Hey guys, it's Metacosis Perfectionalis where medicine makes perfect sense. Thank you for watching my biochemistry playlist. In previous videos, we talked about enzyme kinetics.
We talked about Michaelis-Menten and Lynn Weaver-Burke plots. We talked about competitive inhibitors alone, non-competitive inhibitors alone, mixed inhibitors, and uncompetitive inhibitors. Today, let's compare among the four types of enzyme inhibitors and let's get started.
Please watch the videos in this playlist in order. There are four types of enzyme inhibitors as you know. Competitive, non-competitive, mixed and uncompetitive.
Enzymes facilitate the reaction. They are catalysts. They increase the speed. They lower the activation energy. They are not changed by the reaction.
They do not change the equilibrium position. They do not change the thermodynamics. They do not alter your delta G. Enzymes have two doors.
The front door and the back door. The front is the active site. The back door is the allosteric site.
The only inhibitor that binds the active site is competitive inhibitor. Every other inhibitor will bind to the allosteric site. Here is another difference. Competitive inhibitor is the only one that does not change your Vmax, which is the maximum rate of the reaction.
Every other inhibitor will lower your Vmax. Recall that Vmax is directly proportional to the number of enzymes available. and Km is inversely proportional to the affinity between the enzyme and the substrate.
Competitive inhibitors bind to the active site. Non-competitive inhibitors bind to the allosteric site. Mixed inhibitors, allosteric site.
Uncompetitive inhibitors, allosteric site. With competitive inhibitors, Km will climb because we crush the affinity. Can you overcome it? Yes, we can overcome it, and there is no change in Vmax.
With non-competitive inhibitors, KM does not change. VMAX goes down. Let's understand competitive inhibitors. Cody the capitalist. Imagine that we had a store that sells 10 cars per day to 10 different customers.
Then the competitive inhibitor, Cody the capitalist, open shop in front of the first one. What's going to happen to the attraction of customers to the old shop? It will decrease.
So the affinity will decrease and the KM will go up. But since... Cody the capitalist did not alter the total number of units sold. VMAX will stay the same. So with competitive inhibitors, Cody the capitalist, KM will climb by crushing the affinity.
You can overcome it. There is no change in VMAX. Next, non-competitive inhibitors, Nancy the Karen.
You were driving your car. You are the enzyme. Your car is the substrate.
Down the road. The speed limit was 15, but you went over the limit. Nancy started yelling at you. Quote, I'm gonna call the police on you. Close quote.
After hearing this, what's gonna happen to your speed? You will decrease your speed. VMAX goes down. But you still love your old piece of vintage Ford Model T car that needs to be cranked. So there is no change in affinity and no change in KM.
On McAllis-Menten graph, if I want to draw a competitive inhibitor, I will have to shift to the right, like this, but Vmax will not change. If I want to draw non-competitive inhibitor, my Vmax will have to decrease, like this. On the Linweaver-Bieber-Burke plot, competitive inhibitors will have to shift me to the right. Did they change the Vmax? No.
So I will intersect with the same point here, because that's Vmax. or 1 over Vmax to be specific. But if I want to draw non-competitive inhibitors, Vmax will have to decrease, which means 1 over Vmax will have to increase.
But Km should stay the same. And it should look like this. Be ultimous. Note that with competitive inhibitors, the old line and the new line intersected on the y-axis. But with non-competitive inhibitors, the old line and the new line intersected on the x.
axis. Here is competitive inhibitors and non-competitive inhibitors. Pause and review.
And you absolutely need to memorize this. Competitive inhibitor is Cody the Capitalist, active site. Affinity decreased because less customers went to the old store, which means KM went up.
However, the total number of units sold did not change. VMAX will stay the same. Nancy the Karen delves through the back door.
