I engineers in this video we're going to talk about the Ura cycle okay so specifically if you guys remember where we left left off last we talked about transamination and oxidative deamination let's just go really really fast through that so if you remember inside of the muscle we have a specific amino acid that we wanted to talk about and that was alanine right and if you guys remember alanine was combining with a specific keto acid which was called Alpha ketoglutarate then Alpha ketoglutarate and alanine were reacting and what happened you formed two different things one is you formed we're going to put over here alanine will form specifically oh let's actually make these different colors let's make alanine green that way we don't confuse it so let's say here's alanine alany will get converted into pyruvate but then Alpha ketoglutarate will get converted into a specific amino acid which is called glutamate now this again was driven by a specific enzyme and the name of that enzyme was alanine Amino transferase or Al LT for short and this is again if you guys remember this is also a reversible pathway okay then we said that the glutamate was actually coming into the blood and going to the liver so let's actually bring this glutamate over here it's actually getting transported through the blood and then what into the liver then what did we say then we said once we had this glutamate specifically over here inside of this actual liver cell you guys remember that there was a special enzyme and that special enzyme in this process was doing a couple things one thing that it was doing is it was taking n a DP positive and converting it into n a dph so what is happening this is undergoing he's undergoing reduction but he's oxidizing the glutamate another thing that you'll remember is that we're specifically yanking a specific component out of the glutamate what is that specific component that we're yanking out of the glutamate we're pulling out ammonia all right so this is our ammonia which is extremely extremely toxic and we'll talk about why it's toxic then the glut aate is also going to have a hydration step so you know you're going to add water into this component right because you know this is a two-step reaction so water is added into this step in the second step and then you're going to generate Alpha keto glutarate and you guys remember that that Alpha ketoglutarate could go and react with Alan could react with a sparate and continue those transamination processes what was the enzyme that was driving this this step this enzyme if you guys remember that was driving this step was called glutamate dehydrogenase enzyme okay so this is the glutamate dehydrogenase enzyme and he is stimulating this Pathway to convert glutamate into Alpha ketoglutarate adding in water generating an nadph which is a good reducing agent which could be used in two pathways of those two Pathways specifically could use in free radical reactions uh with applications to the glutathione and then another one is fatty acid synthesis okay then we push out the ammonia now let's talk about briefly why ammonia is toxic you know another thing can happen to the ammonia in certain points it can actually gain a proton so let's say it gains a proton if it gains this proton it actually turns into nh4 positive you know this is called ammonium when would you be generating a lot of ammonium to where it's toxic if there's maybe some type of condition where there is excessive protein breakdown or degradation if there's excessive protein breakdown and degradation you're going to make a lot of amonia you know certain types of bodybuilders who are taking in excessively large amounts of protein so much prot protein to their body can't actually incorporate into the tissues anymore and it starts getting broken down as those proteins are getting broken down and metabolized consistently what is it going to do it's going to generate tons and tons of ammonia that ammonia is super toxic to these actual bodybuilders and we'll explain why so what does this ammonia do it can actually get converted into ammonium you know this ammonium it can actually get pushed out here into the bloodstream and then you know what can happen Okay in our brain we have spefic specific types of cells you know what these cells are called that are actually found inside of our brain and they're controlling what's leaving the blood and entering into like the neural tissues out here this guy right here look at this guy this is called a astroy so what is this guy right here called This is a astroy astrocytes are very very special type of cells we'll talk about these in neuro but what's kind of really really cool about these Astros sites is that they have a special enzyme that not many tissue cells have this enzyme is called glutamine synthetase or synthes but I'm going to put synthase what do I mean this glutamine synthetase is a special enzyme and what this glutamine synthetase does is is it converts a molecule called gluta mate into glutamine so again what is that molecule that it can make as a result it can make make a molecule called gluta me now in order for glutamate to be converted into glutamine what do you need to add you know all the differences between glutamine and glutamine is an amine group so you know what can happen this ammonium that we generated from this uh you know amino acid catabolism process let's say I take this ammonium here and I have this ammonium and I incorporate it into here so now I'm going to have this ammonium here and I'm going to incorporate into this process of converting glutamate with the ammonium into glutamine why is this dangerous because you know glutamine is osmotically active