In this video, we'll cover the higher level topics from C1.1 on enzymes and metabolism. Cells are going to produce a couple of different types of enzymes or potentially produce them. One type is called an extracellular enzyme, and this word extra means like outside, so like extraterrestrial life outside of our planet. And those are going to be produced on ribosomes that are on the rough ER, okay? So these ribosomes right here on the rough ER are going to produce those enzymes. And then they're going to travel by vesicles down here to the Golgi, and then they're going to be exported out of the cell. Okay, so great example here is our pancreatic cells. They produce digestive enzymes or even bacterial enzymes that can break down materials outside of the cell, like if there's saprotrophic bacteria, something like that. In contrast, we're going to have enzymes that are used within the cell, and that's what intracellular means, within the cell. So if it's an enzyme for use within the cell, that's going to be produced on one of these free-floating ribosomes in the cytoplasm. There's no need to be secreting them out of the cell. So a great example here, DNA polymerase. That's an enzyme that I'm going to need in the nucleus here during DNA replication. So no need to make that on one of the rough ER ribosomes. That will be made by one of the free-floating ribosomes. Now, no reaction, not even ones that are catalyzed by enzymes, are 100% efficient. Anytime I have to transform energy, I'm going to have energy that is lost as heat. Okay, so heat is given off as a byproduct of a lot of different cellular reactions. And we say that it's lost. It's not because we don't know where it is. It's because heat is not a usable form of energy. I'm not saying that we can't put it to a good purpose. We can, warm-blooded animals, use that heat that is lost to control their body temperature, okay? But what I'm saying when I'm saying that it's lost, that means we can't use it for other things. So for example, I cannot use the heat energy to power active transport or for locomotion. So it's not a usable form of energy in that way. When we think about cell respiration, taking glucose and oxygen, okay, and converting that into water, carbon dioxide, and ATP, the chemical energy that is in glucose, the goal there is to convert that into chemical energy in the form of ATP. But we're very inefficient at that process, okay? Because what we're forgetting about here is that in addition to the chemical energy in the form of ATP... that reaction also produces heat. In fact, we're about 90% inefficient. Most of the energy there is going to be lost as heat. So again, certain animals, like warm-blooded animals, can control their metabolic rate in order to control their body temperature. That's why we do things like shivering. We're making our muscles move to generate ATP. That's really just a way of pumping up the cell respiration process to produce heat. Okay, so we can do that. It's just not a usable form when we think about powering other cell processes. Theme C is all about interaction and interdependence, and there's no better example of that than our metabolic pathways. So when we think about all of the enzyme-catalyzed reactions that can happen in a cell, there are several different types of interactions they can have. You can either have a linear pathway. So linear pathways look like this, okay? And so an example here is glycolysis. or these pathways can be cyclical, okay? So like the Krebs cycle or the Calvin cycle, something like that. But what do they have in common? Well, they all include chains of enzymes and intermediate products. And so an example might look something like this. I start out with an original substrate, and the first enzyme in my chain creates an intermediate product, which is the substrate that enzyme two works on. And enzyme two is going to convert this product into this other intermediate, and then this intermediate is converted into the final product by a third enzyme. And so in order to get from the substrate to the final product, I may need a series of enzymes that produce a series of intermediates. Now, the whole goal of having enzymes in our metabolic reactions isn't just to speed them up, it's also to control them. And there are a few different ways that enzymes can be controlled or inhibited. So when we say this word inhibition, what we really mean is a way to stop that enzyme, whether that be temporary or permanent. One of the ways that we can do that is through something called non-competitive inhibition. Some people also call this allosteric inhibition and that's because this is when some kind of substance is going to bind to a site called an allosteric site. So we already know that on enzymes we have an active site which is where the substrate will bind. There's another spot on the enzyme called an allosteric site. This is someplace that is not the active site. It's away from the active site. And if an allosteric inhibitor binds there, what that does is it changes the shape of the active site, making it impossible for the substrate to bind. So instead of having an active site that is shaped in a way that the substrate can bind, we have now... change that shape, and this enzyme is now inhibited. It will not catalyze that reaction anymore. So this is how isoleucine works, and we'll come back to that example in just a little bit. Now allosteric inhibition was non-competitive because there was nothing competing for the active site. In competitive inhibition, we're going to have some kind of molecule with a similar shape competing for the active site with the real substrate. So that might be something like this, where I have a different molecule that has a similar shape to the substrate. competing for that active site. And if that happens, if this inhibitor, this competitive inhibitor, steals the active site from the substrate, then obviously the enzyme isn't going to be catalyzing that reaction anymore, or at least not for the