Metabolic Fuel & Starvation

welcome back to the dirty medicine dirty biochemistry series in this video we're going to talk about metabolic fuel utilization this is a very important topic that is one of the worst to learn because quite frankly it involves looking at graphs and making sense of fuel usage in your brain which is really not something that's taught in medical school all too well so when it comes to studying this for USMLE and comlex it gives med students a lot of unnecessary headaches so my goal in this video is to simplify this complex topic into a very short

high yield efficient presentation so that you'll never miss questions about these relatively basic topics let's get in to metabolic fuel utilization so when I use the term metabolic fuel utilization what I'm referring to is what type of macronutrient or what type of fuel be it fat glucose protein etc is being used at what point during starvation so in order to learn this the best way to approach this topic is to use a graph so on one axis will have the stored energy which is to say how much energy is stored in the form of things

like glycogen fatty acids protein etc and on the other axis we'll have time and I'll mark this axis as we go in days and weeks so that you can see what type of time frame were referring to so how I'm going to approach this is first I'm going to explain the normal physiology of metabolic fuel utilization during periods of starvation and after I use this graph and plot the graph we'll go through a chart and simplify this with mnemonics so that you'll never forget this and that you'll understand the normal biochemistry and the normal physiology

so with that said let's dive right in so the first thing that we need to talk about is what type of fuel source the body uses during the course of starvation up to one day so starvation up to 24 hours so up to 24 hours the body will preferentially use glycogen and specifically it'll break down glycogen through glycogenolysis now remember simplify these concepts by looking at the words glyco jeno lysis your licensing or breaking glycogen so buy lie single occasion you're releasing energy into the body and this is the preferential fuel source used when the

body undergoes starvation up to 24 hours okay so up to one day one day we use glycogen now when you get to one day if you still haven't put any food into your body the the body is going to change which fuel source it's using right it can only use so much glycogen but all of the glycogen stores are depleted after one day so you can survive off of your glycogen stores for 24 hours or one day at which point the body needs to say okay I need to start using some other type of fuel

or else my body's gonna keep starving and keep dying so after the glycogen stores are depleted the body is going to turn to fat and fat will predominately take over as the metabolic fuel that's utilized in periods of starvation after three days so let me pause for a second I know what you're thinking you talked about glycogen being used up to one day and now you're talking about fat being used after three days so what about between one in three days well between one and three days we're actually gonna come back to that time frame

at the end because it's the simplest way to learn this material but so far what I want you to realize is that we glycogen stores get used up until one day between one and three days is another period of time and we're gonna come back to that one now we're at three days so what happens after three days well after three days the main metabolic fuel that's utilized in starvation for three or more days is fat and specifically free fatty acids so look at the red part of the graph here okay that rep that's represented

by fat so fat will slowly slowly slowly decline over the first three days because it's a secondary source of metabolic fuel use in starvation but it's only after three days that fat becomes the primary source of metabolic fuel that is used during starvation so fat really takes over at three days so glycogen can can carry the load up until one day between one and three is something else that we'll talk about at the end of the video and then a three days free fatty acids will take over and they'll go up until one week and

at one week the fat sort of plateaus and the reason that fats Plateau one week is because the next source of metabolic fuel takes over at one week and that source is protein now it's at this point in starvation that the body is actually starting to die okay so if protein is being used and broken down because organs and muscles are dying and releasing protein then the body's dying and in real life this would correspond to death due to starvation so it's at one week that the body's finally has run out of glycogen because it

ran out of glycogen at one day it's ran out of free fatty acids because from three days to about one week it burned all the free fatty acids it possibly could and there's no fat store left in the body and then at one week it says our only option here is to start breaking down organs and breaking down muscle to release protein but if you're breaking organs and breaking muscle then the body's in Devitt ibly going to die because of starvation so look at the blue curve protein stays very constant up until one week the

body really doesn't want to kill itself in order to release metabolic fuel so it's only at one week that you see that protein drop in terms of stored energy and it's right there that protein takes over and because proteins taking over and there's really no fat stores left at one week the red curve plateaus at one week so whatever fat is left on the body is pretty much just gonna stay there and the body's going to die because protein is going to take over and break down things like organs and muscle so let me pause