When she yelled at you, your speed decreased, but you still love your car in the same manner. Mixed inhibitors. Sometimes they bind to the enzyme alone, in which case affinity decreases because you're less likely to bind to the enzyme as a substrate. MKM will go up. Or mixed inhibitors might bind.
to the enzyme substrate complex, all of them together, after they have hugged each other, which means the love bond between them is high and Km is low. So mixed inhibitor can bind this or this with different affinity for each, which is what distinguishes mixed inhibitors from non-competitive inhibitors. Mixed inhibitors, like most inhibitors, bind the allosteric site, and like most inhibitors, Vmax will decrease. If I draw the old line and the new line, I drew two lines because it could be this one or this one. Note that the old line and the new line intersected here or here.
Whether you intersect here or here, neither point is on either axis. So with mixed inhibitors, we bind to the allosteric site, Km might increase and the affinity will go down, or Km will decrease because the affinity went up, Vmax will always go down. Let's add the uncompetitive inhibitor.
Still binds to the allosteric site. Km goes down because the affinity goes up. Vmax goes down. So the only inhibitor that decreases both the Km and the Vmax is the uncompetitive inhibitor. So here is a cool way to remember it.
Competitive inhibitors are unique. They are the only type of inhibitors that bind to the active site. Every other inhibitor is going to bind to the allosteric site.
Competitive inhibitors are unique. They are the only inhibitors that do not change your Vmax. Every other inhibitor will lower your Vmax. Uncompetitive inhibitors. They only bind the enzyme substrate complex after they have hugged each other.
After they have hugged each other? Yeah, and will lock them in place by preventing their detachment. All right, we have already hugged each other, and we will never detach, so the hugging is very strong.
Affinity is high, Km is down. This enzyme is not available to function anymore with any other substrate, so Vmax will drop. Vmax will drop, so 1 over Vmax will go up, and Km will decrease, so we will shift to the left.
Again, uncompetitive inhibitor is the only one that decreases both the Km and the Vmax. I decrease the Vmax, I decrease the Km, so the two lines are parallel. Pause and review.
Let's add something else. What's the relationship between the old line, the control line, and after adding the new inhibitor? Let's see. With competitive inhibitors, both will intersect at the Y-axis.
With non-competitive inhibitors, both will intersect at the X-axis. The way I remember it is that I imagine that Karen is threatening to slit my throat, metaphorically speaking, by doing this horizontal across-the-neck motion. Horizontal axis is the x-axis. My students always recall my crazy mnemonics and they start laughing hysterically in the middle of the exam. Next, with mixed inhibitors, both lines will intersect at a point that's neither on the x-axis nor the y-axis.
With uncompetitive inhibitors, both lines are parallel to one another. Let's draw a competitive inhibitor. Are you ready?
Sure! Cody the capitalist decreased the affinity which means KM goes up, but did not change the number of units sold, so the Vmax did not change. You just join these two lines together.
See that the old and the new line intersected on the vertical axis. Next, non-competitive inhibitors, Nancy the Karen. When she yelled at me, I decreased my speed, which means 1 over Vmax will go up. And then, KM did not change.
You just match these two points together. Note that the old line and the new line intersect on the horizontal axis, as Karen threatens me horizontally. With mixed inhibitors, Vmax will always decrease, so 1 over Vmax will always increase. And then, sometimes Km goes up, in which case we draw a line like this, and sometimes Km will decrease, in which case we draw a line like this. The old line.
and the new line will intersect at a point that's neither on the x-axis nor on the y-axis. Last, uncompetitive inhibitors, the only inhibitor that decreases both the Km and the Vmax. Let me decrease the Vmax, let me decrease the Km, and voila, both lines are parallel. Oh, medicosis, biochemistry is so hard and nothing makes sense. Oh, shut up.
Medicine makes so much sense once you understand what the flip you're talking about. If you want to be a good student, bring a piece of paper and draw everything here from scratch without looking. If you like this video, if you love math and want more graphs, check out my general pharmacology course. Tons of pharmacokinetics and pharmacodynamics.
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