Catalysis - Online Tutor, Practice Problems & Exam Prep

Enzymes lower activation energy through various mechanisms, including acid-base catalysis, electrostatic catalysis, metal ion catalysis, and covalent catalysis. General acid-base catalysis involves proton transfer mediated by the enzyme, enhancing reaction rates. Specific acid-base catalysis relies on the solvent, typically water, as the proton source. The stability of charged intermediates is crucial, as their high free energy can hinder product formation. Understanding these mechanisms is essential for grasping enzyme kinetics and reaction specificity in biochemical processes.

Catalysis

In this video, we're going to begin our discussion on the different types of enzyme catalysis. So recall from our previous lesson videos that enzymes can actually lower the energy of activation required for a reaction in several different ways, including lowering the entropy of the system by bringing substrates closer together so that they can react faster, properly orienting the substrate so that their functional groups are also properly oriented and they can react easier, making conformations easier, and desolvating a substrate so that it can achieve transition state confirmations easier, and desolvating a substrate so that the hydration shells do not interfere and slow down the reaction. And again, these are all different ways that enzymes can lower the energy of activation that we already covered in our previous lesson videos. And so, between all of these different ways, we know that there is still a common theme to stabilize the transition state.

Now what we haven't yet talked about are the different types of enzyme catalysis reaction mechanisms that enzymes use. And so, what are some of those different types of enzyme catalysis mechanisms? Well, it turns out there are 4 mechanisms that enzymes primarily use for catalysis, and so the first is acid-base catalysis. The second is electrostatic catalysis. The third is metal ion catalysis. And the fourth is covalent catalysis. And so, moving forward in our course, we're going to talk about each of these different types of enzyme catalysis reaction mechanisms in their own separate videos. But in our next lesson video, we'll talk about the very first enzyme catalysis mechanism, which is acid-base catalysis. And so, I'll see you guys in that lesson video.

Catalysis

So in our last lesson video, we said that there are 4 main types of enzyme catalysis. In this lesson video, we're going to talk about our very first one, which is general acid-base catalysis. Acid-base catalysis is when either an acid or a base catalyzes a reaction via a proton transfer, or an H+ transfer, since we already know that acids and bases are all about either donating or accepting protons. Unstable charged intermediate molecules that form during a reaction can actually be stabilized with proton transfers, which is exactly why acid-base catalysis can be critical to some reactions.

Let's take a look at our image below in our example to clear up some of this. Notice that what we have here is a reaction in this box, and below, we have the free energy diagram for the same exact reaction. This reaction is a 2-step reaction shown by these two reaction arrows. In the first step of our reaction, the electron density on this blue oxygen is attacking our carbonyl group, and the electron density in the double bond of this carbonyl group is shifting up onto this red oxygen. Ultimately, this leads to the formation of this charged intermediate molecule here, where this red oxygen has a negative charge. Recall that sometimes these charged intermediate molecules can be unstable. It turns out that’s exactly the case with our charged intermediate molecule here; it's unstable. We can tell from our free energy diagram below, where its free energy is actually higher than the free energy of either the reactants or the product, making our charged intermediate unstable.

Notice that the rate of the forward reaction, or the energy of activation for the forward reaction to convert the intermediate into the final product, is significantly larger than the energy of activation required for the reverse reaction to convert the intermediate back into the reactants. A smaller energy of activation means that the reaction occurs faster. This means that the backwards reaction occurs much faster than the forward reaction because of the larger energy of activation. When this intermediate forms, the tendency is for it to break down back into the reactants, rather than to go forward and be converted into the final product. We can actually get a more substantial rate of formation for this product if we decrease the energy of activation for this second step of our reaction.

The second step of our reaction, indicated by this second arrow, is just a proton transfer or an H+ transfer. Essentially, a proton is being transferred to this red oxygen to protonate it and stabilize our final product. As we can see below, our final product is stabilized because it has such low free energy.

This second step, this proton transfer, can be catalyzed by two main types of acid-base catalysis. The first main type is specific acid-base catalysis. With specific acid-base catalysis, only one specific acid or base can serve as the proton transfer source, and that one specific acid or base is the solvent. Only the solvent can serve as the proton transfer source with specific acid-base catalysis; that’s why it’s so specific. Recall that in biological systems, the solvent is water. With specific acid-base catalysis, water will always serve as the proton transfer source. However, this process can sometimes be too slow.

