Metabolism | Ketone Metabolism

iron engineers in this video we're going to talk about ketone metabolism okay so when does the body actually you know you life ketone it's not our usually preferable source of energy it is usually usually utilized whenever we're in certain conditions so let's say that you have low blood glucose levels let's say it's one reason all right so let's say that you have extremely low blood glucose levels another reason this pathway could occur this ketone metabolism could be if you're actually have prolonged starvation so another reason could be prolonged starvation so prolonged starvation another reason this pathway could occur is because of diabetic conditions so in other words you have diabetes mellitus and it's not being well regulated so you're not taking your insulin properly so it could be due to uncontrolled diabetes mellitus specifically though type 1 it's less common in type 2 but it can happen in type 2 and the last thing is it could be due to a some type of diet where you're restricting carbohydrates for example the Atkins diet okay so these could be certain conditions or reasons upon why you're exhibiting this ketone metabolism now why are these things stimuli for that okay if your actual having low blood glucose levels your body is going to have to utilize some form of energy now the brain this is the brains primary source of energy so the brain's primary source of energy is going to be that of glucose but in any condition in which there is extremely low blood glucose levels whether it be due to prolonged starvation uncontrolled diabetes mellitus type 1 or some type of specialized diet where you're avoiding carbohydrates moreover ketogenic diet like the Atkins diet this can cause the brain to have to switch from its primary choice of fuel to a secondary choice of fuel which is that a ketone bodies also the muscles our muscle tissues can also utilize these ketone bodies so our muscles they also prefer to use fatty acids and glucose as their source of energy but whenever there is a situation which the blood glucose levels are extremely low and there's excessive fatty acid oxidation they can utilize ketone bodies so again we know why it's occurring it's occurring because of low blood glucose levels whether that be due to prolonged starvation uncontrolled type 1 diabetes mellitus or the Atkins diet or some type of diet which is restricting carbohydrates now we know that the organs that can utilize that as sources of fuel is going to be the brain and the muscles now the next question is where is this ketogenesis actually occurring it's mainly occurring in the liver so this is mainly occurring in the liver this is where the the genesis of these ketone bodies are being formed but the lysis the breaking down of those ketone bodies to generate energy is occurring within the muscles and the brain ok now let's go over how this process is occurring and why it's occurring and a little bit more detail so you know how inside of our liver cell it's utilizing glucose it can utilize glucose and you guys remember that glucose undergoes oxidation to produce pyruvate and then if you remember pyruvate can get converted into what eventually you can get converted into acetyl co a and then what does the co co a combined with you know if you look away it combines with occitane I'm going to note that it's Oh a a and what happens if you guys remember oxaloacetate in acetyl co a actually do what they fuse together right to form what molecule what is this next molecule that it forms it forms a molecule called citrate and then in the Krebs cycle will continue rays will go from citrate to isocitrate to alpha ketoglutarate to succinylcholine Sox innate if you marry to Mally to oh eh eh okay you know there's another path that can occur if the glucose levels in our body is low we have low blood glucose levels wouldn't that mean that we have very little pyruvate if we have very little pyruvate we have very little acetyl co a and there's going to be less krebs cycle activity and now what that means is is you know your body has to take this to a specific point on the body you know it takes it to the electron transport chain you know the NADH is that you get from this the NADH is and the fadh2s it'll take those high drives to the electron transport chain and what will come out of the electron transport chain ATP so generate ATP so you'll produce a tipi now in a situation and which our body has what low blood glucose levels this pathway is not going to be utilized as much our body switches gears so now this is our primary I told you guys again let's write it above it glucose or carbohydrates and generous let's write go above like this this is our carbs this is our first source of fuel it's our primary source of fuel this is the one that we would actually go to first we want to go to carbs first but in a situation in which these are not available or they're very limited amounts our body will switch to a second source of fuel and that second source of fuel is going to be fatty acids okay so again let's write it up here this is our second source of fuel now what happens with these fatty acids you know these fatty acids they undergo specific process that you guys have already talked about remember beta oxidation beta oxidation was that four step process that was literally generating acetyl co a now if we're having excessive breakdown of fatty acids because our glucose levels