in this lecture we're going to talk about metabolism metabolism is the totality or the entire organism's chemical reaction and this lecture we're going to talk about metabolism in general and in the next few lectures we're going to talk about specific aspects of metabolism in particular we're going to talk about cellular respiration this is how animal cells and plant cells as well derive energy from stored sources of energy like sugars as well as photosynthesis how plants and other photosynthetic organisms store energy that they gain from light but for now we're going to talk about metabolism in general so all living cells are chemical factors many chemical factories an example that we've talked about of things that are happening in a cell sodium potassium atpase remember that this is the pump that takes out three sodium ions this is the outside of the cell this is the inside of the cell and brings in two potassium ions while expending atp right converting atp into adp and we'll talk about this process a little bit later in the lecture the conversion of atp and to adp but that's a a chemical reaction that is occurring within the cell another example is shown here on the left these firefly squids they glow or they have bioluminescence so they use chemical reactions to generate light when they're in the deep oceans and they can use it as a mating ritual as well as to ward off predators so these use chemical reactions to generate light which is called bioluminescence and they use it for mating rituals as well as to ward off predators and both these processes right require energy energy required and energy required for this process comes from extracting energy stored in sugars and other fuels and that is metabolism so metabolism is extracting stored energy from sugars and other fuels and in this lecture we're going to talk about how matter and energy flow during this process of metabolism and how it is regulated so again metabolism it's the totality defining metabolism totality of organisms chemical reactions and most of these chemical reactions occur in stepwise fashion so here we have a starting molecule that will be converted via one reaction to molecule b which will now be converted to molecule c in a reaction two and reaction three will convert that into product d so this occurs in a stepwise fashion so most reactions occur in stepwise fashion and we can break down metabolism into two major pathways one it's called a catabolic pathway and this is the breakdown pathway where molecules are broken down into smaller pieces and the energy stored in that is extracted or released an example of this is called cellular respiration and we'll dedicate an entire lecture on cellular respiration but let me just give you the gist of it it's the breaking down of sugar glucose to [Music] carbon dioxide and water to smaller pieces and the energy stored is released and that energy is that's released is used by the cell to carry out these reactions the second pathway is the anabolic pathway and it's exactly the opposite of the catabolic pathway it's a biosynthetic pathway meaning it makes bigger molecules from smaller molecules and it uses energy an example of that is building dna molecules from nucleotides right polymerization dna molecule from nucleotides another example is building proteins from amino acids and we can grow this list on and on and on but let's just stop right there and this process of studying how energy flows through the living organism is called bioenergetics bio energetics study of how energy flows through living organisms but what is energy let's talk about energy energy is in essence is the capacity to cause change right in the simplest terms is the capacity to cause change and how does it cause change it can it has the ability the energy has ability to rearrange collection of matter is the ability to rearrange and there are two forms of energy kinetic energy right that's the energy of movement anything that is moving has kinetic energy an example of that would be thermal energy when things are moving they'll heat up and is the kinetic energy associated with movement right with the random movement another example is light energy that is also kinetic energy okay but there's another form of energy it's that is not kinetic energy it's the energy that an object or matter possesses because of its location or structure and let me explain that here is a diver right has climbed up the these rams these stairs and came up to this top of this diving board so he or she has the now a potential to drop and make movement so this diverse has potential energy has stored potential energy and when this diver finally dives off they're actually dropping and converts potential energy to kinetic energy the energy of movement and splashes in and the cycle repeats again right and this diver when they climb they're actually doing work to actually put energy into the system that's stored as potential energy okay so potential energy is the potential to do work for instance and a good example is a water behind a dam right we store water in a dam so when we open the floodgates it can turn the turbine and generate electricity molecules also have potential energy and they can be stored as chemical bonds electrons in bonds between atoms and this will be chemical energy and kinetic energy and potential energy are always transformed right between the two as you can see here in the diving board this potential energy is converted or transformed into kinetic energy when the diver decides to dive off right so there's transformation that can occur between these two forms of energy and the study of the energy transformation is called thermodynamics because thermodynamics was the study of energy transformation and there are two laws of thermodynamics and let's talk about that the first law of thermodynamics as shown here in this diagram of the bear eating a fish is that energy can be transferred and transformed but it cannot be created or destroyed energy can be transferred or transformed but it cannot be created or destroyed and this is also called the principle of conservation of energy also known as principle of conservation of energy so as an example when plants perform photosynthesis again we'll