I engineers in this video we're going to talk about the urea cycle ok so specifically if you guys remember where we 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 keto blue turi then alpha keto butyrate 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 let's actually make these different colors let's make alanine green that way we don't confuse it let's say here is alanine Ali 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 in the name of that enzyme was alanine amino transferase or alt 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 actually getting transported during 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 remembered 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 in a dp+ and converting it into an a/d pH 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 yeah getting 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 ammonium which is extremely extremely toxic and we'll talk about why it's toxic then the glutamate is also going to have a hydration steps 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 glue to rate and you guys remember that the alpha keto glued array could go and react with a lean II can rack with aspartate and continue those transamination processes what was the enzyme that was driving this step this enzyme if you guys remember that was driving this step was called glutamate D hydrogenation fun ok so this is the glutamate dehydrogenase enzyme and he is stimulating to 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 one of those two pathways specifically could use in free radical reactions 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 and certain points it can actually gain a proton so say a games a proton if it gains this proton it actually turns into in age for positive you know this is called ammonium when would you be generating a lot of ammonia towards toxic if there's maybe some type of condition where there's excessive protein breakdown or degradation if there's excessive protein breakdown and degradation you're going to make a lot of ammonia you know certain types of bodybuilders who are taking in excessively large amounts of protein so much 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 cantab alized consistently what is it going to do is going to generate tons and tons of ammonia that ammonia is super toxic to these actual bodybuilders and we'll explain why so what is this ammonia do it can actually convert into ammonium it's ammonium it can actually get pushed out here into the bloodstream and then you know it can happen okay in our brain we have 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 astrocytes so what is this guy right here called this is a astrocyte 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 astrocytes is that they have a special enzyme that not many tissue cells have this enzyme is called glutamine synthetase or synthase but I'm gonna put cyntha taste what do I mean this glutamine synthetase is a special enzyme and what does glutamine synthetase does is is it converts a molecule called gluta mate into gluta mean so again what does that molecule that it can make as a result it can make a molecule called gluta mean now in order for glutamate to be converted into glutamine what do you need to add you know all the differences between glutamate and glutamine is an amine group so you know what can happen this ammonium that we generated from this 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 it into this process of converting glutamate with the ammonium into glutamine why is this dangerous because you know gluten automatically 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 we're into the brain what do you call that whenever you pull holes 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 extreme I call it Ernie ation of the brain or it can even lead to comatose it could lead to comatose you can actually go into a 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 bring glutamate excessive amounts of ammonia lead to excessive amounts of glutamine if there's success excessive amounts of glutamine it's going to suck water into the brain and lead to cerebral edema which you need to high intracranial pressure or maybe in comatose and if there's high intracranial 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 this excessive amounts of glycine so we can have a lot of glycine or we can have a lot of glutamine because of the success of 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 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 you into mitochondria once it's in the mitochondria it's going to combine with the special couple special molecules so see here I redraw here's my ammonium and it's more 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 HSH do three negative and then I have to run this reaction in the presence of adenosine triphosphate ATP so now I need ATP for this reaction okay in order for this to happen order for me to take the bicarbonate the NH four 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 carbamoyl phosphate so what is this molecule called it's called carbamoyl carbamoyl phosphate and the enzyme that's working in the step is trying to synthesize the carbamoyl phosphate so what enzyme do you think this is we're going to abbreviate it here it's called carbamoyl phosphate synthetase type 1 so again what is this enzyme here called this enzyme is specifically called carbamoyl phosphate synthetase type one now what this enzyme is going to do is it's going to convert to ATP the ammonium and the bicarbonate ions into carbamoyl phosphate then what's going to happen you know there's molecule that we actually have a lot of inside of this area it's not actually a type of amino acid that we actually we actually make this amino acid about either so you know there's different types of amino acids essential amino acids and nonsense non-essential amino acids so with essential amino acid we actually have to take those actual amino acids into the diet whereas non-essential amino acids can actually make those in the body we don't have to get 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 