are low in our ATP levels what was going on with our ATP levels because there was low glucose there was low ATP our cells are going to require that it could be from many many different activities transport pumps contraction even generating DNA and transcription translation tons of processes so our body switches gears it goes to the second source of energy squeal and starts breaking down lots of fatty acids and again what is this process called when you're breaking down these fatty acids this is called beta oxidation so beta oxidation is the process in which there is actually going to be the breakdown of fatty acids into a CoA and we already talked about in an individual video now what happens as a result of making lots of about breaking down these fatty acids what do you make a lot of a lot of acetyl choline so as I start making a lot of acetic away I'm going to have a lot of krebs cycle activity and produce a lot of ATP so again what's going to happen as a result I'm going to have a lot of acetyl co a and then as a result I'm going to have a lot of NADH is a lot of fadh2s I'll go to the electron transport chain and what will happen to my ATP levels it'll go up problem is though when our blood glucose levels are low you remember that mechanism our body does it's called gluconeogenesis where the oxaloacetate can be utilized for what remember the oxaloacetate can actually get converted into a molecule called malate and they can get pushed out of the mitochondria when it gets pushed let's say that for example this is the mitochondria Mitel there malee can get pushed out you can get converted back into a a and then oaa can get converted to a special molecule which was called what what was that molecule called phospho enol pyruvate and then I could get converted into glucose and if you remember what was the enzyme was regulating this step from oaa to pep it was called pep c k this enzyme was stimulating this step so whenever there is low blood glucose levels our body deals with that with trying to make glucose through this process of gluconeogenesis so where's this process here called this process is called gluco neo Genesis okay well as a result then what happens to your oxaloacetate levels if you're utilizing that oxaloacetate to make glucose one whose concentrations start going down yes and look what happens when his concentration starts going down is his concentration starts going down this acetyl co a can't react with this oxaloacetate anymore because there's very little of them so very little acetyl co a is going to react with the Oh a and you're going to make less citrate now what happens in response to this very little citrate our body decides to shuttle or shift this acetyl co a production into a different molecule so now look what happens this acetyl co a is going to go into a special pathway I'm gonna have a lot of a CO CO is here what I'm going to do is I'm going to take an acetyl co a here and another acetyl co a and I'm going to use them together okay so I'm going to take these two acetyl co a z' and i'm going to infuse these two acetyl co a s together and as i fuse them one of the co ways is going to have to come off and so out of this reaction will come off a co enzyme a so I'll lose the coenzyme a in this process another thing that's happening is what enzyme is triggering this pathway because this enzyme isn't just occurring like automatically there has to be an enzyme that's triggering this pathway this enzyme is called a CE tool acetyl co a Asil transferase okay so this acetyl co a a co transferase enzyme is doing what it's taking the acetyl co a and the other is you equate and fusing them together and as a result what is the molecule that you're forming as a result you're going to form a molecule called a cito acetyl co a so what's this new molecule here formed it's called molecules called a cito a see till Co a so I went from two acetyl co a z' reacting with the presence of acetyl co a acyl transferase and i'm going to get rid of a coenzyme a and i'm going to form a seat osc2 co it it's just these two guys fused together without a la then I'm going to take this Osito Osito call a and I'm going to do another special reaction with it I'm going to add in another color okay so I'm going to add in another Co a another acetylcholine so look what I'm going to do here I'm going to take this acetyl co a and I'm going to add in another acetyl co a so what I'm going to do is might take a seat alcoa here and I'm going to add this poppy in right there and I'm going to get rid of another co a so I'm going to lose another co as a result of this so what am I going to do I'm gonna lose a co a as a result of this coenzyme okay then when I have this Osito Osito co a combined with another acetyl co a I'm going to get a new molecule and this new molecule that I'm going to form as a result of this reaction is going to be specifically cold they abbreviate it I'm going to write down the abbreviation but I'll write down the name also just for the heck of its called hmg-coa so HMG co a stands for 3 hydroxy three methyl glue Terrell call a so now you guys see why people refer to this as hmg-coa because it's a heck of a name okay so hmg-coa is going to be formed by what taking a seat ofc toko a reacting with another acetyl co a because you have tons of those at C the Kois why not use them up so now when we do that when we take this acetyl acidic away put in another acetic away we