[Music] hello everyone this is andy from med school eu and today we're gonna finish up our first lecture with the last topic the role of enzymes so here's just a brief description of what we're going to learn about enzymes and how they interact in organisms so first we're going to look at an overview of what enzymes are and what do they do we're going to look at enzyme kinetics enzyme inhibition and allosteric enzymes so let's first begin with an overview of enzymes and what do they do and what are enzymes so typically enzymes are biological catalysts meaning that they speed up reactions chemical reactions in the body but they're not consumed by the reaction they're not used up by the reaction or if they are used up they are regenerated by the end of it so as you can see here they're not consumed and almost all enzymes are proteins some could be natural rna molecules some so some some have catalytic properties however most enzymes in general they are proteins okay and enzymes are critical in for biochemical reactions in all living organisms so now let's let's take a look at why we need enzymes in the first place and what do they do in our body so typically reactions occur spontaneously in our bodies and a lot of those reactions do not need anything for them to happen so they they happen on their own without enzymes without catalysts however they occur at a very slow rate and therefore our bodies and other organisms cannot sustain themselves if if they are producing um products at a very slow rate you know 0.1 of a product per second let's just say however if we if we there are two primary ways to increase the speed of reaction in order to meet our demands so if the demand is um let's say 1000 pro of a product per second this is not even close to what it would produce spontaneously right so what we need is a way to speed up the process of gaining this much product per second it would it will happen eventually but not in the second spontaneously so there are two primary ways to do that one is by increasing the temperature of the reaction so let's let's analyze why we cannot simply just increase the temperature in our body so our core temperatures are in humans 37 degrees celsius right and typically if our core temperature increases even a couple of degrees that means we're sick so and and typically at 42 degrees celsius or more the the human body starts shutting down and or organisms start failing and and the the person dies so why does this happen well because proteins enzymes and other structures they can only be functional at a certain temperature and that's the 37 degrees celsius that's when they are in their in their shape but however when it even increases by just five degrees those enzymes and those proteins that are in our body they denature right they denature and therefore our or our organs can't function and we have a full system failure and the person dies so another way to increase the speed of reactions is going to be through enzymatic catalysis and these are enzymes that do not increase the temperature but they facilitate the formation of products and they do it at a much faster pace so the products would form 10 to the five-fold or even 10 to the seven-fold on average so that's how much they speed up the rate the rate of the reaction where they're not consumed they do not increase the number of products they simply increase the speed at which the products are made and it's important to know that enzymes are also very specific for their substrates so they cannot simply bind all kinds of reactants together they are only specific for certain substrates and there are specific enzymes for each type of a reaction all right so now let's take a look at a diagram and really see how the reaction occurs and what type of effect the enzymes have visually on the diagram so first of all let's let's mark down some of these terms here that's delta g and that's simply the free energy of of activation so here we have the reactants here we have the products and this is the reaction as it goes so in order for the reactants to become the products they must undergo a certain state and this this state is called the transition transition state in the transition state the reactants come between something between a reactant and something between a product they're right in the middle so from this point on they can go either this back to the reactants or they can proceed and the reaction occurs and they become the products but this is the critical part where the reactants must cross in order to become the products and this this is called activation energy that's the energy needed for the reactants to be activated in order for them to proceed with the reaction and become the product so here we call this delta g transition state and same with this one delta g transition state now this one the big diagram here would be without no enzyme so no catalysis and this line right here is going to be with enzyme all right so let's see let's see what happens without the enzyme look at how much more energy is needed for that reactant to become the product now without the with the enzyme what happens is it lowers the activation energy it facilitates for for the activation energy to go to go down and it's much easier to convert the reactants into products and therefore it occurs at a much faster pace now note that the amount of products that's formed does not change it the same thing occurs in both types of reactions nothing changes the amount of product is formed the same however the reaction the speed of it happens a lot quicker because of this lowered activation energy so here i have the definition of delta g and it is the amount of energy needed to convert one mole of reactant