you know what that means so let's say that I have a lot of water flowing through this area through cerebral blood vessels right so here's a lot of water and as there's a buildup of glutamine due to excessive amounts of ammonia in the form of ammonium right if there's excessive amounts of this ammonium I'm going to make excessive amounts of glutamine what is that going to do that's going to suck water where into the brain what do you call that whenever you pull pull significant amounts of water into the brain they call this cerebral edema brain swelling why is that dangerous because you know brain swelling can actually raise intracranial pressure so your intracranial pressure could increase which can cause EXT might cause herniation of the brain or it can even lead to komos it could lead to comos you could actually go into coma because of excessive amounts of this ammonia so this ammonia is causing significant cerebral edema by pulling water in how by reacting with the glutamine synthetase and bringing glutamate excessive amounts of ammonia lead to excessive amounts of glutamine if there's excessive amounts of glutamine it's going to suck water into the brain and lead to cerebrala which can lead to high OC cranial pressure or maybe even comos and if there's High inoc cranial pressure it can lead to the brain herniation which is extremely dangerous okay not only can it do that the ammonium can also combine with another molecule to form what's called glycine so you can also we're not going to talk about the mechanism but you can have this ammonium being incorporated into a molecule and leading into the formation of excessive amounts of glycine so we can have a lot of glycine or we can have a lot of glutamine because of this excessive amounts of ammonium and again these two molecules can pull water into the brain or other different tissue cells and this can be extremely disastrous neurotoxic damage to the neurons so how do we deal with that we'll talk about how we deal with it it gets so excessive but that's why it can become very dangerous how do we deal with that and prevent that from happening okay see this ammonia or we can actually convert into ammonium I'm going to take this ammonium and I'm going to push it into the mitochondria okay I'm going to push it into the mitochondria once it's in the mitochondria it's going to combine with a special couple special molecules so see here I redraw here's my ammonium nh4 positive I'm going to combine this with another two molecules so let's say I combine it with bicarbonate but specifically about two units of bicarbonate so two bicarbonates okay so here's my bicarbonate H hc3 negative and then I have to run this reaction in the presence of adenosine triphosphate ATP so now I need at P for this reaction okay in order for this to happen in order for me to take the bicarbonate the nh4 plus and the ATP and convert all of that into a new molecule I'm going to need a special enzyme for this process this new molecule that I'm going to make is called carbom oil phosphate so what is this molecule called it's called carbom moil carbon Mo phosphate and the enzyme that's working in this step is trying to synthesize the Carbono phosphate so what enzyme do you think this is we're going to abbreviate it here it's called carbom moil phosphate synthetase type one so again what is this enzyme here called this enzyme is specifically called carbom moil phosphate synthetase type one now what this enzyme is going to do is it's going to convert the ATP the ammonium and the bicarbonate ions into Carbono phosphate then what's G to happen you know there's molecule that we actually have a lot of inside of this area it's it's it's not actually a type of amino acid that we actually M we actually make this amino acid in our body there's you know there's different types of amino acids essential amino acids and non non-essential amino acids so with essential amino acids we actually have to take those actual amino acids in through the diet whereas non-essential amino acids we can actually make those in the body we don't have to get it through the diet one of those is actually called ornithine so we have a molecule called ornithine ornithine is going to come in and it's going to combine with the carbon phosphate so look what happens here as a result I'm going to take the ornithine and I'm going to take the Carbono phosphate and I'm going to combine them okay so I'm taking these two guys who who am I taking here I'm taking the ornithine and I'm taking the carbon moil phosphate and I'm combining these two guys and converting them into a new molecule what is this new molecule called this new molecule call is called citrine this new molecule is called citrine then after I do this I need an enzyme to catalyze this step this enzyme is extremely extremely important this enzyme is called ornithine trans carbom moas trans carbo moas enzyme this ornithine trans carbom enzyme is going to catalyze this step so again what is he doing he's taking the ornithine fusing with the carbom phosphate and turning it into citrine now this citrine he's going to combine with a special molecule you know what that molecule is called that molecule is called aspartate but question is to see if you guys are linking this all together where is that aspartate coming from you remember there was a shuttle that I used to take the malate and pushed the malate in and then I used that same shuttle to push another molecule out what was that molecule aspartate so now I can push out this molecule called aspirate or the aspartate I guess it would be nicer to say right and then the aspartate is going to do what it's going to fuse with this citrine so now this