Enzyme-Substrate Complex: Videos & Practice Problems

The enzyme-substrate complex (ES) forms when an enzyme binds to its substrate, acting as a transient intermediate in enzyme-catalyzed reactions. The interactions are primarily mediated by non-covalent forces, such as hydrogen and ionic bonds, which release binding energy (ΔG_b). This binding energy stabilizes the transition state, lowering the activation energy and accelerating the reaction rate. Understanding the distinction between intermediates and transition states is crucial, as intermediates appear at local energy minima, while transition states occur at local maxima in energy diagrams.

Enzyme-Substrate Complex

In this video, we're going to talk about the enzyme-substrate complex. So the enzyme-substrate complex is commonly abbreviated with the capital letters ES, and we're going to see that a lot moving forward throughout our course as well. The idea or the concept of an enzyme-substrate complex is actually really straightforward. It's literally just an intermediate that forms when the enzyme binds to its substrate. So pretty easy, right?

Recall from your previous chemistry courses that intermediates are transient molecules because they don't last very long before they react again. On an energy diagram, these intermediates appear at the local minimum energy points within a multistep reaction. It's really important not to confuse intermediates with transition states, which we covered in our last lesson video. Recall that transition states appear at the local maximum peak energy point. However, intermediates appear at the local minimum energy points. If you're having some difficulty visualizing the difference between transition states and intermediates, then hang on tight because in our next example video, we'll show you an example of what this looks like.

Now, down below here, what we're showing is a typical enzyme-catalyzed reaction where we have an enzyme, which is commonly abbreviated with the letter E, and a substrate, which is commonly abbreviated with the letter S. Then we know that the enzyme can form a complex with the substrate, known as the enzyme-substrate complex. Of course, the enzyme is able to convert the substrate into the product, which is commonly abbreviated with the letter P. Then, the enzyme is not consumed in the reaction, so it takes on the original form that it had before the reaction even started.

The next thing that I want you to know in this video is that the interactions that allow the enzyme to form a complex with the substrate are predominantly mediated by noncovalent forces, such as hydrogen bonds and ionic bonds, for example. But that's not to say that covalent bonds never form in the enzyme-substrate complex while catalysis is occurring, because they actually can occur, and we'll talk about that more when we talk about different types of enzyme catalysis later in our course. But for now, all I want you guys to know is that the majority of the interactions in the enzyme-substrate complex are noncovalent forces. These weak noncovalent forces that form between the enzyme and the substrate in the enzyme-substrate complex actually provide the driving force for enzyme catalysis. We'll be able to talk about this even more in our next lesson video. So I'm excited to see you guys in the next video. See you there.

Enzyme-Substrate Complex Example 1

Alright, so here's an example problem that's going to help us visualize the difference between transition states and intermediates. The example problem wants us to appropriately label the arrows in the reaction energy diagram below using the provided terms over here on the left. Notice that the energy diagram has free energy on the y-axis and the reaction coordinate or the time that passes as the reaction progresses on the x-axis. We know that every reaction begins with reactants and this arrow pointing to the beginning of our curve corresponds with the reactants, and the reactants of an enzyme-catalyzed reaction are known as substrates, which is option c. So we can go ahead and label this arrow right here with option c and cross it off our list.

We also know that every reaction ends with products, and this arrow here pointing to the end of our curve corresponds with the products, which is option a. So we can go ahead and label it with option a and cross it off our list. The remaining three arrows here correspond to either transition states or intermediates. Recall from our previous lesson video that intermediates appear at the local minimum energy points. Notice that this arrow is pointing to a local minimum energy point because it's showing up at the bottom of this valley. Because it's appearing at a local minimum energy point, this is an intermediate, which is option B, and we can label this arrow with option B and cross it off our list.

Both of these arrows up here are pointing to local maximum energy points because they are showing up at the top of a hill. Because they are showing up at local maximum energy points, we know that these are both transition states. We can put the double dagger symbol here to show that these are both transition states. Notice that the provided terms over here have 2 different transition states. We have a non-rate-limiting transition state, and then we have a rate-limiting transition state. Recall from your previous chemistry courses that rate limiting just means slow, and we already know that slow reactions have a large energy of activation. If we look at the first transition state here, the energy of activation is going to be the difference in energy from the substrate to the transition state, and so it'll be this energy barrier right here.

Now if we look at the energy of activation for the second transition state over here, it's going to be the difference in energy between its substrate, which would be the intermediate here, and this other transition state. So essentially, it's just going to be this little energy activation. And because this first transition state has a much larger energy of activation with this green bar here, in comparison to the second one, the larger one has a larger energy of activation, so it's going to be slower and it's going to be the rate-limiting transition state. So we can go ahead and label this one with option e, and we can cross that off, and the remaining one over here is gonna be option d, and we can cross that off. So that concludes this example problem, and I'll see you guys in our next video.

Enzyme-Substrate Complex

So in our last lesson video, we said that the interactions between the enzyme and the substrate in the enzyme-substrate complex predominantly consist of non-covalent forces. And when these non-covalent forces form between the enzyme and the substrate, they can be abbreviated with the symbol ΔG_B, and the quantity of binding energy is defined as the energy difference between the uncatalyzed and the catalyzed transition states. Binding energy is derived from the release of free energy when non-covalent interactions form in the enzyme-substrate complex.

Later in our course, we're going to talk about the exact factors that enzymes influence by utilizing the released binding energy to stabilize the transition state in the active site. Essentially, the main takeaway is that the way enzymes lower the energy of activation is by stabilizing the transition state. And really, that's the major takeaway from this video.