form h mg color which is also referred to as 3 hydroxy three methyl blue taro co a some literatures because the 3 carbon is usually also the beta carbon you might hear it written as beta hydroxy beta methyl glue taro co egg but we can just refer to it as hmg-coa now what enzyme is catalyzing this step the enzyme catalyzing this step is specifically called HMG call a synthase H M G Co a census if you don't remember any of these enzymes please remember this one because this enzyme is the rate-limiting enzyme so this step right here that we're going to right now this is called the rate limiting step so the rate limiting step okay so it's one of the most important steps within this process now this HMG co what's going to happen with him this hmg-coa is going to do something really cool he's going to get acted on by another enzyme okay in this enzyme that's going to work on this hmg-coa okay we already know the name of this molecule okay but again you can refer to as hmg-coa or three hydroxy three methyl blue Tara : but look what enzymes coming into this area this enzyme is going to stimulate this step now you're probably going to be like I don't get why we keep doing this act but it's all part of our body's amazing way to deal with this so yeah we put in a co a in this step we're going to get rid of it we're going to get rid of an acetyl co a so what we're going to do is we're going to take an enzyme here and we're going to cut this molecule with a molecule called H M G Co a lie ace so this HMG co l ayase is going to be an enzyme and this enzyme is going to cut the hmg-coa or the three hydroxy three methyl glute arrow a and it's going to pop out an acetyl coline so it's going to pop out on a fetal Cola and as a result and this new molecule that I'm going to get is going to be referred to as acetyl acetate okay so I'm going to get a Seto acetate out of that reaction now one more thing can happen as a result of this this acetyl acetate can get put directly into the blood so this is see the last take and literally get put right into the blood but some of this acetyl acetate is converted into another model to another type of ketone body because this is one of the ketone bodies let's actually write that this is actually one of the ketone bodies so this is the one of the types of ketone bodies that we're going to call it that's going to be utilized for energy for the muscles and for the brain right now acetyl acetate has a special mechanism here what it can do is let's do with a different color here I can take this acetyl acetate and I'm going to have this molecule called NADH come into play this NADH is going to drop some hydrides off onto this acetyl acetate and convert him into in AD positive right because it's going to drop the hydrides off onto the acetyl acetate so this acetyl acetate is going to get reduced it's going to get reduced to a molecule refer to as beta hydroxy butyrate okay so you're going to get beta hydroxy butyrate which is going to be one of the Akito body so this is the other team KO body that you can develop here this is the other ketone body right and what can happen this beta hydroxy butyrate can get spit right into the bloodstream so we can spit this into the bloodstream so what are the two things that we spit into the bloodstream out here we've put into the bloodstream two types of ketone bodies and again what are those ketone bodies that we put in one is Osito acetate the other one is going to be beta hydroxy butyrate these two guys can get taken into this actual muscle cell or again one other cell it can be taken into the muscle cells or they can be taken into the brain cells right so that our neurons can utilize that okay none one more thing that I need to point out you know this is fetal acetate okay we reverse this acetyl acetate be converted into this beta hydroxy butyrate you had to have an enzyme what did I have here NADH to NAD+ you know that whenever you see that there's a dehydrogenase enzyme and I'm synthesizing beta hydroxy butyrate so this enzyme here must be what do you think this enzyme is called this enzyme is called beta hydroxy butyrate dehydrogenase and this enzyme is stimulating this step okay the beta hydroxy butyrate dehydrogenase is converting acetyl acetate into beta hydroxy butyrate and then it's going to push into blood one thing we need to realize again these molecules are your ketone bodies they can get taken up by muscles and by the brain now something happens with us a co acetate there's another enzyme for the acetyl acetate when it's in the blood let's show this acetyl acetate here let's say that we spit some acetyl acetate right here also from this process this acetyl acetate can be acted on by another enzyme and this enzyme is called acetoacetate decarboxylase this enzyme is called a seto acetate D carboxylase and what it's going to do is it's going to rip off a carbon off of the acetyl acetate now generally acetyl acetate is a four carbon long structure so this is about four carbons but what I'm going to do is I'm going to rip off a carbon and when I do that I turn it into a very very dangerous molecule inside of our body and that dangerous molecule that can actually cause certain problems is called acetone why is that relevant okay in certain people who have uncontrolled diabetes mellitus type 1 one of the diagnostic tools is to smell their breath you know whenever someone's having uncontrolled diabetes mellitus and