now we're going to talk about a topic that spans multiple organ systems and it's focused on the balance of energy in the body so we've talked about the law of mass balance as applied to other systems for example the regulation of the volume of water in the body you can also apply this idea it's simple arithmetic after all to energy in the body where the total energy in your body is equal to how much you have in it right now plus whatever you take on so through the digestive system minus what you metabolize and we have multiple sources of energy that come from the diet and we can burn fatty acids and glucose and some other metabolites as well in all cases the energy available in molecules to produce atp for intracellular functions needs to be balanced at a particular concentration as it circulates through the body for example glucose glucose if in too high a concentration in the body will produce problems and too low a concentration and we feel depleted and suffer from fatigue so hypoglycemia offers insufficient energy whereas hyperglycemia damages organs such as the kidneys your eyes your nervous system so we really want a goldilocks ideal concentration for glucose in the body not to mention the fact that glucose is not a molecule that is as energy dense as other forms of storage so just in terms of efficiency of storage amount of energy per unit uh mass then fats are a much more efficient way of storing energy so our body is constantly controlling the concentration of chemicals in the body uh that provide a source of energy so where does that control come from how is energy controlled well let's start by thinking about the metabolism side of this equation so we're basically going to step through the terms of the law of mass balance and then look at the control system that monitors and adjusts the concentration of in particular going to focus on glucose all right cellular metabolism we're going to take a relatively simplistic approach to this all the boxes and arrows that i'm going to draw out um well i should say all the arrows that i'm going to draw are potentially a much more complex or they definitely are a much more complex series of biochemical reactions mediated by enzymes but for our purposes we can keep them simple so glucose enters into cells quite readily and is then converted into glucose 6-phosphate this is in the cytosol of a cell now when glucose-6-phosphate is combined with two atp molecules then glycolysis can be performed okay so this is a series of biochemical pathways that yields two atp molecules and two pyruvate molecules and that pyruvate can be used as a source of energy under a couple different conditions but first of all glycolysis the bottom line here is that we made an investment of two atps and we got four out of it in addition to the glucose six phosphate which came from one glucose molecule so with one glucose molecule we get a net two atp seems pretty good pyruvate if oxygen is unavailable in the cell pyruvate can be recycled by the liver to ultimately produce glucose we're not going to talk about that right now but just know that if the partial pressure for oxygen is low pyruvate is converted into lactic acid and lactic acid is then returned to the circulatory system where it can be recycled by the liver if sufficient oxygen is available within the cell then pyruvate is converted into acetyl coa now this is where fatty acids come in fatty acids cannot be used as a substrate for glycolysis but they can be converted into acetyl coa so that is useful if there is sufficient oxygen within the cell because mitochondria which are a cells effectively power plants can take acetyl coa and produce a really high yield of atp so that's first achieved through the citric acid cycle which as far as we're concerned is a big circle and that big circle will yield two atp molecules all right so already we've uh taken acetyl coa and we've gotten as much payout from that one molecule as we got out of glycolysis from a single glucose it also produces carbon dioxide finally the citric acid cycle produces an electron and a proton which then provides the basis for the electron transport system which also requires oxygen now here's the big payoff the electron transport system yields 26 atp molecules so if glucose provided the substrate then we're left with a really high payoff and by the way this series of biochemical reactions explains why we breathe okay oxygen is required here and carbon dioxide is a byproduct of the citric acid cycle that's the reason for the respiratory system and why our circulatory system transports those dissolved gases so the ultimate payout for aerobic metabolism for one glucose molecule is between 30 and 32 atps really good payoff for one fatty acid molecule it's 28 to 30 atp so we can see by the way our glycolysis is often referred to as anaerobic metabolism it has a much less a much smaller yield obviously than the aerobic metabolism and so it's quite desirable to circulate sufficient oxygen so that the mitochondria can achieve this aerobic metabolism okay so you can think of metabolism as being the energetic sink this is what cells do to generate enough atp for all those intracellular activities that we've talked about earlier in the class and now we're going to sort of map out where energy flows in the body so in the cells that's