their diet uh so that means that they need to avoid artificial sweeteners like aspartame so aspartame has an aspart and a phol alanine linked together and so when that breaks down you get excess phol alanine so they have to avoid um molecules with neutri uh so this is actually an autosomal recessive gene so for instance if you have two parents that are PKU carriers so this little p indicates that it is recessive so neither of them have symptoms of PKU so um they've got a 25% chance then of creating a normal child that does is not a carrier for PKU they've got a 50% chance of a child who is a carrier but doesn't have a Sy any symptoms of PKU and then a 25% chance of having a child um who you can see has only the recessive genes and then would not just be a carrier of PKU but would be affected um with PK and so another thing is there um if we go back one of the ways we know we need to limit phenol alanine in the diet but we also need to make sure we're getting sufficient tyrosine in our diet so this would be a condition where what we would say is tyrosine is conditionally essential so tyrosine typically is not essential because we should be getting enough phol alanine but because they cannot take phenoline and convert it into tyrosine that means we need to get tyrosine in the diet so they need to make sure that they get low levels of phenyalanine from the diet and high levels higher levels of tyrosine all right so type one albinism is also in this pathway so we've got this enzyme here phenol alanine to tyrosine so um if we have a deficiency here that's where we have PKU but the next enzyme where we go from tyrosine to dopaquinone so remember from our last video dopaquinone was the molecule that made all of our pigments our our melanins so if we do not have this enzyme then that's how we get albinism uh so we cannot make black pig pigments red pigments yellow pigments um Brown pigments and so you can see that they are albinos so people with PKU are not albinos because they can they obtain sufficient amounts of tyrosine in their diets so that tyrosine can go on to make melanin um so but they will have lighter hair and lighter skin at Birth typically because of low levels of tyy so one of the things you should ask yourself is why is PKU treatable but albinism is not even though they are both the effect of genetic mutations and enzymes in our tyrosine metabolism all right the next thing is um a condition called congenital porer so remember that he biosynthesis is one of the important things that we do with the nitrogen that we get from our amino acids so we've got a whole series of reactions to make a a heem so you can see we've got all of these steps so these are the intermediates each of these arrows indicates a step or an enzyme that's necessary and then each of these X's indicates if you don't have that enzyme or if you have a mutation in that enzyme what type of pereria you'll have so you can see dose pereria acute intermittent pereria congenital arthropodic pereria lots of different poras right so again this is going to be um this is actually not going to be a recessive gene this is going to be a a dominant mutation okay so so here we have an affected father so you can see he's got the dominant gene which is the one that carries the pereria and then he has a normal Gene and then the mother has two normal ones so they will have a 50/50 chance of having a normal child and a 5050 chance of having an affected child because it only needs the one gene from the father in order to have pereria all right so there's actually a lot of um belief about people in history having pereria uh so it's thought that King George III of England um would have had pereria based on some of the descriptions of his health that were written at the time of the American Revolution uh so and interestingly enough so this is Vincent Van go and his brother Theo both of them were also thought to have pereria based on some of their descriptions okay so these congenital por feras affect your biosynthesis and one of the rare forms is this congenital orotic pereria so if we go back uh that's this one right here so this enzyme going from this porogen to this porogen we don't have this enzyme so this can cause some really interesting um clinical uh effects so they're going to be characterized by red urine this reddish brown fluorescent teeth so you can see the teeth here they're going to have a sensitivity to sunlight they're going to be very sick or anemic um and so when they go into the sun you can see that it can cause um sores on them and so they're very sensitive to sunlight there's also some theories about how um garlic can help increase your heem production which also is going to increase the amount of symptoms that you see from this congenital pereria so one of the early treatments for congenital pereria was um or is a blood transfusion in order to get Keem and so these people who had um this congenital pereria then would sometimes drink blood because they thought that this would be a way in order