they're having a lot of this keto metabolism they're going to be having a lot of acetones are going to try to breathe off now you know why these I'm mentioning that is because the acetyl acetate and beta hydroxy butyrate are naturally acidic you might have heard of this term in chemistry these generally have a PKA around 4 to 5 which is meaning that they're pretty acidic okay so if it has a PKM around four to five normally a good buffer is going to be plus or one minus the pH right now if this pKa of these ketone bodies are excessively you know low it can be very acidic what does that mean that means that these ketone bodies can donate protons into the bloodstream and if they donate protons into the bloodstream what does that do to our blood and makes our blood acidic so if it's donating protons into the actual blood stream it's making the blood really really acidic this can lead to acidosis so this can lead to acidosis specifically they refer to it as keto acidosis and again it's because this acetoacetate and beta-hydroxybutyrate generally have a PK around four to five so they're naturally acidic and they can donate protons so one thing you're going to notice with this person who might have prolonged starvation uncontrolled type 1 diabetes mellitus or a very very prolonged Atkins diet they'll have acetone breath a fruity breath because they're trying to breathe it out also they're going to have acidosis their pH might be a little bit low but you can also test this you know doctors don't naturally just go straight by the pH they also go by another test in a way that they can look for this is what's called an anion gap and if they take this person and they see an elevated anion gap well you know usually a blob of approximately 11 million molar this person could actually have some type of acidosis okay whether that be a ketoacidosis or something else generally whenever it's significantly larger than about 11 million molar per liter they can actually say okay this person is a high anion gap we should evaluate that and we'll talk about this whenever we talk about acid-base balance okay now Nataly understand that can be acetone breath there could be acidosis they would have a high anion gap what is going to happen with a cc ttle acetate in the beta hydroxy butyrate besides that okay you know these guys here are pretty interesting they can be utilized by certain tissues but when they are caught whenever there is too much of these whenever there is excessive excessive excessive amount of these molecules are here too much of this beta-hydroxybutyrate and too much of this acetyl acetate there's a particular part of our brain stem and that particular part of our brain stem is called the area post Rima it's where the chemo trigger zone is whenever there is excessive levels of this acetyl acetate and beta-hydroxybutyrate these molecules can stimulate the area of post streamer within the trick emo trigger zone you know what that's going to do is going to trigger vomiting and when they're vomiting excessively what happens to these people in if they're vomiting excessively what are you losing you're losing a lot of fluid so another complication that can come with these individuals is not just acetone breath not just a high anion gap not just acidosis but also let's add to the list vomiting in the danger with vomiting is that if they're vomiting too much this can lead to hypo Volumnia which is low blood pressure right and if this gets significant if hypovolemia become so much to where the person becomes dehydrated significantly it can lead to leading the person into a comatose state right so they go into a comatose state so it's extremely dangerous on top of that one of the ways that our body tries to be able to deal with this acidosis is that we try to do three different mechanisms one is we have a specifically a bicarbonate carbonic acid buffer system but that doesn't last for too long it usually gets drawn up within about you know a couple minutes and maybe even seconds but our respiratory system we're trying to hyperventilate so if we're going to be consistently trying to hyperventilate to get some of that actual co2 out decreasing the carbonic acid and decreasing the proton levels that tries to be able EBA the problem so you're also going to see within these people what's called a classical sign which is called Kussmaul breathing so they're going to have custom ole breathing and custom all breathing is basically where and I think there's two lessons in this sorry Kussmaul breathing it's going to be whenever they're having excessive and very very deep and rapid inspirations trying to be able to breathe off some of that acid in the form of co2 okay and also if they're having a elevated levels of this acetoacetate and beta-hydroxybutyrate in the blood eventually they're going to spill that out into the urine and so what's one of the other signs that you can find within this person you can also find what's called keto urea which just means that elevated ketones within the urine and that could be some diagnostic signs of this okay now what can we do with these molecules now now that we've generated them within the liver now we have to take it to the organs that are going to utilize it which is the muscles and the brain how do they do that exact opposite of what we just did so let's fly through that now first off we have to start up here with who technically we have to bring this