the sink where do we find the energy for this well initially it begins with our diet we eat fats carbohydrates and proteins fats are the most energy rich and then we break down those molecules and either circulate them through the bloodstream or store them away so what's in the bloodstream we can think of as being a pool of energy like glucose glucose will circulate through the bloodstream and then you'll find glucose distributed throughout the body within the cells free fatty acids as we've just seen also provide a source of energy so cells primarily metabolize glucose and fatty acids for energy proteins are broken down and they can ultimately be broken down into the form of amino acids and amino acids can also be converted into glucose we'll get into where that occurs in a moment so we have the digestive system providing these pools of energy and we've already touched on the fact that glucose at too high a concentration can be damaging to your organs like your kidney your eyes and so we don't want to just break down carbohydrates and have them circulating around in the bloodstream same thing with the free fatty acids it's among other things not a very efficient way of storing energy so glucose can be fairly readily converted into a larger molecule known as glycogen that occurs within the liver and in skeletal muscles free fatty acids are packaged into fat stored in fat cells and um and then glucose can also be stored away into fat in those adipose cells so excise glucose is first stored as glycogen we have limited capacity for glycogen storage in our body it's available in the skeletal muscles you can increase your capacity for glycogen storage through exercise and um since that's an intracellular um form of storage energetic storage then it uh it's convenient within the skeletal muscles to be able to convert glycogen into glucose when you're exercising amino acids of course can be built up through the synthesis of proteins and you can think of proteins even though they provide a structural role as ultimately being a source of energy if the body needs it so when the body needs energy then glycogen can be broken down proteins can be broken down and so can fats into fatty acids okay now we're going to turn our attention to the control of glucose so so these pathways by by the way all these arrows do correspond to pathways that can occur in particular cells in the body and those cells reside within muscles fat cells adipose cells and in the liver now these pathways don't occur in all of those organs but the conversion of glucose into fat does occur in all of them um the ability to convert amino acids into glucose occurs only in the liver glucose is stored as glycogen in the liver and then the skeletal muscle so these pathways represent efferent actions uh for a control system okay the the goal here is to deliver a certain concentration of glucose excuse me in the bloodstream and you can think of the pathways that draw from the glucose pool as ways of storing these are pathways for reducing the concentration of glucose through storage and then glycogen the conversion amino acids and for that matter [Music] the generation of fatty acids too are ways of essentially cashing in that saved storage of energy now where is the decision making about the homeostasis for glucose made thus far we've considered a variety of control systems in the body they seem mostly to reside in the brain stem this is an example of a control system that doesn't in fact the net central nervous system doesn't play any role in this control system that we're going to map out where is it well it's vaguely associated with the digestive system the pancreas has cells that serve this function and we've already talked about how the pancreas plays a role in secreting digestive enzymes as well as a bicarbonate to neutralize the acidic [Music] chyme that emerges from the stomach so it has those digestive functions this function is kind of separate it's obviously related to digestion because of the way that food provides a source of energy but it doesn't actually produce any products that make their way into the digestive tract okay so let me be more specific we have two types of cells in our pancreas they're called alpha and beta cells and they both serve as sensors and integrating centers for energy balance with with a particular focus on glucose the beta cells secrete insulin which stimulate energy storage okay that's what insulin does another hormone which you might not be familiar with is called glucagon which is secreted by the alpha cells and glucagon does very much something the opposite of glucose so instead of storing energy it stimulates the release of energy or i should say the conversion of molecules into glucose and so that it's available in the bloodstream so let's consider some specific examples of this so let's just monitor plasma glucose and here we see that after you've eaten breakfast you get this increase in plasma glucose and the magnitude of this increase depends on the nature of the meal if you eat a bunch of sugar then you're basically going to have a huge spike in glucose if you eat you know eggs and toast or something like that depending on the nature of the toast you might have a more gradual rise of more complex carbohydrates take longer to absorb now your beta cells in your