and quickly summarize before I go over some mnemonics up until one day glycogen is burned so all the glycogen stores can be depleted up to one day of starvation between one and three days is another fuel source that we'll talk about at the end of this video from three days to about seven days free fatty acids are the predominant source of metabolic fuel utilization during starvation and then at seven days or one week protein takes over and organs and muscle are broken down and at this point the body's pretty much dying so how do you

remember this right it's easy for me to throw a graph here and expect you to recall it but what is the dirty medicine mnemonic to help you never miss these questions on test day well here you go instead of saying glycogen I want you to say like one gin like one gin one for one day so instead of glycogen sake like one gin like one gin glycogen one for one day so glycogen stores will be depleted at up to one day okay I told you that free fatty acids take over at three days so instead

of free fatty acids I want you to say three fatty acids three fatty acids will remind you that at three days free fatty acids take over as the primary source of metabolic fuel during starvation and for protein breakdown I want you to think that you are weak without protein and instead of weak being spelled WEA K I want you to spell it like the weak w ee k and this will remind you that at one week and beyond protein breakdown is the primary metabolic fuel source that is utilized during starvation so pretty awesome right guys

glycogen 3 fatty acids and weak without protein really simple easy to remember gleich one jin for one day 3 fatty acids for 3 days and week without protein for one week where protein starts to take over those are the dirty medicine mnemonics that will help you remember metabolic fuel utilization so now that we have all that in mind let's fill in our summary chart to really keep things straight here so first i'm gonna fill in what we already talked about so at 24 hours which is up to one day you use glycogen and we remember

that by saying like Onegin from three to seven days it's free fatty acids and the way that we remember that is by saying three fatty acids and then at one week or more protein is the primary fuel source that is utilized during starvation and the dirty medicine mnemonic there is that your week without protein and week reminds you of one week or more now what's important to note here is what drives each of these processes so for glycogen it's going to be glucagon and epinephrine so when the body is in that first period of starvation

up to one day the glycogen or lysis and other processes that are going on secondarily are primarily driven by glucagon and epinephrine and if you've been studying biochemistry at all they should come at no surprise that when the body is in a period of starvation it's going to release glucagon and epinephrine be it wants to provide fuel for the body to keep going between three and seven days when we're using free fatty acids this is really driven by ketone body degradation and the high-yield thing to remember here is that the brain relies on ketones as

its primary source of energy so when you release free fatty acids you can actually do ketone breakdown okay so ketone breakdown is how we're gonna get the mobilization of the ketones for the brain and then at one week or more this is because you no longer have lipid stores so in the absence of lipid stores you are going to start to break down protein because at this point the body's been starving for one or more weeks it's already broken down all of the fat stores that it had in its body and at this point it

really has no other option but to start to break itself down to release protein now that's everything that we talked about already and all of this stuff corresponds to what I put on the graph on the previous slide but what I haven't talked about yet is that little intermediate stage right between one day and three days one day the up to one day either your glycogen stores have been depleted and at three days and more the free fatty acids take over but what about that little in-between period the reason that I saved this for last

is because in order to understand what what fuel the body is using between one and three days we actually have to refer back to a previous dirty medicine dirty biochemistry video to help you remember something that's extremely high yield so between one and three days the primary metabolic fuel source actually comes from hepatic gluconeogenesis okay and this is driven by alanine and lactate and the reason that this is driven by alanine and lactate is because we're trying to provide fuel source for the brain and I told you that the brain predominantly likes ketones but in

the absence of being able to get ketones we also need to provide the body with some type of fuel and the problem here is that we can't go and do gluconeogenesis normally from the TCA cycle instead we have to provide some source of pyruvate that will go up to glucose and this is where the previous slide or previous lesson that I've already taught you in dirty biochemistry will come into play so let me pause for one second summarize what I'm trying to say hepatic gluconeogenesis will drive the fuel for the body between one and three

days of starvation and in order to do gluconeogenesis we have to first have alanine and lactate providing the fuel remember this slide from a previous dirty biochemistry video this was in the pyruvate metabolism video and what I basically was summarizing by showing you this slide was that there are many different ways that pyruvate can be metabolized it can go to alanine it can go to lactate it can go to oxaloacetate or it can go to acetyl co a but two of these processes specifically lactate and alanine are reversible right there's double sided arrow so you