to get the heem in their body without having to have a blood transfusion so one of the the more famous people believe to have this congenital arthrotic pereria was Vlad the Impaler so Vlad the Impaler was actually a Romanian and he lived in Transylvania so here is his castle in Transylvania so um he is is Transylvania is a real place so Vlad the Impaler was from the house of dracule uh so he was often called Dracula um and so so this is Dracula from Transylvania and he was believed to have this congenital pereria he had a very high sensitivity to Sun um he was also known for mass murders so he was part of the Crusades to keep Muslims out of um Romania and so he killed thousands and thousands of people so he hence his nickname Vlad the Impaler um and so it's believed that this is where the the myth of vampires came from was from Vlad the Impaler or Dracula who lived in Transylvania who had sensitivity to sunlight and needed to eat blood

okay we&#39;re going to look at the second part of amino acid metabolism so we&#39;ll look at digestion protein turnover our Ura cycle amino acid catabolism and some of our errors in amino acid metabolism all right so all for all of protein synthesis all essential amino acids must be available to the cell so that means before we can even start making a protein we have to have all 20 of our amino acids so if we have a limiting amino acid so we do not have a lot of it we&#39;re going to slow down protein synthesis or even halt it depending on how limiting it is and then if we get inadequate energy consumption so we&#39;re not let&#39;s say we&#39;re not getting enough um glucose or our main energy source or lipids in our diet then we&#39;re also going to limit protein synthesis so we if we have a a too little amount of an amino acid that we need we&#39;re going to slow it down if it&#39;s very low levels of that amino acid we&#39;re going to stop synthesis and if we don&#39;t have enough energy to make anything then we&#39;re going to um limit our protein synthesis as well and this makes sense because if you&#39;re not getting enough energy in your diet then you don&#39;t want to be making new proteins all right so we&#39;ve got two different types of proteins one is called an incomplete protein and one is a complete protein so an incomplete protein just means that it had doesn&#39;t have all of the essential amino acids so not that it doesn&#39;t have all 20 amino acids just it doesn&#39;t have all of the essential amino acids and then a complete prot protein is what we call a high quality protein and that will have sufficient amounts of all of our nine essential amino acids so any of our animal uh proteins will have will be complete proteins and also soy proteins other sources of complete proteins if you are a vegetarian would include a quinoa that would be a complete protein or chia seed would also be a complete protein all right so um in order to get our proper amount of protein in the diet we can do two different things we can have mutual supp mentation or we could have complim um complimentary proteins uh so this Mutual supplementation would be to combine two or more incomplete protein sources to make a complete protein uh so we can do this um when we combine two or more foods to make all nine of our essential amino acids so mutual supplementation would be combining to incomplete protein sources and then the two protein sources that would um be mutual supplementations of each other are called complimentary proteins so here&#39;s some examples here so for instance if we&#39;re looking at legumes legumes do not have enough methionine or cysteine in them however grains nuts and seeds are high in methionine and cysteine so you could do a complimentary food combination with a legume and a grain Nutter seed so for instance rice and lentils red beans and rice rice and blackeyed peas um hummus so hummus will have garbanzo beans and sesame seeds in them so these would be where we have complimentary food combinations that will get us all of the our limiting amino acids so you can see grains are limited in lysine but legumes are high in lysine so peanut butter and bread barley and lentil soup corn tortilla and beans would be examples of a complimentary food combination so many of our vegetables are going to be limited in lysine methionine and seene so our legumes again are um going to have lysine in them and then our grains nuts and seeds will have methionine and cysteine so to U and broccoli with almonds spinach salad with pine nuts and K kidney beans all of these will be examples of how we can make these complimentary food combinations to get all of our essential amino acids all right so let&#39;s look a little bit at our protein digestion so this is going to make uh happen mainly in our stomach and so we&#39;ll have proteases in our stomach that will cleave our peptide bonds to give us take all of those proteins and give us amino acids and small oligopeptides so you can see here um we have our stomach and so we&#39;ve got pepsin pepsinogen