pancreas respond to this increase with a surge in insulin that's the signal to the body that this glucose should be stored away and not circulated at high concentrations in the blood where they can cause damage and by storing away glucose that allows your body to [Music] potentially cash it in later on okay this is a way of storing energy so that you don't burn it all up right after breakfast now this pattern gets repeated in the subsequent meal so for lunch you get an increase it might be a larger meal and then notice here that after each meal there's initial increase and then a leveling off okay so that leveling off is indicative of homeostasis okay a negative feedback loop and that is largely being driven by the insulin now the exact shape of these curves depends on the nature of the food and how well your beta cells are functioning then at dinner you might have a very large meal and then you begin your fast that you maintained throughout the night glucagon has a less um predictable pattern of changes in concentration glucagon essentially increases with fasting so you can see it the best here around dinner time before the meal has been eaten you can see that increase in glucagon but glucagon doesn't have as sort of a a temporal response uh to these events and your body actually pays um most attention to the relative constitution concentrations of glucagon and insulin so insulin has the most um rapid influence on the um the concentration of glucose in the body and then glucagon has a more sort of long-term gradual influence and again it's the relative concentration of glucagon to insulin that matters the most all right so that's the output of our control system and we already know that we're talking about alpha and beta cells so let's map out that control system now those biochemical pathways that we see up in the upper right can be included on the efferent end of our control system now insulin release as i've mentioned causes your body to store away glucose in the form of other molecules that are better for storage so in the liver we have glycolysis so some of the glucose is converted into atp through that mechanism the liver has some limited capacity to store glucose this glycogen and then also it produces fat the fat cells of the body the adipose tissue also undergoes glycolysis and in response to insulin there's a conversion of fatty acids to fat finally muscle has a variety of means of sequestering glucose so first of all it burns some to produce atp through glycolysis we have glycogen stores within the skeletal muscles glucose is stored away as fat and you produce proteins in response to insulin so that's a conversion of amino acids into proteins now all of these efferent actions serve to counter plasma glucose okay they act to reduce plasma group glucose concentrations and so these are activated in a fed state after you've eaten a meal glucagon on the other hand acts primarily on the liver and it's there that glycogen is converted into glucose made available into the bloodstream and amino acids are also converted into glucose as well so both of those contribute to the plasma glucose concentration now in order to sense and respond or to make this a control system then we have to add the afferent and integrative portions of our control all right so we have the alpha cells which are responsible for the glucagon release and the beta cells which release insulin and this flow chart maps out essentially the answer to the question that we set out to address which is how is energy controlled but before we conclude there's a disease that i want to talk about which is diabetes and we don't often talk about many diseases but in this case it's quite useful to think about how diabetes squares with this control system that we've mapped out so first of all there's type 1 diabetes and type 1 diabetes is an autoimmune deficiency and this accounts for just 10 of diabetes cases and because the the consequence of this autoimmune deficiency is that it it kills the beta cells in the pancreas then we essentially lose the ability to reduce plasma glucose concentrations so this results in hyperglycemia which is quite dangerous and so we can compensate for that by insulin injections essentially replacing the function of the beta cells by monitoring plasma glucose levels and having regular injections after meals and that essentially rescues the functions even though it doesn't work as well as the natural presence of the beta cells it effectively recovers all these pathways so that your body regains the ability to reduce plasma glucose concentrations type 2 diabetes which in 90 percent of cases make cells less sensitive to insulin this is a little bit more insidious in terms of treatments although it can be less severe in its effects on the body it's created by making the cells less sensitive to insulin so these pathways are reduced and this is linked to lifestyle 80 percent of type 2 diabetes cases are in people who are obese and it's also linked through obesity or indirectly to diet and a lack of exercise a sedentary lifestyle so type 2 diabetes is a real epidemic for americans given our relatively sedentary lifestyle and our poor diet now the treatments are are quite varied there's a variety of drugs but lifestyle changes are generally recommended as a treatment for type 2 diabetes