can go back from lactate to pyruvate you can go back from alanine to pyruvate and once you have pyruvate you can go back up to glucose through gluconeogenesis in the liver so that process is called hepatic gluconeogenesis and you should already be familiar with that but the point of me showing you this slide is to say that between days 1 & 3 if you have lactate generated because you're undergoing anaerobic metabolism or you have alanine sitting around because the body is starving and it's gonna try to grab whatever it can we can use these fuel

sources to turn them into pyruvate and then do gluconeogenesis so this is what happens between days 1 & 3 glycogen stores were depleted up to day 1 and now the body is like damn I need something else what can I use and then it remembers hey I've got lactate I've got alanine let's do some hepatic gluconeogenesis so this is what's happening between days 1 & 3 now how are you going to remember this huh I got a great mnemonic for you so if you've ever done a fast yourself you've ever undergone fasting you know that

beyond one day you're pretty hungry right you feel like crap you're like oh I'm hungry so the mnemonic here is blah I'm so hungry and the BL a in blah tells us that the brain is going to rely on lactate and alanine okay so be forebrain l4 lactate a four alanine blah I'm so hungry I've been fasting between one and three days blah blah PLA the brain relies on lactate and alanine so it's between one and three days that hepatic gluconeogenesis will unwell undergo the biochemical pathway that's the primary source of fuel during starvation it

will be pulling alanine and pulling lactate to provide energy for the brain and you're going to remember this because you say blah I'm so hungry I've been fasting for 1 to 3 days ok so this is the summary chart and this is like 90 percent of the information that you could possibly be asked about metabolic fuel utilization during starvation on us Emily and on comlex I just want to conclude by talking about a couple other high-yield points that sometimes get tied into this topic just to be complete and to make sure that you don't miss

any questions so what are the other high yields that you should keep in mind well here they are and I'll go through these one at a time and give you some mnemonics to help you remember this stuff as well so first point red blood cells cannot use ketones right they've got no mitochondria so there's absolutely no way for them to utilize ketones insulin drives the fed state so when you eat a meal right before you're even in starvation like the normal person has breakfast lunch dinner snacks when you're fed insulin drives the storage of protein

carbs and fats so obviously whatever you're eating is going to have various different types of macronutrients and under a normal state right a normal fed state so the opposite of starvation that state is driven by insulin so insulin is what's you know leads to the storage of protein carbs and fat throughout this whole entire topic always keep in mind that the priority the priority target is the brain and the red blood cells so when the body starving the body is choosing what type of metabolic fuel to use in order to fuel the brain and to

fuel the red blood cells because think about it red blood cells help carry oxygen and if you have a decreased oxygen-carrying capacity what's the point of being in starvation like there's no point in burning any type of metabolic fuel if you're not going to be able to have oxygen because the whole body will lack oxygen and you'll just die anyway so you'll never even make it to one week so the priority target is the brain because obviously the brain controls everything and red blood cells because RBC's are the utmost importance when it comes to oxygen

carrying capacity the last thing that you should know and just know it because it does show up is how many kilocalories are in each macronutrient so one carbon has 4 kilocalories one gram of protein 7 and 1 fatty acid has 9 and I'll give you some mnemonics for all this stuff so remember that RBC's and in a previous video I called them really basic cells so red blood cells are really basic cells so remember that really basic cells have no mitochondria and they're so basic that they can't use ketones insulin insulates the body with fuels

so I always think about insulin insulating the body with fuel which is to say that insulin is what leads to the storage of protein carbs and fat and then as far as the kilocalories per carb protein and fatty acid it's just the number of letters in the word carb protein and fatty acid is how many kcals are in each of those energy sources so carb has four letters protein has seven letters and fatty acid has nine total letters so you can easily remember how many correspond to each of those energy sources but guys I guess

that's all for this video in summary remember the graph remember the high-yield chart if you keep the dirty medicine mnemonics in mind you'll never miss any of these questions so try to keep all this information straight in your brain I know that this topic is not the friendliest when it comes to memorization which is why I gave you a bunch of my awesome mnemonics but if you know everything that I've gone over today I think you'll be really well prepared to tackle metabolic fuel utilization