these are going to be enzymes that are going to be breaking apart our our peptide bonds and then we go to our uh small intestine here uh I guess technically we go through our large intestine and then our small intestine but in our small intestine then we&#39;re going to have other um bacteria that can digest some of the other proteins for us as well so then these U amino acids will get absorbed into our bloodstream right so our dadum will secrete these interop peptidase so this would be a protease and that is going to be released from our pancreas to help us break down some of our amino acids and uh so it&#39;ll break down different types so uh we can take TR cinogen and take that to Tron using interop peptidase um and then Tron is an enzyme so this is a pro-enzyme we&#39;re converting it into Tron uh Tron can then uh activate kimot tripsin it will also activate elastase and carboxypeptidase actually for fun information carboxypeptidase elastase um and choton are all also Metallo enzymes so you&#39;re using metals to break up these peptide bonds uh so you can see elastase um will&#39;ll take a polypeptide and break it up into polypeptide fragments um sorry so we elastase choton and carboxy peptidase they all do the same thing which is break apart different polypeptides but they do this at different amino acids so we used this in chapter 6 when we took a sequence um a protein sequence and we cleaved it with different um peptidases in order to see what amino acids that we had all right so for n what we&#39;re aiming for is to get what we call nitrogen balance and that means that the nitrogen that we consume in our food is equal to the N nitrogen that we excrete in our urine uh so our waste product for our nitrogen is a molecule called Ura and that&#39;s what makes your PE stink so uh a typical normal healthy adult will need about 400 grams of protein per day to maintain nitrogen balance and obviously that depends on your size metabolism Etc and so go ahead and think what what points in your life would you want to have a positive nitrogen balance where you would want the amount of nitrogen that you consume to be greater than the nitrogen that you excrete uh so some examples of a positive nitrogen balance would be if you are pregnant so you&#39;re going to be creating um a new person so you need to make sure that you have more nitrogen going out than you&#39;re getting rid of because you&#39;re using that nitrogen uh points in your life when you might have a negative nitrogen balance would be um periods of fasting or starvation possibly even sickness all right so there are of course examples of people with extreme protein energy malnutrition so two of the most um uh visible are marasmus and Kashi oror so marasmus you&#39;re going to have in quate intake of protein and all other nutrients uh so this is both a protein malnutrition and energy malnutrition so not enough lipids and N enough carbohydrates uh you get a wasting and the weakening of the muscles and that includes the heart because you&#39;re using all of the muscles in order to uh in order to to sustain life and eventually you&#39;ll die from Death from dehydration heart failure or infection uh because we&#39;re not able to make any of our antibodies that we need our heart start starts to weaken as we&#39;re we&#39;re using it for energy uh in quashi or cor um this is a gan word that means the stick the sickness that the baby gets when the new baby comes uh so in this case they&#39;re getting sufficient calories but their calories are from only carbohydrate sources so they&#39;re getting insufficient protein in their diet but still sufficient energy in their diet um but we still will see muscle wasting and we&#39;ll also see EMA so here is some example of of what this looks like so again marasmus it&#39;s going to be characterized by stunted growth uh depressed metabolism uh you want to slow down the energy consumption as much as possible uh to try to maintain life as long as possible uh you&#39;re going to have a very low body temperature because you&#39;re not going to be um going creating a lot of energy in general um you&#39;ll start to deteriorate your intestinal lining you&#39;ll have stuned brain development and anemia so these are the the the children where you can see their ribs um and it&#39;s they General wasting away um they do not grow very big and they have very stunted brain development um so you&#39;ll see that they still have normal hair and they have what is described as an old man&#39;s face uh and then one of the key ways that we can differentiate between marasmus and um quasi oror is that in marasmus we&#39;ll see no edema in quasi oror this is where we see these children with these distended bellies um so we&#39;ll get some retention of body fat remember that um they&#39;re still getting some sufficient calories in their diet um but because they&#39;re not getting enough protein there will be [ __ ] growth [ __ ] development um so slowed growth and development and then because of the fact