all right Welcome to our third and final video for chapter six in this video we're going to talk more about enzyme so how do enzymes lower the activation energy for an endergonic or extragonic reaction they help the substrate reach the transition state in one of several ways so either it can position two or more substrates so they align perfectly for the reaction to happen they can provide a optimal environment for the reaction to happen remember there are specific amino acids in the active site and these might for example be acidic or water loving or polar so that the substrates will be more likely to bind and align together for the reaction to happen sometimes people say enzymes are kind of like matchmakers for couples they speed up the likelihood or the chance that the couples will get together the enzyme might even contort or stress the substrate so it's less stable and more likely to react or it temporarily reacts with the substrate directly the active site binds or reacts with a substrate it might chemically change it or temporarily change it so that it's more likely to react but remember I I keep saying this because it's very important at the end of the reaction the enzyme becomes available again to catalyze the next reaction so the enzyme is unchanged at the end of the reaction remember since most enzymes are proteins that three-dimensional shape is dependent upon the amino acid sequence that primary structure of the polypeptide so the amino acids AA stands for amino acids these amino acids in the active site are really important in order for the substrate to bind to the active site and I mentioned earlier that temperature is important because if you lower or raise the temperature too much the three-dimensional shape of the protein might change especially if it gets too warm the protein might denature or lose its three-dimensional shape and if you have a different pH then what can happen is different pH values can actually change the let me find one over here I don't have any good ones it can change the state of the active site it might get rid of the negative charge or add a positive charge to the active site which can minimize that bonding strength between the substrate and enzyme I won't click on the video here because it takes about five minutes or so but in our PDF slides on canvas if you go to the slides and you cut and paste the link here into your browser it has a nice short video about how enzymes work and you can see the three-dimensional shape of the active site and how it reacts with the substrate so how do we regulate enzymes if their purpose is to speed up reactions because maybe I don't want the reaction to be happening at some moment in time for example so here our book gives us an example of the digestive cells and really the enzymes in our stomach work harder after a meal than when we sleep how do we make sure we're not actively digesting if there's no food to digest luckily we can regulate our enzymes through many ways one example is through changing the temperature or pH of the environment and the stomach I know the stomach is very acidic pH of 2 or less than two luckily the digestive enzymes in the stomach work at that optimal pH so if I had something like an ulcer and those digestive enzymes leaked out of the stomach and into my blood my blood has a pH of about 7.4 those PH2 enzymes that work really well in my stomach luckily will not work in my blood so I don't have to worry about those enzymes chopping up the proteins I need to survive and I can also make molecules that promote or inhibit the enzyme function and we'll talk about that in a bit many enzymes also need coenzymes or cofactors in order to function properly luckily enzymes are also compartmentalized they're localized or located in specific places based on their function for example those digestive enzymes in my stomach or the digestive enzymes in my lysosomes they're nicely packaged so they can only work in that region in that location another way we can regulate enzymes is through inhibition and there are two types of Inhibitors we can use competitive Inhibitors and non-competitive inhibitors competitive Inhibitors are what they sound like they compete with a substrate for the active site so if I look at my picture on the right here's the substrate and it normally binds here at the active site but if I have a competitive inhibitor that looks very similar to the substrate and can bind to the same site I can prevent the substrate from binding and the reaction from happening it's a lot like playing musical chairs where there is one chair but maybe two people competing for that same chair only one person gets to sit in that chair the other type of inhibitor we have are non-competitive inhibitors these will not look like the substrate here's my non-competitive inhibitor you can see it does not look like the substrate so it doesn't bind to the active site it binds at a different site usually called the allosteric site and what it does is it prevents the reaction from happening either by changing the shape of the active site so the substrate can no longer bind or in this case I can see the substrate can still bind but it changes the shape of the enzyme in this case the enzyme can no longer close for both sites to bind because this is taking up space right here it changes the shape ultimately of the enzyme so it no longer can go through the usual reaction resulting in no reaction happening so how do Inhibitors change reaction rates if I look at this graph on the y-axis I have the rate of the reaction on the x-axis I have the substrate concentration without Inhibitors I can see the normal rate of the reaction catalyzed enzyme increases and gets saturated over time when all the enzymes are used up there's a maximum reaction rate and that we learned about before is saturation so all of the enzymes are in use at the moment if I have a competitive competitive inhibitor it looks like I can also eventually reach that saturation point my highest reaction rate but it takes more time and the reason for that is because the competitive inhibitor is binding to some of those active sites and I can overcome this by increasing the substrate concentration this is actually what happens when we have individuals with carbon monoxide poisoning that we can still save it turns out that in our red blood cells we have these proteins called hemoglobin proteins that bind to oxygen but carbon monoxide can bind to the same site that oxygen usually binds to so what happens is to get rid of carbon monoxide poisoning you can put a person into a room under high pressure 100 oxygen to overcome