from the ground state so this is the is the ground state to the transition state right here so that's the delta g that we have marked here and as you can see it's significantly lower it's significantly lower here with the enzyme present so again in summary just what we just learned about the diagram is that enzymes increase the rate of the reaction it happens faster because it decreases the activation energy so it's easier to form the products from the reactants and enzymes do not change the position of the equilibrium so if we are to make product if we are to make one mole of product a it does not suddenly increase the amount of product that's made it simply made faster at a faster rate so let's take a look at uh an example that i drew of what kind of happens with enzymes so this is an enzyme and what they sort of look like i mean they're all in one way or another are different however this is just a general outline of of how it occurs so here we have an enzyme in white and as you can see this enzyme has this active site so we can label this active site active and this active site binds the substrate so this would be the substrate and they can perform and facilitate all kinds of reactions so this substrate has one unit of uh let's just say this is a disaccharide and there's one monosaccharide another bonus accurate this is one two right so we got two disaccharides and they should be broken down into just a monosaccharide so the body can use it for energy like two glucose molecules for example and what happens is they make contact with this active site and this facilitates it to be able to to be broken down a lot quicker and they go their separate ways as monosaccharides all right so next let's talk about enzyme inhibition and what are inhibitors and what do they do to enzymes well inhibitors are exactly what they are in the name they inhibit the enzyme activity so their compounds they could be proteins they could be other enzymes but there are compounds that bind to the enzyme and they decrease enzymatic activity right so what occurs is that the speed of the reaction decreases because of these inhibitors and for example this is typically how drugs and toxins actually work if if you've seen you know movies with with snake poisons and things like that how how those poisons work is they enter the body and they inhibit certain enzymes and then the body cannot produce and facilitate a certain reaction fast enough so then organs begin to shut down and it causes system failures and this process could be reversible or irreversible it depends on the drug it depends on the toxin it depends on the molecule that inhibits these enzymes so here are the four common types of reversible inhibition that we will discuss and not to great detail but just to give an overview in case it comes up on the exam so the common types are competitive inhibition pure non-competitive inhibition mixed non-competitive inhibition and uncompetitive inhibition and we'll take a look at each one more closely and first let's begin with competitive inhibitors and what those are so structurally competitive inhibitors look and resemble normal substrates they look exactly the same they have the same kinds of shape they could differ a little bit in terms of their structural abilities and their functions however they are able to bind to inhibitors in exactly the same way in the exact same active site as the substrates that we need for the reaction now the binding of the inhibitor and the substrate to the enzyme is exclusive and that's the main point of competitive inhibitors they exclusively bind to the enzyme meaning that only the inhibitor or the substrate can bind to the enzyme so if the inhibitor binds to the enzyme then the reaction will not proceed but if the substrate binds to the enzyme then reaction will proceed so it is going to be a game of the concentration so the concentration of inhibitor versus the concentration of the substrate whichever molecule exists at a higher concentration will win and will be able to proceed and form products or if there's more inhibitors then more enzymes will be disabled and the reaction will not proceed so let's take a look at what these things look like in on an enzyme so here we have an illustration of an enzyme that's in yellow and the substrate right here it binds to the active site and the reaction proceeds reaction proceeds right however the same similar type of molecule that would be the inhibitor could also bind to the enzyme and if there's more if there is more inhibitor than the enzyme this will typically happen more often with the enzyme and then there is no reaction because the the inhibitor now occupies the active site and the substrate even if it just comes in if the substrate just comes in here and tries to bind it won't work it won't happen because that is taken up by the inhibitor all right next let's discuss the two types of non-competitive inhibition so there's the pure and there's the mix then we're going to decipher which one is which and how non-competitive inhibition works in general well basically the difference between competitive and non-competitive is that in non-competitive they're not competing for the active site so both the inhibitor and the substrate can bind simultaneously to the enzyme which means that they both have two different binding sites the substrate binds at the active site and the non-competitive inhibitor binds somewhere else now in pure non-competitive inhibition the inhibitor binds far away from the active site so it could bind further away from the active site and what it does is that it changes the enzyme conformation which then makes the enzyme less effective in in catalysis so it can convert less