learn about that in a great deal a little bit later but they convert light energy into chemical energy and they act as energy transformers not energy producers right for example plants and photosynthesis convert light energy to chemical energy so there are energy transformers not producers so an example of this bear eating the fish fish has complex chemical bonds stored as chemical energy and when the bear breaks that down it releases energy when it digests the food right through through catabolism and it's converting this potential energy right stored chemical energy to kinetic energy running or moving let's talk about the second law of thermodynamics it states that every energy transfer or transformation increases the entropy of the universe now that sounds very abstract and we'll we'll talk about it in a way that we can understand but let me write that down first every energy transfer or transformation increases entropy of the universe first let's define entropy what is entropy it's the measure of disorder or randomness an example is your neat bedroom in your dorm room becomes messy over time that exemplifies increased entropy things going more into disorder things going more into randomness so with each transformation or transfer of energy there's actually a loss of usable energy and what that means is that not all the chemical energy that the fish provides right as shown here by the bear eating the fish is converted into energy for moving some is lost to loss of body heat right here some is lost to breaking down the molecule so they can be exhaled so it's not a perfect system with each transfer or transformation there is loss reusable energy and this loss of usable energy this loss goes into creating more disorder or more randomness in the universe because it takes energy to organize things and spontaneously it will want to go into disorder let's talk about this whole idea of spontaneous processes so spontaneous process right can occur without an input of energy in the spontaneous process by definition it must increase the entropy of the universe things that happen normally will always lead to more disorder in the universe it must increase entropy in the universe but it doesn't mean that because it's spontaneous that it's fast don't get those two things confused does not mean fast or quick right they are fast spontaneous processes like explosions that's fast but car rusting it's spontaneous but it's slow all right so these two laws of thermodynamics apply to the universe but as biologists we want to know if the reactions occur spontaneously within a cell and which ones require input of energy from the outside and in order to better understand and have a better discussion about this we first need to define what energy is the whole idea of energy was actually coined by gibbs in the late 1800s and that's why it's called gibbs free energy so g is gibbs free energy this is now we're trying to quantify energy within a system this is also just called free energy and this is a portion of the system's energy that can perform work when temperature and pressures are uniform so this is the portion of a system's total energy that can perform work and that's what we're interested in as biologists right when we have chemical reactions what portion of that energy can be used to perform work we're not too concerned about the total system's energy and when this energy transforms or transfers there is a change in this free energy and we talk about delta g which is the change and free energy and delta g is defined as delta h which is the system's enthalpy and we'll get to that in a minute minus t temperature delta s and delta s is the system's entropy so h delta h is the change in systems enthalpy and in biology enthalpy is the same thing as total energy same as total energy delta s is the change in systems entropy systems disorderliness and t is temperature measured in kelvin absolute temperatures and why do we care about this delta g so once we know the delta g for a process for a chemical reaction we can actually predict whether that process will be spontaneous or not once we know the delta g a process we can use it to predict whether that process will be spontaneous what are the delta g values for spontaneous reactions it's the negative ones so only processes with negative delta g are spontaneous and for delta g to be to be negative either delta h is negative or t delta s is negative or both positive or zero delta g is never spontaneous so let's talk a little bit more about this delta g right the delta g is in this equation but again as biologists we aren't too concerned about calculating the entire system's enthalpy in the entire system's entropy to try to figure out whether a reaction will be spontaneous or not within a cell we are more interested in the beginning and end states of free energy and use that to determine delta g okay so delta g is g final state the free energy of the final product compared to the to the free energy of the initial state okay so so delta g can be negative if there's a loss in free energy between the initial state and the final state between initial state and final state and if the initial g is high it means it is less stable high free energy means it's less stable because it's wanting to give up more of that energy and as a converse low g is more stable so what does that mean let's use these examples on our left to try to talk about this here's a example of a diver right has higher g because they put in potential energy there's more free energy in the system in this diver and when the diver dives off converts potential energy to kinetic energy there is actually now results in a lower g or lower free energy another example here is diffusion let's say we put a molecule or a drop of dye in water and they will diffuse right via random motion they will diffuse until they're equally spaced apart and they're randomly dispersed so this die molecules when it's first put in sitting in a cluster it has higher g it's more unstable so it's going to go spontaneously to as stated here spontaneous change into a state where there is lower free energy more stable and the same thing can be said about chemical reactions if a chemical has high free energy it