to out-compete that competitive inhibitor in the last example over here non-competitive inhibition I can see that I never reach that saturation point because even if I increase the substrate concentration the non-competitive inhibitor is not binding to the active site it's binding to the allosteric site and changing the shape of the enzyme so it no longer functions properly so you cannot out compete a non-competitive inhibitor so I mentioned non-competitive Inhibitors bind to a different site called the allosteric site to cause allosteric inhibition so these are also known as allosteric Inhibitors and I have an example shown up here the red one is an example of an allosteric inhibitor because it's not binding to the active site that's the active site instead it's binding to a different site called the allosteric site and in the case of this four subunit enzyme it looks like the allosteric inhibitor stabilizes the inactive form where the active site is closed so the substrate cannot bind and the reaction does not happen but we also have allosteric activators these are proteins or molecules that will bind to the allosteric site as well but they optimize the active site so the substrate can bind so allosteric activators will promote the reaction and allow the infinity the likelihood for the substrate to bind to the active site to increase whereas allosteric Inhibitors will change or close the active site so you reduce or even prevent The Binding of the substrate to the active site if we think of some of our pharmaceutical drugs and how they're developed many of them work by inhibiting enzymes along metabolic pathways so one example are a group of drugs called statins statins statins their purpose is really to lower cholesterol levels in the blood and one enzyme that's really important here is HMG COA reductase this is an enzyme that produces cholesterol from lipids so if we can inhibit this enzyme we can actually reduce the amount of cholesterol produced and lower the cholesterol levels in the blood and in this case this is actually a type of competitive inhibition so statins work by blocking the active site of hmg-coa reductase so you don't have to memorize this for the test or anything but here's an example of that enzyme HMG COA reductase that produces cholesterol from our lipids and here's another way to regulate enzyme function is through the presence or availability of cofactors and coenzymes remember I mentioned earlier that most enzymes will require some kind of cofactor or coenzyme to to function properly and the difference between cofactors and coenzymes are whether they're organic or not cofactors are usually inorganic ions like these different Metals here one example we'll see later is DNA polymerase an enzyme that produces DNA requires zinc as a cofactor in order to work properly coenzymes are similar but these are organic molecules usually some kind of metal bonded to a carbon-containing organic molecule and these include ATP nadh and different vitamins we get from our diet so here are some examples of vitamins that function as coenzymes to allow our enzymes to work properly maybe in other classes or in books you've read in the past you've heard of scurvy which people used to get when they were on ships traveling across the ocean for long periods of time so they would have to bring things like limes or oranges to make sure they prevent scurvy and this is because many of the enzymes that build our connective tissue collagen so under the skin require vitamin C as a coenzyme to function properly so when people didn't get enough vitamin C from foods and fruits like these oranges or lemons or limes then they would not have enough of the cofactor for the enzyme to function so they wouldn't have enough collagen and you would see these symptoms you would see lesions on the skin that was probably the most common because it's most visible and other symptoms like irritability joint pain scaly skin Etc and in addition to competitive and non-competitive inhibition we also have a very important type of inhibition called feedback inhibition and if I think about my metabolic pathways that are happening inside of the cell there is no like power or on and off switch inside of our cells so how do our cells know when to start making some kind of molecule and when to stop making it when we have too much of it luckily there is some kind of self feedback we call feedback inhibition in our metabolic reactions and this is a really important way that cells self-regulate how much of a molecule they're making so let's see how this works here is my enzyme and it looks like there's an active site that the substrate usually binds in this case it's an amino acid called threonine threading binds to the active site produces some kind of intermediate sends it to the next enzyme Etc it produces a bunch of intermediates eventually you get your product that you want from this metabolic pathway called isoleucine so what happens when I have way too much isolucine and I'm like okay stop making this because I'm burning a bunch of energy powering these reactions and I already have way too much isoleucine luckily we have feedback inhibition where the end product of the reaction of this long metabolic pathway can act as an allosteric inhibitor it binds to the allosteric site which results in a closure remember that change in the active site so now that it's closed the substrate threonine can no longer bind to this active site and over time you'll see that these reactions stop you no longer make isoleucine and the levels of isoleucine will drop down to normal so this is really neat because how it self-regulates is once you have not enough or you run out of isoleucine it'll fall off you won't have enough to bind to the allosteric site the active site will open up again and you can make more of these intermediates and more isoleucine in the reaction again so feedback inhibition usually involves an inhibitor that's an allosteric inhibitor which also happens to be one of the end products or if if not the end product the final end product of the pathway so we're going to see that this is a really nice method for solves to self-regulate the production rate of some kind of product where too much of the product acts as an allosteric inhibitor and we'll see in chapter 7 that ATP itself can be an allosteric inhibitor for some of the enzymes involved in a process known as cellular respiration the focus of our next chapter all right that takes us to the end of chapter six in the next chapter chapter 7 we're going to be talking about the topic of cellular respiration how we break down