Allosteric Effectors - Online Tutor, Practice Problems & Exam Prep

Allosteric effectors are regulatory molecules that bind to allosteric sites on enzymes, influencing their activity. They are categorized as heterotrophic effectors, which affect different molecules, and homotrophic effectors, where the substrate itself acts as the effector. Additionally, effectors can be activators, stabilizing the R state and shifting the sigmoidal curve left, or inhibitors, stabilizing the T state and shifting the curve right. For example, ATP acts as an activator for aspartate transcarbamylase (ATCase), while CTP serves as an inhibitor, demonstrating the dynamic regulation of enzyme kinetics.

Allosteric Effectors

In this video, we're going to begin our lesson on allosteric effectors. So at this point in our course, we already have somewhat of an idea that allosteric effectors are just regulatory molecules that bind to allosteric sites on an allosteric enzyme in order to regulate the enzyme's activity or initial reaction velocity, \( v_0 \). Now, it turns out that these allosteric effectors can really be grouped broadly into 2 separate categories. And these two categories are heterotropic effectors as well as homotropic effectors. And so the prefix hetero means different, whereas the prefix homo means the same. And so heterotropic allosteric effectors are just molecules that affect an allosteric enzyme's activity on a different molecule. Again, since hetero means different. And then, of course, homotropic allosteric effectors are just going to be molecules that affect an allosteric enzyme's activity on that same exact molecule since, again, homo means the same. And so in other words, when it comes to homotropic effectors, it's pretty much saying that the substrate itself is going to act as the allosteric effector. And so all of this can be pretty confusing, so let's take a look at our example down below of heterotropic versus homotropic effectors to clear some of this up. And so we're going to start off with the left-hand side of our image over here and notice that this red structure right here represents our allosteric enzyme, which is catalyzing this reaction right here, converting the substrate into the product over here. And notice that this yellow molecule right here is acting as an allosteric effector to regulate the allosteric enzyme's activity on this reaction. And so, notice that it's labeled specifically as a heterotropic effector. And so the reason that this yellow molecule is a heterotropic effector and not a homotropic effector is because this yellow molecule itself is acting as an allosteric effector to affect the allosteric enzyme's activity on a different molecule, which is the substrate itself. And so, essentially what we're saying is that because the substrate is structurally a different molecule than the allosteric effector, that is what makes the allosteric effector a heterotropic effector. It's because these 2 molecules are different from each other, and again, hetero means different. Now, if we compare this to the right-hand side of our image over here, notice again we have the allosteric enzyme here catalyzing the same exact reaction. And this time, notice that the substrate itself is really acting as the allosteric effector, to affect the allosteric enzyme's activity on the same exact molecule. And so this is what makes this the homotropic effector. And again, the reason that it's a homotropic effector is because the substrate itself is what's acting as the allosteric effector. And so, now that we've introduced heterotropic and homotropic effectors, in our next lesson video we're going to talk about yet another way to categorize allosteric effectors. So I'll see you guys in that video.

Allosteric Effectors

So in addition to grouping allosteric effectors as either heterotropic or homotropic, allosteric effectors can also be grouped in 2 other ways based on their results, either as activators or as inhibitors. Now, activators are commonly represented with a positive sign, whereas inhibitors are commonly represented with a negative sign. Now, activators are going to be allosteric effectors that specifically stabilize the R-state conformation of the allosteric enzyme. And, of course, stabilizing the R-state is going to increase the concentration of R-state and therefore, decrease the allosteric constant L₀ and that's because L₀ recall is just the ratio of the T state to the R state and again, increasing the concentration of our state is going to decrease this higher ratio as we mentioned here. Now, these allosteric effectors that act as activators, as we'll see down below in our image, are going to cause a shift in the sigmoidal curve to the left. Now, inhibitors on the other hand are going to be allosteric activators that stabilize the T state conformation of the allosteric enzyme. And and, of course, stabilizing the T state is going to increase the concentration of the T state even further, and that's going to increase the allosteric constant L₀, which is again this ratio right here of the T states over the R states and so increasing the concentration of T will increase this ratio and inhibitors on the other hand are going to cause a shift in the sigmoidal curve to the right, as we'll see down below in our image.

So in our example down below, we're going to look at the heterotrophic effects of ATP and CTP on the allosteric enzyme aspartate transcarbamylase or ATCase for short. And so notice down below in this blue box right here, what we have is the reaction that's catalyzed by the enzyme ATCase. And so ATCase converts carbamoyl phosphate and L-aspartate into carbamoyl aspartate and inorganic phosphate. Essentially, just swapping the pink here with the brown. And so notice that in green with this positive sign here, the molecule ATP is acting as an allosteric activator for the enzyme ATCase. And then, of course, in blue with the negative sign here, the molecule CTP is acting as an allosteric inhibitor for the enzyme ATCase.

And so taking a look at the enzyme kinetics plot down below, notice that we have these 3 different curves. This black curve right here represents the enzyme catalyzed reaction up above in the absence of any allosteric effectors. The green curve represents, again, the same exact enzyme catalyzed reaction up above, except in the presence of an activator. And of course, we can see that ATP is the molecule acting as the allosteric activator for the enzyme ATCase. Now, here in blue, what we have is the same exact enzyme catalyzed reaction up above, except this time in the presence of an allosteric inhibitor. And of course, we know that CTP is the molecule acting as the allosteric inhibitor for the enzyme ATCase.