carbonyl phosphate so look what happens here as a result I'm going to take the ornithine and I'm going to take the carbon little phosphate and I'm going to combine them okay so I'm taking these two guys who who am I taking it I'm taking the ornithine and I'm taking the carbon one 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 citrulline new molecule is called citrulline then after I do this I need an enzyme to catalyze this step this enzyme is extremely extremely important this enzyme is called ornithine transcarbamylase trans carbon oil ace enzyme this ornithine transcarbamylase enzyme is going to catalyze this step so again what are you doing he's taking the ornithine fusing with the carbonyl phosphate and turning it into citrulline now this citrulline he's going to combine with a special molecule you know what that molecule is called that molecule is called aspartate but question is just see if you guys are linking this all together where does that aspartate coming from you remember there was a shuttle that I used to take the Mallee and push the malate in and then I used that same shuttle to push another molecule out pulls that molecule aspartate so now I can push out this molecule called aspartate or the aspartate I guess would be nicer to say right and then the aspartate is going to do what it's going to fuse with this citrulline so now this citrulline actually done with a pink arrow make it look pretty this citrulline 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 Arjun o Arjun o succinate Arjun alas oxen eight is being formed from the actual conversion of or the reaction of citrulline an aspartate now what enzyme is catalyzing this reaction this enzyme is called our genome socks innate synthase or synthetase right and what this enzyme is doing is is it taking these two molecules and reacting them together and stimulating this step and so now citrulline and aspartate will then be reacted on my arjun of succinate I'm sorry Arjun of succinate synthetase to convert it into Arjun o socks and then Arjun o succinate is going to have another enzyme so now look what's going to happen as a result here the arjun of socks innate is going to go into this next step and in this step out of the arjun of succinate 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 few married I'm going to pop off a few marry when I pop off the few marry it then converts Arjun o succinate into another molecule referred to as arginine arja mean now when this Arjun o suction is converting to Arjun there's a specific enzyme that is involved in this process this enzyme is called Arjun o succinate so the enzyme catalyzing this reaction here is called Arjun L succinate enzyme so this Arjun o succinate enzyme is actually ripping the few married out of arjun of socks and converting them into arginine now we get to the most important part you know with still hanging into that arginine this this actual ammonia is kind of been hidden in all of these structures but it's undergoing specific types of modifications there's a specific component of the Arjun I'm going to rip out in this next step so in this next step I'm going to convert the arginine 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 Arjun ace Arjun ace and what Arjun ace is doing in this is our jenay's is acting on the arginine and yanking out a special structure what is that special molecule yank from this this is called urea so then we yank out of this the urea where can that urea go the urea can then eventually go into the blood and then get sent to the kidneys and then if it's taken into the kidneys where what will happen in the kidneys you're going to urinate it out because this is a nitrogenous waste product so this is actually getting sent into the blood taking to the kidneys and urinated out of the body you know you read also has other product process that we'll talk about in renal physiology with helping or cycling for the osmotic gradients okay now when we push this urea out then it can get urinated out and help to decrease the actual ammonia levels all right so now now that we put this urea into the bloodstream so now that you Riyaz in the bloodstream like I said it can go to the kidney can get urinated out so we can try to get rid of the ammonia inside of a less toxic form so ammonia is extremely toxic and so it's always urea but it's actually significantly less toxic as compared to ammonia now I just our get rid of getting rid of the ammonia so you can imagine any type of deficiency or mutation in any of these enzymes particularly ornithine transcarbamylase or arjuna succinate synthetase or even our genus oxidase 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 one of these urea cycle enzymes and your ammonia level or your Moneo level is significantly high and you have this cerebral edema due the accumulation of a lot of glutamine and a lot of glycine so also a lot of glycine how do they treat this and they give these people what's called benzoate or they can also give another molecule called phenol butyrate 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 benzoate is helping to be able to pick up some of these molecules and some of the phenyl butyrate so zowie and phenol be uh the phenol butyrate 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 the spindle butyrate when it pulls up this glutamine in is glycine where can it go it can then go to the kidneys and in the kidneys it will excrete these molecules in the urine okay so our body has a very interesting way of dealing with this right this ammonia this toxic molecule blood in certain conditions in which maybe there's a defect in the actual urea cycle enzymes there is a significant increase in these actual ammonia levels and you could develop a lot of glutamine accumulation a lot of glycine accumulation you can give these people benzoate or phenol butyrate 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 your decrease in that toxicity in the body iron engineers I hope all of this made sense guys hope you guys all enjoyed it if you did hit that like button subscribe we have a comment down the comment section all right ninja nerds until next time