citrine let's actually draw with a pink Arrow make it look pretty this citrine is going to combine with the aspartate when these two molecules fuse together they're going to make a new molecule and this molecule is called Argin Argos succinate arinos soate is being formed from the actual conversion of or the reaction of citrine and aspartate now what enzyme is catalyzing this reaction this enzyme is called Argin soyate synthes or synthetase right and what this enzyme is doing is is it's taking these two molecules and reacting them together and stimulating this step and so now citrine and a sparate will then be reacted on by arinos suxin I'm sorry arginate synthetase to convert it into arginate then arinos soate is going to have another enzyme so now look what's going to happen as a result here the Argin oxinate is going to go into this next step and in this step out of the arginosuccinate I'm going to release out another molecule what is that molecule that I'm going to pop out of here I'm going to get rid of fumate I'm going to pop off a fumate when I pop off the fumate it then converts arinos suin into another molecule referred to as Arginine arine now when this arinos oxinate is converted into Argin there's a specific enzyme that is involved in this process this enzyme is called arinos soase so the enzyme catalyzing this reaction here is called Argin suas enzyme so this arinos soase enzyme is actually ripping the fume out of arinos oxinate and converting them into Arginine now we get to the most important part you know was still still hanging into that argine this this actual ammonia has kind of been hidden in all of these structures but it's undergoing specific types of modifications there's a specific component of the Argin that I'm going to rip out in this next step so in this next step I'm going to convert the argine back into ornithine because it's going to be a nice cycle right but in that process I'm going to have another special enzyme this is a very very important enzyme this enzyme is called arginase arginase and what arginase is doing in this step is arginase is acting on the Arginine and yanking out a special structure what is that special molecule yanked from this this is called Ura so then we yank out of this the Ura where can that Ura go the Ura can then eventually go into the blood and then get sent to the kidneys and then if it's taken into the kidneys where will what will happen in the kidneys you're going to urinate it out because this is a nitrogenous waste product so this is actually going to sent into the blood takeen to the kidneys and urinate out of the body but you know Ura also has other Pro process that we'll talk about in renal physiology with helping with recycling for the osmotic gradients okay now when we push this curea out then it can get urinated out and help to decrease the actual ammonia levels all right so now now that we put this Ura into the bloodstream so now this Ura is in the bloodstream like I said it can go to the kidney it can get urinated out so we can try to get rid of the Ammon Amia inside of a less toxic form so ammonia is extremely toxic and so so is Ura but it's it's actually significantly less toxic as compared to ammonia now this is how we're get rid getting rid of the ammonia so you can imagine any type of deficiency or mutation in any of these enzymes particularly ornithine transc carbom AE or arinos soate synthetase or even arinos suat can cause significant or detrimental effects on the body now in conditions in which there is this situation where you might have some type of deficiency or some type of mutation in one of these Ura cycle enzymes and your ammonia level or your ammonium level is significantly high and you have this cerebral edema due to the accumulation of a lot of glutamine and a lot of glycine so also a lot of glycine how do they treat this they give these people what's called benzoate or they can also give another molecule called fenel berate what do these two molecules do that helps to alleviate some of these problems these guys are specifically binding on to the glutamine and the glycine you know specifically the benzoid is helping to be able to pick up some of these molecules and some some is the falate so benzo and fenal uh the phenate are doing what they're yanking what they're yanking this glutamine and they're yanking the glycine out of the actual tissues and as you're pulling out more glutamine more glycine you're getting rid of ammonia out of the blood where is this going to go it's going to go on to These Guys these benzoate and this phenolate when it pulls up this glutamine and this glycine where can it go it can then go to the kidneys and in the kidneys it'll excrete these molecules in the urine okay so our body has a very interesting way of dealing with this right this ammonia this tox molecule but in certain conditions in which maybe there's a defect in the actual Ura cycle enzymes and there's a significant increase in these actual ammonia levels and you can develop a lot of glutamine accumulation a lot of glycine accumulation you can give these people benzoate or phenate and whenever you give them these molecules they can help to actually pull some of the Glycine and pull some of the glutamine from the tissues and from the blood and do what take it to the kidneys to be excreted in the urine if you excrete those those molecules in the urine you've technically gotten rid of some of the ammonia and you're decreasing that toxicity in the body all right ners I hope all of this made sense guys I hope you guys all enjoyed it if you did hit that like button subscribe leave a comment down in the comment section all right Ninja nerds until next time