And so comparing this with what we set up above, notice that activators are going to stabilize the R-state and cause a shift in the sigmoidal curve to the left. And so notice that in the presence of absence of inhibitor. And also notice that we said that inhibitors are going to stabilize the T state and cause a shift in the sigmoidal curve to the right. And so looking at this blue curve down below, notice that in comparison to the black curve, it is indeed shifted to the right. And so, what helps me remember this shift to the left and the shift to the right is actually a completely different mindset. And so, if you pick any substrate concentration that you want, any particular substrate concentration, and you compare the initial reaction velocities of all three of the curves, we know that, activators are going to increase the initial reaction velocity with respect to the green curve, and so we expect activators to have a higher initial reaction velocity. So we can imagine plotting a point here. And with inhibitors, of course, with respect to the absence of any effectors, we expect inhibitors to decrease the initial reaction velocity, so we would have a point down here. And so if you repeat this process many, many, many times, then it becomes very clear that in the presence of an inhibitor, of course, it's going to be shifted to the right. And so a decreased initial reaction velocity corresponds with a shift of the curve to the right. And, of course, an increase in the initial reaction velocity is going to correspond with a shift of the sigmoidal curve to the left, as we see with the green curve. And so notice that here, in this image, that none of these effectors are affecting the v_max of the enzyme. They're all going up to this v_max horizontal, asymptote here. However, there are some scenarios where effectors can affect the v_max and so, of course, if an activator affects the v_max, it's going to increase the v_max. Whereas, if an inhibitor affects the v_max, it's of course going to decrease the v_max. And so, this here concludes our introduction to allosteric activators and inhibitors, and we'll be able to get some practice utilizing these concepts in our next couple of practice videos. So I'll see you guys there.

L-arginine is capable of binding to and activating N-acetylglutamate synthase. Since L-arginine is neither a substrate nor a product of this enzyme, how would this effector be classified?

• A. (-) homotropic effector.
• B. (+) heterotropic effector.
• C. (-) heterotropic effector.
• D. (+) homotropic effector.

Considering that O₂ triggers hemoglobin to switch from its low affinity (T) state to its high affinity (R) state to bind more O₂, what kind of allosteric effector is O ₂ relative to hemoglobin?

• A. Heterotropic; activator.
• B. Homotropic; inhibitor.
• C. Heterotropic; inhibitor.
• D. Homotropic; activator.

Which of the following statements about allosteric control of enzymatic activity is false?

• A. Allosteric effectors give rise to sigmoidal V₀ vs. [S] kinetic plots.
• B. Allosteric proteins are generally composed of several subunits.
• C. An allosteric effector may either inhibit or activate an enzyme.
• D. Binding of the allosteric effector to the enzyme changes the conformation of the enzyme.
• E. Heterotropic allosteric effectors compete with the substrate for binding sites on the enzyme.

Here’s what students ask on this topic:

What are allosteric effectors and how do they regulate enzyme activity?

Allosteric effectors are regulatory molecules that bind to specific sites on enzymes, known as allosteric sites, distinct from the active site. These effectors influence the enzyme's activity by inducing conformational changes. They can be categorized into two main types: heterotrophic effectors, which affect the enzyme's activity on a different molecule, and homotrophic effectors, where the substrate itself acts as the effector. Additionally, allosteric effectors can function as activators, stabilizing the R state and increasing enzyme activity, or as inhibitors, stabilizing the T state and decreasing enzyme activity. This regulation is crucial for maintaining metabolic balance within cells.

What is the difference between heterotrophic and homotrophic allosteric effectors?

Heterotrophic allosteric effectors are molecules that bind to an allosteric site on an enzyme and affect the enzyme's activity on a different molecule, typically the substrate. In contrast, homotrophic allosteric effectors are the substrate molecules themselves that bind to the allosteric site and regulate the enzyme's activity on the same substrate. Essentially, heterotrophic effectors involve different molecules (hetero means different), while homotrophic effectors involve the same molecule (homo means same).

How do allosteric activators and inhibitors affect the sigmoidal curve of enzyme kinetics?

Allosteric activators and inhibitors influence the sigmoidal curve of enzyme kinetics differently. Activators stabilize the R state of the enzyme, increasing its activity and causing a leftward shift in the sigmoidal curve. This shift indicates a higher initial reaction velocity at lower substrate concentrations. In contrast, inhibitors stabilize the T state, decreasing enzyme activity and causing a rightward shift in the sigmoidal curve, indicating a lower initial reaction velocity. These shifts reflect changes in the enzyme's affinity for the substrate and its overall catalytic efficiency.

Can allosteric effectors affect the V_max of an enzyme-catalyzed reaction?

Yes, allosteric effectors can affect the V_max of an enzyme-catalyzed reaction, although this is not always the case. Activators can increase the V_max by enhancing the enzyme's catalytic efficiency, while inhibitors can decrease the V_max by reducing the enzyme's activity. However, in many scenarios, allosteric effectors primarily affect the enzyme's affinity for the substrate (K_m) without altering the V_max. The specific impact on V_max depends on the nature of the effector and the enzyme involved.

What role do ATP and CTP play as allosteric effectors in the regulation of aspartate transcarbamylase (ATCase)?

ATP and CTP serve as allosteric effectors in the regulation of aspartate transcarbamylase (ATCase). ATP acts as an allosteric activator, stabilizing the R state of ATCase and increasing its catalytic activity, which shifts the sigmoidal curve to the left. This enhances the enzyme's ability to convert carbamoyl phosphate and L-aspartate into carbamoyl aspartate and inorganic phosphate. Conversely, CTP acts as an allosteric inhibitor, stabilizing the T state of ATCase and decreasing its activity, shifting the sigmoidal curve to the right. This dynamic regulation by ATP and CTP helps balance the synthesis of nucleotides in the cell.