that they have a lack of protein in their diets they&#39;ll also suffer from edema so edema is where you get the water and so you can see examples of Edema here and these bellies as well um this is where you don&#39;t have the proteins to maintain your fluid balance so your cells can&#39;t hold in water um so your cells can&#39;t hold in water so the water will just pull in places where it shouldn&#39;t be you&#39;ll see a loss of appetite you&#39;ll get these um hair changes so dry brittle brittle hair uh lots of sores and in general sadness and apathy uh for marasmus these these um people don&#39;t apparently seem to even understand what&#39;s happening to them to the level where they don&#39;t have this um misery or sadness or apathy about them that the kashor core people do okay so let&#39;s then talk about how our amino acids can be turned into energy so how do we break down our proteins to turn it into energy uh so we&#39;re going to take our cellular proteins our dietary proteins and we&#39;re going to break them down into amino acids so that&#39;s the first thing that we have to do is break everything down into amino acids we&#39;re going to take this ammonia um from the amino acid and we can turn this into other amino acids we saw that in the last video we can turn it into nucleotides other biological Ames um or we can convert it to carbo phosphate which we see which will then go through our Ura cycle and create Ura then our carbon skeleton that can be taken and depending on the amino acid that we are using it can be taken to the citric acid cycle it could be made into pyate or oxel acetate or it could be made into acetal koay so we can take these amino acids and get directly ATP we could get glucose or could get fatty acids and Ketone bodies so uh what does the Ura cycle accomplish for the organism so it&#39;s going to provide an effective me uh mechanism to remove excess nitrogen from the body I the Ura will be synthesized in the liver and then exported to the kidneys where it will then go to your bladder so we&#39;re going to take the ammonium ion we&#39;re going to take some bicarbonate aspartate and 3 ATP and make Ura Fumarate and then 2 ADP so our key enzymes carban oil phosphate synthetase 1 so that&#39;s going to be our committed step um so we&#39;re going to take our amino acids and we&#39;re going to be doing aminotransferase reactions our goal is to get all of our amino acids into glutamate uh so we&#39;ll take our glutamine that we have and we&#39;ll take that ammonia and make ammonium ion from that and that ammonium ion will go to make carbano phosphate which will go into our Ura cycle and then our glutamates will use this aspartate aminotransferase so we can see we&#39;ve got oxaloacetate here to um transfer this ammonium group to oxaloacetate to make aspartate then aspartate and carbano phosphate we&#39;ll be going into our Ura cycle so here is our Ura cycle we&#39;ve got our carb oil phosphate so that&#39;s that nitrogen um and here this blue box is representing orane and um so this this molecule here will have ornithine and carban oil phosphate on it then we&#39;ll add in aspartate so here is aspartate here and so this is the nitrogen here from the aspartate amino acid here is our Alpha carbon our carboxy group our side chain from aspartate um through a series of reactions then we&#39;ll release Fumarate uh so we know Fumarate can go into our citric acid cycle and then now we&#39;ve got here this Arginine so we&#39;ve got ornithine with uh carbon with two nitrogens on it and then we will uh release this to make Ura and then we&#39;ll have ornithine remaining and then we can continue through this cycle so you can see we put in a carban oil phosphate with a nitrogen we put in um an aspartate with a nitrogen and we get out Fumarate with no nitrogens and Ura with two nitrogens so here&#39;s just another view of that exact same process but this time showing you the structure of ornithine so here&#39;s ornithine here will get transported into the mitochondrial Matrix will combine with carbano phosphate um and then through a series of reactions then uh that we&#39;re going to use ATP we&#39;ll get out this um we&#39;ll put in our aspartate molecule here and now we have this new molecule that has aspartate which is here that nitrogen um from carban oil phosphate there and then this is our ornithine group we release the Fumarate which is from our aspartate and then now these two nitrogens that are attached to our orine um will get hydrolized with water to make Ura and release that ornithine so this is just the structural view of this slide here showing you what this blue box looks like all right so our Ura cycle um we&#39;re including um this pyrro phosphate reaction we are going to use three high energy phosphate bonds so this is essentially three ATP equivalents for every Ura that&#39;s synthesized so I&#39;ll point that out to you here so first um this carbano phosphate has a high energy Bond we&#39;re releasing a phosphate this bond is a high