So, down below in our example image, notice on the far left, we have the same image that we have up above in our previous lesson video. We know that the enzyme and the substrate are able to interact with each other to form the enzyme-substrate complex. The enzyme is able to interact with the substrate in such a way to catalyze the reaction and make the products appear at a faster rate. The enzyme is released unaltered without being consumed by the reaction. It's in the exact state as it was before the reaction took place.

Over here on the right, what we have is an energy reaction diagram, and you can see that the uncatalyzed reaction is shown as a dotted line, and you can see that the transition state for the uncatalyzed reaction is incredibly high. Unlike our previous reaction energy diagrams, notice that the enzyme-catalyzed curve is actually showing the formation of the enzyme-substrate complex intermediate here. This is something that was not shown in our previous energy diagrams. In most energy diagrams, the enzyme-substrate complex is not going to be shown because the enzyme-substrate complex is an intermediate. It's a transient molecule that does not last very long. So we don't typically focus most of our attention on it. A lot of times, to simplify the enzyme-catalyzed curves, the enzyme-substrate complex is simply not shown. But here, we're showing the formation of the enzyme-substrate complex to reveal a more realistic depiction of an enzyme-catalyzed reaction.

Moving forward, what you'll probably see is that enzyme-substrate reactions are going to be shown without showing the enzyme-substrate complex. But here, what you'll notice is that there is a little bit of an energy of activation for the formation of the enzyme-substrate complex, but it's so small that it's not really an issue and it's able to form pretty readily. The enzyme-catalyzed reaction has a much lower energy of activation here for the transition state that corresponds with the formation of the products.

As we said earlier in our lesson, the quantity of binding energy is defined as the energy difference between the uncatalyzed and the catalyzed transition states. The uncatalyzed transition state is going to be the transition state that corresponds with the local maximum peak energy point for the uncatalyzed curve. The catalyzed transition state is going to correspond with the local maximum peak energy point for the enzyme-catalyzed curve. Essentially, the binding energy is defined as this green area that's shown here, that's the difference between these two transition states that correspond with each other. This binding energy is symbolized with ΔG_B. What you'll notice is that it's this binding energy that's utilized to stabilize the transition state and essentially lower the energy of the transition state. Once the transition state energy is lowered and stabilized, the reaction is able to proceed at a faster rate, and that's exactly how enzymes speed up chemical reactions, by utilizing binding energy to stabilize the transition state. Again, that's the major takeaway of this video.

We'll be able to utilize some of these concepts in our next video, so I'll see you guys there.

What can the binding energy (ΔG_B) of an enzyme catalyzed reaction tell us?

• A. The change in the rate/speed of the reaction.
• B. The change in the equilibrium constant (K_eq) of the reaction.
• C. The change in the reaction E_A between the catalyzed & uncatalyzed transition states.
• D. a & c.
• E. All options are true.

Answer: (D)

Which is the best definition of binding energy regarding enzyme catalysis?

• A. Energy absorbed by the enzyme upon its binding to the substrate.
• B. Energy released by interactions between the enzyme's active site & substrate.
• C. Energy released by the products of an enzyme.
• D. The difference in energy between the substrates & products.

Answer: (B)

Here’s what students ask on this topic:

What is an enzyme-substrate complex?

An enzyme-substrate complex (ES) forms when an enzyme binds to its substrate. This complex acts as a transient intermediate in enzyme-catalyzed reactions. The interactions within the complex are primarily mediated by non-covalent forces, such as hydrogen bonds and ionic bonds. These interactions release binding energy (ΔG_b), which stabilizes the transition state, lowers the activation energy, and accelerates the reaction rate. Understanding the distinction between intermediates and transition states is crucial, as intermediates appear at local energy minima, while transition states occur at local maxima in energy diagrams.

How do enzymes lower the activation energy of a reaction?

Enzymes lower the activation energy of a reaction by stabilizing the transition state. This stabilization is achieved through the release of binding energy (ΔG_b) when non-covalent interactions form between the enzyme and the substrate in the enzyme-substrate complex. The binding energy is the energy difference between the uncatalyzed and catalyzed transition states. By lowering the energy of the transition state, enzymes make it easier for the reaction to proceed, thereby increasing the reaction rate.

What types of interactions are involved in the formation of an enzyme-substrate complex?

The formation of an enzyme-substrate complex predominantly involves non-covalent interactions. These include hydrogen bonds, ionic bonds, van der Waals forces, and hydrophobic interactions. These weak interactions provide the driving force for enzyme catalysis by releasing binding energy (ΔG_b), which stabilizes the transition state and lowers the activation energy of the reaction. While covalent bonds can also form during catalysis, they are less common in the initial enzyme-substrate complex formation.

What is the difference between an intermediate and a transition state in an enzyme-catalyzed reaction?

In an enzyme-catalyzed reaction, intermediates and transition states are distinct entities. Intermediates are transient molecules that appear at local energy minima on an energy diagram and exist for a short duration before reacting further. In contrast, transition states occur at local energy maxima and represent the highest energy point along the reaction pathway. The enzyme-substrate complex is an example of an intermediate, while the transition state is the point at which the reaction is most unstable and has the highest energy.

Why is the enzyme-substrate complex often not shown in energy diagrams?

The enzyme-substrate complex is often not shown in energy diagrams because it is a transient intermediate that does not last very long. To simplify the representation of enzyme-catalyzed reactions, many energy diagrams omit the enzyme-substrate complex and focus on the overall energy changes, such as the activation energy and the transition state. However, including the enzyme-substrate complex can provide a more realistic depiction of the reaction mechanism, showing the intermediate steps involved in the catalysis.