The second main type of acid-base catalysis we want to focus on in this video is general acid-base catalysis. General acid-base catalysis is quite general because it doesn’t require a specific acid or base; any acid or base can serve as the proton transfer source. The enzyme’s active site will mediate the proton transfer, speeding up the reaction and lowering the energy of activation. We can see this by the green curve in our energy diagram. The product is formed at a more substantial rate due to the lowered energy of activation.

If the solvent serves as the proton transfer source, it is specific acid-base catalysis because the water can autoionize and form H3O⁺ or the hydronium ion, which can serve as the proton transfer source. But if the enzyme mediates the proton transfer, it is general acid-base catalysis, and it is marked with green in our diagram below. This concludes our lesson on the difference between specific and general acid-base catalysis, and we'll be able to apply these concepts in our practice problems. See you there!

Which of the following could not clearly be a contributor to general acid-base catalysis (circle all that apply)?

• A. Lysine.
• B. Glutamic acid.
• C. Water.
• D. Tyrosine.
• E. Phenylalanine.

The catalytic mechanism below is an example of:

• A. General acid catalysis.
• B. Specific acid catalysis.
• C. General base catalysis.
• D. Specific base catalysis.

Which of the following best applies to general acid-base catalysis?

• A. A proton is transferred between the enzyme and substrate.
• B. Uses nucleophilic functional groups.
• C. May take part in interactions involving Fe²⁺.
• D. Catalyst retains its original form after reaction occurs.
• E. Other than losing/gaining a H⁺, the catalyst retains its original form.
• F. a & d.
• G. a & e.

Here’s what students ask on this topic:

What are the different types of enzyme catalysis mechanisms?

Enzymes utilize four primary types of catalysis mechanisms to lower the activation energy of reactions: acid-base catalysis, electrostatic catalysis, metal ion catalysis, and covalent catalysis. Acid-base catalysis involves proton transfer to stabilize charged intermediates. Electrostatic catalysis uses charged residues in the enzyme to stabilize transition states. Metal ion catalysis involves metal ions that can stabilize negative charges or participate in redox reactions. Covalent catalysis forms a transient covalent bond between the enzyme and the substrate, facilitating the reaction. Understanding these mechanisms is crucial for studying enzyme kinetics and reaction specificity in biochemical processes.

How does acid-base catalysis work in enzyme reactions?

Acid-base catalysis in enzyme reactions involves the transfer of protons (H⁺) to stabilize charged intermediates that form during the reaction. This can occur via specific acid-base catalysis, where the solvent (usually water) acts as the proton donor or acceptor, or via general acid-base catalysis, where the enzyme itself mediates the proton transfer. By stabilizing these intermediates, the enzyme lowers the activation energy, making the reaction proceed faster. This mechanism is essential for many biochemical reactions, including those in metabolic pathways.

What is the difference between specific and general acid-base catalysis?

Specific acid-base catalysis involves the solvent, typically water, as the proton donor or acceptor. In contrast, general acid-base catalysis involves the enzyme's active site mediating the proton transfer, allowing any acid or base to serve as the proton source. Specific acid-base catalysis is often slower because it relies solely on the solvent, while general acid-base catalysis is faster due to the enzyme's involvement, which lowers the activation energy and speeds up the reaction.

Why is the stability of charged intermediates important in enzyme catalysis?

The stability of charged intermediates is crucial in enzyme catalysis because unstable intermediates with high free energy can hinder the formation of the final product. If the intermediate is too unstable, the reaction may revert to the reactants rather than proceed to the product. Enzymes stabilize these intermediates through various mechanisms, such as proton transfer in acid-base catalysis, to lower the activation energy and ensure a higher rate of product formation.

How do enzymes lower the activation energy of biochemical reactions?

Enzymes lower the activation energy of biochemical reactions through several mechanisms: bringing substrates closer together to increase reaction rates, properly orienting substrates for optimal interaction, desolvating substrates to remove interfering hydration shells, and stabilizing transition states. These mechanisms reduce the energy barrier for the reaction, allowing it to proceed more quickly and efficiently. Understanding these processes is essential for studying enzyme kinetics and their role in metabolic pathways.