substrate and less amount of time or it can or it can just permanently stop the enzyme from working because it changed the enzyme conformation and remember enzymes are typically proteins and proteins work with structures so if structure is not there the protein will not work right so if it changes the enzyme conformation it changes its structure and typically the substrate would not be able to be converted to the product now in mixed non-competitive inhibition what we have is something very similar and it's just an inhibitor that binds close to the active site it binds right beside it typically right by the active site and what it does is it affects the affinity of the enzyme for the substrate so it may not change the conformation they may not stop the enzyme from working entirely however it changes the affinity so it the binding of the substrate is less because this affinity is changed by this mixed non-competitive inhibitor that binds close to the active site and the final type of enzyme inhibition that we're going to discuss is called uncompetitive inhibition and this type of inhibition occurs when the inhibitors bind to the enzyme substrate complex and what this means is that the enzyme has already binded with the substrate forming what is known as enzyme substrate complex and once this complex is formed only then the inhibitor binds and what occurs is no reaction because this inhibitor has bonded with the es complex the enzyme substrate complex so the reaction simply does not proceed now what it looks like in the diagram is that we have an enzyme we have the substrate so first this is number one the substrate binds to the enzyme and this binding occurs successfully in the active site however this uncompetitive inhibitor comes in and also binds to the enzyme and the substrate which makes no reaction it prevents the reaction from happening because now this this this enzyme is typically blocked and it just kind of stays in the enzyme without being turned into products all right and the final topic that we're going to discuss in terms of enzymes is going to be allosteric enzymes and and what they are what they do and how they work so allosteric enzymes they consist of multiple subunits and their binding of effector molecules that results in a conformational change con formational change that's the that's the final thing that occurs with allosteric enzymes and they they typically do not follow the the similar curves like michaelis-menten kinetics if you have done biochemistry before however what happens is they affect the enzyme kinetics meaning that they affect the rate of which enzymes work either positively being deactivators or negatively being the inhibitors so there's two types of effector molecules you could have activators or you could have inhibitors and each one can can have an effect on the enzyme and its and and its kinetics in terms of how fast it produces its products so allosteric enzymes they have an active site but they also have one or more regulatory sites and these regulatory sites is exactly where the effector molecules bind either its activators or inhibitors they bind to these regulatory sites whereas the substrate continues to bind to the active site as usual so let's take a look at this diagram here and what we have is that the metal here there's no effector that means the allosteric enzyme is going to precede its reaction in a normal rate as it typically would without any molecules affecting it but when the activator comes along it's affects enzyme kinetics which means it produces more substrate at a faster rate now if we have the negative effect which is the inhibitor binding to the regulatory site of the allosteric enzyme what we get is a slower rate of substrate production and the ultimate lowering of the number of substrates being produced as the final product so now let's take a look at an illustration of what um of of how this occurs in enzymes so here we have this molecule right here would be the effector this one right here is the substrate now obviously we know that this right here is the active site where the substrate binds but this little spot right there is going to be the regulatory site regulatory site and the regulatory site is where the effector binds whether it's positive activator or negative inhibitor the effector molecule will bind to the regulatory site it does not interfere with the active site now there's two things that could happen depending on whether it is an activator or an inhibitor so uh here we have the first one that occurs and that's it binds so the effector molecule binds to the regulatory site and what it does is it increases the affinity of of the substrate it increases the affinity of the enzyme for the substrate meaning that the substrate would bind to the enzyme more readily and that's because this is going to be an activator activation because this molecule is an activator it is an effector that activates the enzyme and the other scenario is going to be if this effector molecule it does affects it negatively and it would be an inhibitor so this is an inhibition and what happens in this scenario is that once the effector molecule binds to the regulatory site it changes the confirmation of the enzyme and it cannot bind to the substrate the substrate does not bind it it is out of there it cannot bind to the active site because the because of the change confirmation due to the binding of the inhibitor which is the effector molecule that binds to the allosteric enzyme so this takes us to the end of chemistry of living things we have completed that one and the next lecture we will talk about the cell as a basis of life and we will begin with the topic of cell theory and cell size [Music] you