beta-hydroxybutyrate up here first and then we'll bring this acetyl acetate down here and I'll explain why in just a second Osito acetate okay and then up here we're going to have beta hydroxy butyrate okay if you guys remember from one of the steps there the last steps now we're just going to be working our way backwards if we want to go from beta hydroxy butyrate to acetyl acetate you remember this was a reversible step so going from acetyl acetate to a beta hydroxy butyrate I had to do what I had to unload nadh --is well to go in this way I need to generate NADH s so this would be the exact opposite reaction I'll be taking nad positives and generating na BHS okay what else is going to happen let's get this air out of the way just now that we know that what enzyme was controlling this step you remember this was a dehydrogenase because anytime you see NADH no dehydrogenase so it's called a beta hydroxy butyrate what D hydrogenase enzyme and this enzyme is stimulating this path to make acetyl acetate now acetyl acetate can come straight from the blood into this cell now when it's in this cell what's going to happen to the acetyl acetate the acetyl acetate is actually going to get converted back into another molecule that next molecule that we're going to make is called a cito acetyl co a so we're going to make another molecule which is called a cito acetyl co way now in order for this to happen something really weird is going to happen because if you remember the only thing that was really different whenever we were going from acetyl acetic away we had to go to an intermediate which was called HMG co a and then two acetyl acetate we're going to go straight from acetoacetate to acetyl acetyl co a so we need a different intermediate in this case remember from the Krebs cycle you generate a specific molecule so let's say here's our Krebs cycle with your acetyl co a and then you go through the Krebs cycle you know there's a specific molecule from the Krebs cycle that we actually can generate for this pathway it's called sucks an isle CO a if your that CO a there there's no kolya there guess what he does he comes into this process and drops off his Co a because he's going to come out as Sox innate then when this happens in order for us to be able to take this acetyl acetate into the acetyl acetyl co a we had to transfer a CO a onto this guy so when we're transfer the co a onto this guy then we're going to get the acetyl acetylcholine then the Osito acetyl co a is going to be broken down broken down into what a fetal Co a and acetyl co a oh man that's awesome so we can take this acetyl co a this acetyl acetyl co a and we can break it down into two different types of molecules now what is the name of the enzyme controlling this step the enzyme controlling this step is specifically a special enzyme called Sai o for race so the style for race enzyme was catalyzing this conversion of acetyl acetate to acetyl acetyl choline then the acetyl acetyl co a was getting broken down Wendy was getting broken down it was getting cleaved into two different structures this is Utica lay and this is Utica Way so what must have happened here I must have had to transfer a coenzyme a in there somewhere so I had to bring a coenzyme a in there so I must have had some type of acetic away acyl transferase enzyme so I must have had some enzyme in here is called a acetyl co a Asil transferase enzyme who is stimulating this step then I have these acetyl co lays these acetyl COAS we're doing what with these acetyl co ways we could actually bring them down where we can bring them down into the krebs cycle out of the krebs cycle what do I generate when I generate from this I generate nadh s I generate fadh2s i generate ATP wouldn't be the same for this guy also yes so this guy's also going to go through the Krebs cycle when he goes through the krebs cycle what's he going to give up he's going to give away again nadh s fadh2s as well as so many TP and then what can these NADH is in these fadh2 to do these can come to the electron transport chain and what happens at the electron transport chain specifically remember these molecules come to the electron transport chain and they're utilized to make what so these guys over here will come to the electron transport chain and we utilize to make ATP so as a result you'll produce ATP which is the overall goal oh it's beautiful okay so now that we've done that we basically took those ketone bodies that we took from the liver that we synthesized in the liver brought them over into the muscle skeletal muscles cardiac muscles and brain and then you utilize them for energy and why the question is why is the brain using that when it can't use like fatty acid because fatty acids have a hard time being able to cross the blood-brain barrier ketone bodies can okay so now that we brought the ketone bodies in we can make ATP and now the brain is satisfied because it can produce some ATP from this reaction okay now I hope all of this made sense and engineers I hope you guys enjoyed it I know it was a lot of information thanks for sticking in there with me if you guys did like it this video hit the like button comment down the comments section and please subscribe I ninja nerds until next time

Channel: Ninja Nerd Lectures

Views: 200,731

Rating: 4.9755974 out of 5

Keywords: ketone metabolism, metabolism

Id: BlR9DkUAUkI

Length: 31min 23sec (1883 seconds)

Published: Thu Jun 01 2017