will spontaneously go to state of low free energy this is glucose up here broken down into co2 water molecules but again the fact that it's spontaneous does not mean it's fast right this can be this diffusion can be relatively fast but this reaction is probably slow without the help of enzymes and we'll talk about enzymes later right this diver will eventually if the diver is up there infinitely long will eventually fall off by themselves this will naturally diffuse and given enough time glucose will break down into these products down here to smaller molecules so each of these systems that's outlined here or exemplified up there will go towards lower energy greater stability and that's the relationship between free energy and stability okay an equilibrium is the state of lowest free energy equilibrium state of lowest free energy given enough time this diver will fall off and stay in the water given enough time these molecules of dye will diffuse and be equally randomly dispersed in water given enough time this glucose will break down into smaller molecules and that's when it gets to that point this reaction no longer goes forth right from the high energy to low energy state free energy states and that's equilibrium and reactions can go back and forth right can they can go to state of more high energy a more free energy but the rate of forward and backwards reaction is the same but same about at the same rate and because equilibrium its lowest free energy state to get things out of equilibrium will have positive delta g's you'll need to put energy into the system therefore it's not spontaneous so any change from equilibrium we'll have positive delta g values therefore not spontaneous it will require energy to do so and because system at equilibrium cannot spontaneously change it cannot do work because work requires energy to come out of reaction the process that is spontaneous can only perform work so let's talk about reactions that are spontaneous and can do work versus reactions that are not spontaneous that require work and that brings us to free energy and metabolism and there are two types of reactions in metabolism the exergonic versus endergonic reactions exergonic reactions are called energy outward that's what it means exer outwards those kind of reactions proceed with a net release of free energy as shown in panel a right this was a reactant which the total free energy was some some point and when the reaction occurs the product has lower free energy so where does that energy go well it's released and in chemistry you've probably heard of this as exothermic reactions chemists call this exothermic reactions and of course delta g is negative thus it's spontaneous and it's energetically favorable but again it doesn't mean that it goes fast but it's just favorable and they're genetically favorable means the energy this reaction will occur and the size of delta g determines how much work is done let's talk about an example of glucose c6 h12 o6 in the presence of six oxygen molecules will break down into six carbon dioxide plus six water molecules and the delta g of this reaction is negative 686 kilocalories per mole so with each mole of sugar which is about 180 grams of glucose 686 calories of energy is made available for work okay endergonic reactions are energy inward it takes energy it absorbs energy from the surroundings and it stores the energy that it takes from the surrounding in molecules and chemists call this endothermic reactions and the delta g is positive because it's positive it's non-spontaneous and the example we can talk about is the reverse how we make glucose or how plants make glucose it takes six carbon dioxides and water to produce six oxygen molecules and a molecule of glucose and the delta g is positive 686 kilocalories per mole so it takes 686 calories to produce a molecule of glucose now this is non-spontaneous it will never happen by itself if you put carbon dioxide and water in a tube and let it sit there it will never make a molecule of glucose by itself so it requires energy to be put in so how do plants do this well the the energy source here is light plants capture light energy to use to create sugars so let's think about how these reactions are occurring within a cell and when you talk about isolated versus open systems so reactions occurring in an isolated system here's an isolated system there's nothing coming in nothing leaving so it's a self-contained unit right initially when there's more water on this side than this side water will flow down and the delta g is going to be negative it's going to be spontaneous event and you can generate electricity by that release of free energy by water flowing down but eventually the system is going to reach equilibrium right delta g will become zero no work can be done from a system that's in equilibrium so you cannot generate any more light from this down in an isolated system so reactions in isolated system cannot do work after they reach equilibrium okay and a cell that reaches metabolic equilibrium is dead right if you cannot do if you cannot generate energy you cannot do work cells that can't work die so the fact that metabolism as a whole is never at equilibrium is one of the defining features of life fact that metabolism as a whole is never at equilibrium is one of the defining features of life so how can a cell have metabolism that is not at equilibrium well you have to have and cells do have an open system open system as opposed to the isolated system there's a constant flow of materials in and out and as you can see from this example here in b an open system where water is being continuously added to this tank on the left and there is a spigot an open end where the water is always draining so there's always going to be a free energy difference between the left side and the right side and it's going to continuously flow delta g is going to be negative and light energy can be harvested and you can produce light and that's the way cells work right the byproducts are removed from the cell building materials are always fed to the cell so that the cell can never hit metabolic equilibrium but instead of having one input one output this catabolism this catabolic pathway occurs in