energy Bond so that would be one ATP equivalent our second is here when we actually use ATP and then our third we&#39;re going to take a sparate and take it into a&amp; um and so that will also uh you can see we&#39;re using this um&amp; intermediate that will also be a high energy bond that we&#39;re breaking so we&#39;re using the equivalent of 3 ATP to make one Ura right so that Fumarate that we get um from our citric or sorry from our Ura cycle so here&#39;s the Fumarate that is made from our Ura cycle is then converted into malate malate is transported into the Matrix of the cell and then malate is turned into oxaloacetate and that oxaloacetate can be used for citric acid cycle or we could take that oxaloacetate if we needed to and convert it into aspartate and then use that aspartate to further fuel the Ura cycle all right so we also could have um enzyme deficiencies in our Ura cycle um so Aros oxinate is soluble and can be excreted in the urine uh so that is this molecule here uh so if for some reason we are not able to complete our Ura cycle we just don&#39;t release our um in our urine Ura we instead release this arinos seexan that&#39;s excreted in the urine one of the ways that you can tell that you have um someone who has this deficiency is they&#39;ll have a high amount of arginine in their diet or sorry they&#39;ll need to ingest high amounts of arginine in order to make this Ura cycle go since it&#39;s missing the capability of turning turning this AR arginosuccinate into Arginine so that would be how to fix it if you were someone who had this deficiency all right so our degradation of our amino acids leads to two different types of amino um precursors uh one we call our glucogenic and the other one we call our ketogenic uh so our I&#39;ll go to the next slide because we&#39;ve got actually some pictures here so all of the ones that are blue are ones that we consider glucogenic um because we&#39;re taking these amino acids and turning them into something that could be achieved using uh glycolysis so pyruvate and citric acid cycle intermediates uh the ones that are ketogenic are going to be the ones that are turned into molecules um essentially aceto COA and aceto acetate that are mainly used in our ketogenesis right so now let&#39;s look at some errors in our amino acid metabolism H so one of the ones uh that&#39;s I wouldn&#39;t say common but is is very common in textbooks uh is this pheno keto um ketona so PKU and an individual that has this does not have the enzyme or has a deficiency or a um a mutation in the enzyme for pheny alanine hydroxy such that it doesn&#39;t work and so that means that they cannot take phenyalanine and convert it into tyrosine so remember tyrosine is necessary for epinephrine dopamine melanins um tyrosine is an important precursor to a lot of our hormones so here we have a child um with untreated PKU H so again he can&#39;t break down phenyalanine into tyrosine so the phol alanine is going to accumulate in his blood and this causes um abnormal brain development development and with if it&#39;s untreated can lead to mental retardation um so one of the symptoms for PKU is that you have 30 to 50 times higher than normal phenol alanine in your blood uh so we&#39;ve got our phenol alanine here in our patient with PKU we cannot convert this into tyrosine um so if we have too much phenol alanine phenol alanine can be converted into phenol pyruvate um phy um acetate and phy lactate so these three are linked to the neurological deficiency so you have higher amounts of them than normal so it doesn&#39;t mean that they&#39;re bad in low amounts they&#39;re probably very useful for other purposes but when you have too much of them which will happen if you have too much phol alanine then you&#39;ll get these neurological deficiencies all right so then these people have PKU then need to avoid um getting phenyalanine in their diet uh so that means that they need to avoid artificial sweeteners like aspartame so aspartame has an aspart and a phol alanine linked together and so when that breaks down you get excess phol alanine so they have to avoid um molecules with neutri uh so this is actually an autosomal recessive gene so for instance if you have two parents that are PKU carriers so this little p indicates that it is recessive so neither of them have symptoms of PKU so um they&#39;ve got a 25% chance then of creating a normal child that does is not a carrier for PKU they&#39;ve got a 50% chance of a child who is a carrier but doesn&#39;t have a Sy any symptoms of PKU and then a 25% chance of having a child um who you can see has only the recessive genes and then would not just be a carrier of PKU but would be affected um with PK and so another thing is there um if we go back one of the ways we know we need to limit phenol alanine in the diet but we also need to make sure we&#39;re getting sufficient tyrosine in our diet so this would be a condition where what we would say is tyrosine is conditionally essential so tyrosine typically is