moment. Great example here, this is how statins work. Statins are drugs that inhibit the enzyme that produces cholesterol, and they do that by kind of stealing this active site from the real substrate. It's a very similar molecule in shape. Now let's take a look at how these influence reaction rates differently. Without any kind of inhibitor, when I increase the substrate concentration, I increase the rate of reaction until I get to a maximum rate, okay? So that is with no inhibitor. if I add a competitive inhibitor, and I'll do that, let's say, in red, okay? If I add a competitive inhibitor, then in the very beginning, I'm going to have a slower rate because that inhibitor is competing with the active site or for the active site with the real substrate. So I'm going to have a slower rate. But as I increase the substrate concentration, that real substrate is going to eventually be able to out-compete the inhibitor if I increase the substrate concentration enough. So it becomes more likely that the real substrate will collide with the active site when I've increased the real substrate's concentration enough. So this can be reversed. In non-competitive inhibition, that's very different. So non-competitive inhibition, again, I'm never going to get up to that same maximum rate. And that is because that non-competitive or allosteric inhibitor has changed the shape of the active site. So even if you increase the real concentration or the concentration of the real substrate to really high levels, it doesn't matter because you've changed the shape of that enzyme's active site. So increasing the concentration won't have any kind of positive effect there on the reaction rate. So we've talked about competitive inhibition, non-competitive inhibition. Now we'll get to our final type of inhibition called feedback inhibition. Some people may also refer to this as end product inhibition. And to me, this is an easier way to remember this. Here's what happens. In an enzyme chain, okay, we're going to have an initial substrate turned into a final product. using a series of enzymes. So here I have three enzymes in my series. When the concentration of this final product is great enough, we don't want to keep producing it. We don't want to have an excess buildup of this final product. So what happens here in feedback inhibition or in product inhibition is that this end product becomes a non-competitive inhibitor of this very first enzyme in the chain. It binds to the allosteric site. So again, this final product becomes a non-competitive or allosteric inhibitor to that very first enzyme in the chain, and it shuts down this process, okay? So if this first process is inhibited, none of this substrate is even going to be made into the first intermediate. So I won't have any other part of this enzyme chain, okay? So it shuts down this entire chain. when this concentration drops low enough, then this process is reversed. So at low concentrations, this product will no longer be attached to this first enzyme. It'll kind of pop off, and this enzyme will no longer be inhibited, and the chain will start once again. And this is that example that we mentioned a few moments ago about threonine to isoleucine. So threonine is an amino acid that can act as a substrate, we need a series of enzymes in order to convert that to isoleucine. Well, great. That's awesome. If I need isoleucine. Once we have enough isoleucine, though, isoleucine becomes an inhibitor of the first enzyme in the chain, and then this entire pathway shuts down. One of the reasons why you'll see this referred to as feedback inhibition is because it refers to a negative feedback loop. Okay, it's a way of keeping things within a certain range of values so I don't get an excess buildup of product. Now in that threonine and isoleucine example, that is reversible. Okay, so once the product concentration drops enough, this pops off. It's no longer an inhibitor and everything starts working again. There are, however, some examples of some inhibitors that are not reversible, okay? So certain things like mercury or arsenic, those heavy metals, penicillin, certain chemical weapons, they bind to an amino acid somewhere in the chain, okay? So somewhere on one of the enzymes in the chain, and that non-competitive inhibition is permanent. So some things are permanent inhibitors. If that happens, then that permanent change will shut down that enzyme chain forever, and it can cause a really detrimental systemic damage to the organism. So that's exactly how penicillin works. It inhibits an enzyme in bacteria, and it kills the bacteria. Mercury, arsenic, chemical weapons, they are so devastating because they cause permanent change. to one of the enzymes in a chain. So it's not necessarily feedback inhibition. In fact, we'll even get rid of that here. It's just a type of non-competitive inhibition that is permanent. And again, one of the great examples to have in your mental toolbox here is the example of penicillin. Penicillin is an antibiotic, and it comes from the penicillium fungus. So this fungus produces a type of inhibitor that works on a bacterial enzyme called transpeptidase. Bacteria use this transpeptidase enzyme to build their cell walls. And so if you're taking a penicillin... a based antibiotic, what that's doing is it is permanently inhibiting the enzyme that bacteria use to build their cell walls, and it kills the bacteria. So it's really nice to get rid of a bacterial infection. We don't have to worry about that inhibitor damaging human cells because human cells don't have a cell wall. So we don't need this enzyme called transpeptidase. So it doesn't matter to us if that enzyme is permanently inhibited because we don't need it anyways. Neither do fungus. So this is a great example of a chemical adaptation that allows that fungus to out-compete neighboring bacteria for things like space and resources, and also a great example of how we've utilized one of those natural adaptations for human uses.