multiple steps as shown here right there is a multiple step converts to one converts to another converts to another deriving free energy out of the system in a stepwise fashion catabolic pathway releases energy in a series of reactions and we've been talking a lot about this work this free energy released being used as work let's talk about work cells do three main kinds of work one is chemical work which is performing reactions cells also do transport work that's pumping substances across the membrane against the concentration gradient an example of that is the sodium potassium atpase and third they do mechanical work and that is physical movement like the beating of a cilia or muscle so where does this energy come from to do this work so this is where we're going to get into what's called energy coupling so this is where the energy released by the exergonic reactions are used to do work use organic reactions to drive and organic ones these energetically unfavorable reactions and the molecule that's responsible for this energy coupling is atp mostly so let's talk about atp in a little bit more detail atp as you know is a nucleotide right it's an adenosine right with the sugar with the base adenine and phosphate groups this the atps happen to have three phosphate groups attached to each other and it can be broken so bonds of phosphate groups can be broken by hydrolysis you bring in a molecule of water and you can break that bond right here and you get a release of inorganic phosphate and it releases energy right the delta g is negative for this reaction it is an exert organic reaction this atp plus water goes to a dp diphosphate plus inorganic phosphate and the delta g obviously is negative because it's an exogonic reaction it's negative 7.3 kilocalories per mole and the energy it releases by losing this phosphate is somewhat greater than the energy most other molecules can deliver the energy it releases this negative 7.3 kilocalories per mole on losing phosphate somewhat greater then most other molecules can deliver why well this this phosphate bond isn't high energy on its own it's that the three phosphate groups in close proximity leads to instability instability is high free energy right because the phosphate groups actually have negative charges right negative negative negative negative and they all want to repel each other and by trying to squeeze all these negative charges together in one place there's a high energy wanting to repel each other as you probably played around with magnets if you try to put two negative ends of a magnet together it's really hard to get those two magnets to actually contact each other right so mutual repulsion of negative charges contributes to high free energy so how does this hydrolysis this reaction of going atp into adp how does it actually perform work well here's an example of a chemical reaction here's a glutamic acid being converted to glutamine glutamic acid into glutamine with the addition of an ammonia group this reaction the delta g of this reaction is plus four kilocalories per mole so that it's not spontaneous right because it has a positive delta g the atp breaking down into adp and inorganic phosphate releases 7.3 kilocalories per mole right so actually there's an intermediate step the atp actually transfers one of the phosphates to the glutamic acid so it's called a phosphorylated intermediate and then when the ammonia comes in that inorganic phosphate pops off so let's say let's state the phosphorylated intermediate that actually bridges this delta g to this delta g right otherwise there'll be two reactions occurring side by side as opposed to being one reaction but the really the atp hydrolysis releases negative 7.3 kilocalories per mole so you can now look at the net result of this reaction to convert glutamic acid to glutamine it takes 3.4 kilocalories but hydrolysis of atp releases 7.3 calories so the net delta g is negative 3.9 kilocalories that means now it's spontaneous because it has negative delta g right this is how hydrolysis is linked to doing work to convert non-spontaneous reactions into energetically favorable spontaneous reactions and atp again the intermediary between this to convert energy so this is an example of atp hydrolysis in chemical work right let's talk about atp hydrolysis in two other forms of work transport work and mechanical work so here's an example of atp hydrolysis driving the sodium potassium atpase right atp in sodium potassium atpase also known as a pump and atp is also the bridge between for movement where atp hydrolysis moves motor proteins so the energy released by atp moves these legs so to speak around and it can move left right left right along the cytoskeletal tract so this is an example of mechanical work so we've been talking about atp hydrolysis the usage of atp but how are they regenerated how is atp actually made let's talk about just briefly atp regeneration so as you can see from here right the hydrolysis of atp releases energy right and that's done that's used to do work but this is actually recycled the energy required to phosphorylate adp right you're putting phosphate group back on adp phosphorylate adp comes from those exergonic reactions that's catabolism right for example sugar being converted into carbon dioxide and water will lead to atp generation and we'll talk about that again and this adp phosphorylation is actually really fast this the atp cycle is really fast and just to give an example right a working muscle recycles the entire pool of atp in less than a minute that translates to 10 about 10 million atp consumed per second consumed and regenerated per second if there was no regeneration then humans would actually use up nearly their entire body weight in atp each day if no regen then humans will consume their body weight and atp each tank and the delta g for this reaction was negative 7.3 kilocalories per mole the delta g for the synthesis of atp is exactly the opposite delta g is 7.3 positive 7.3 kilocalories per mole and of course this is non-spontaneous where does this energy come from well from catabolism as we just mentioned okay so that was metabolism in a nutshell and we'll talk about specific examples of metabolism in the next few lectures