not essential because we should be getting enough phol alanine but because they cannot take phenoline and convert it into tyrosine that means we need to get tyrosine in the diet so they need to make sure that they get low levels of phenyalanine from the diet and high levels higher levels of tyrosine all right so type one albinism is also in this pathway so we&#39;ve got this enzyme here phenol alanine to tyrosine so um if we have a deficiency here that&#39;s where we have PKU but the next enzyme where we go from tyrosine to dopaquinone so remember from our last video dopaquinone was the molecule that made all of our pigments our our melanins so if we do not have this enzyme then that&#39;s how we get albinism uh so we cannot make black pig pigments red pigments yellow pigments um Brown pigments and so you can see that they are albinos so people with PKU are not albinos because they can they obtain sufficient amounts of tyrosine in their diets so that tyrosine can go on to make melanin um so but they will have lighter hair and lighter skin at Birth typically because of low levels of tyy so one of the things you should ask yourself is why is PKU treatable but albinism is not even though they are both the effect of genetic mutations and enzymes in our tyrosine metabolism all right the next thing is um a condition called congenital porer so remember that he biosynthesis is one of the important things that we do with the nitrogen that we get from our amino acids so we&#39;ve got a whole series of reactions to make a a heem so you can see we&#39;ve got all of these steps so these are the intermediates each of these arrows indicates a step or an enzyme that&#39;s necessary and then each of these X&#39;s indicates if you don&#39;t have that enzyme or if you have a mutation in that enzyme what type of pereria you&#39;ll have so you can see dose pereria acute intermittent pereria congenital arthropodic pereria lots of different poras right so again this is going to be um this is actually not going to be a recessive gene this is going to be a a dominant mutation okay so so here we have an affected father so you can see he&#39;s got the dominant gene which is the one that carries the pereria and then he has a normal Gene and then the mother has two normal ones so they will have a 50/50 chance of having a normal child and a 5050 chance of having an affected child because it only needs the one gene from the father in order to have pereria all right so there&#39;s actually a lot of um belief about people in history having pereria uh so it&#39;s thought that King George III of England um would have had pereria based on some of the descriptions of his health that were written at the time of the American Revolution uh so and interestingly enough so this is Vincent Van go and his brother Theo both of them were also thought to have pereria based on some of their descriptions okay so these congenital por feras affect your biosynthesis and one of the rare forms is this congenital orotic pereria so if we go back uh that&#39;s this one right here so this enzyme going from this porogen to this porogen we don&#39;t have this enzyme so this can cause some really interesting um clinical uh effects so they&#39;re going to be characterized by red urine this reddish brown fluorescent teeth so you can see the teeth here they&#39;re going to have a sensitivity to sunlight they&#39;re going to be very sick or anemic um and so when they go into the sun you can see that it can cause um sores on them and so they&#39;re very sensitive to sunlight there&#39;s also some theories about how um garlic can help increase your heem production which also is going to increase the amount of symptoms that you see from this congenital pereria so one of the early treatments for congenital pereria was um or is a blood transfusion in order to get Keem and so these people who had um this congenital pereria then would sometimes drink blood because they thought that this would be a way in order to get the heem in their body without having to have a blood transfusion so one of the the more famous people believe to have this congenital arthrotic pereria was Vlad the Impaler so Vlad the Impaler was actually a Romanian and he lived in Transylvania so here is his castle in Transylvania so um he is is Transylvania is a real place so Vlad the Impaler was from the house of dracule uh so he was often called Dracula um and so so this is Dracula from Transylvania and he was believed to have this congenital pereria he had a very high sensitivity to Sun um he was also known for mass murders so he was part of the Crusades to keep Muslims out of um Romania and so he killed thousands and thousands of people so he hence his nickname Vlad the Impaler um and so it&#39;s believed that this is where the the myth of vampires came from was from Vlad the Impaler or Dracula who lived in Transylvania who had sensitivity to sunlight and needed to eat blood

Transcript for:Amino Acid Metabolism Part II

Transcript for:
Amino Acid Metabolism Part II