Biochemistry Enzymes V: Enzyme Inhibition

Hello and welcome back to Educator.com, and welcome back to Biochemistry.0000

Today, we are going to continue our discussion of enzymes by talking about enzyme inhibition.0004

Enzyme inhibition exactly is exactly what you think it is.0009

We have an enzyme that does something; we want to either completely stop it from doing something, or we want to slow it down a little bit.0014

There is also something called positive inhibition, where you want to actually cause an enzyme to do what it does a little bit better, a little bit faster; but for the most part, we are going to be talking about negative inhibition.0022

Again, inhibition, exactly what you think it means, so let's get started and see what we can do.0036

OK, enzyme inhibitors - excuse me - are molecules that interfere with enzyme action or enzyme activity.0043

Now, it is no surprise that a large percentage of current pharmaceuticals on the market are, in fact, enzyme inhibitors, and that is a huge, huge, huge area or pharmaceutical research.0076

We discover some metabolic pathway; we discover something in that pathway, some enzyme where we know how to control it.0117

We control it; we mess with it- that is what we do.0125

OK, now, there are 2 broad classes of enzyme inhibitors.0128

Excuse me; we have something called reversible and - exactly what you think - irreversible.0140

Now, let's go ahead and deal with the reversible first; let me go ahead and do this in blue.0152

Now, the reversible comes in 3 varieties: something called a competitive inhibitor - it is exactly what you think it is, but we will give a definition in just a minute - and uncompetitive inhibitor and a mixed inhibitor- mixed being combination of competitive and uncompetitive.0161

OK, let's go ahead and deal with these one at a time; the first thing we are going to deal with is competitive inhibition.0187

It is the most intuitive one; the one that is most easily understood.0194

Competitive inhibition is exactly what you think it is, exactly what it sounds like.0199

It is where the inhibitor, which again is a molecule, where the inhibitor molecule, it competes directly against...I will stay with actually, instead of against, does not matter.0212

It is competing with the normal substrate for binding to the active site.0239

It competes directly with the normal substrate for the active site.0244

They both want to be in the active site- substrate competitor.0260

If substrate makes it, the enzyme does what it does; if the competitor makes it to the active site before the substrate does, that is it.0264

It blocks off entrance to the active site for the normal substrate.0271

Excuse me; pictorially, it looks something like this.0279

Let's say you have some enzyme, it looks something like this.0284

OK, excuse me.0290

Let's say our normal substrate looks like that.0295

When the enzyme and the substrate come together - I will put S here, and I will put E for enzyme - we end up with our enzyme substrate complex.0300

Well, the inhibitor, let's say it looks something like that.0312

Now, if the enzyme binds to the inhibitor, you end up with something called the enzyme...this is the enzyme substrate complex.0323

You end up with something called an enzyme inhibitor complex, and now, because this inhibitor is occupying the actual active site of the enzyme, the substrate, itself, cannot come in.0338

It has blocked the enzyme it has inhibited- that is it.0349

Whatever metabolic pathway happens to be involved, it stops at that pathway.0352

It does not do what it is supposed to do; this is competitive inhibition- competition for the active site.0357

In terms of the Es and Ss that we were talking about, before it looks something like this.0364

You have the enzyme plus you have the substrate.0368

They can form something called the enzyme substrate complex that can go on to form enzyme plus product.0372

Now, the enzyme, instead of binding to the substrate, can also bind to the inhibitor forming the enzyme inhibitor complex.0378

This is what it looks like in terms of Es and Ss and things like that.0388

Now, let's go ahead and for this, I am going to introduce something called k_i.0393

I just want you to be aware of it; I will write it again.0400

This k_i is not a rate constant; this is an equilibrium constant.0405

Here, this k_i is equal to the concentration of E_i over the concentration of E times the concentration of I.0411

That is this reaction right here, the equilibrium.0425

It is the dissociation reaction for the enzyme inhibitor complex- OK, products over reactants.0429

These are the reactants; this is the product.0436

This k_i, it is the equilibrium constant for the formation of enzyme inhibitor complex, or it is the dissociation constant, if you will, for this complex that way, depending on which direction you want to take it.0438

It is just an equilibrium complex; OK, it will show up a little bit later, but we are not really going to be doing too much with it.0451

It is just something that you should know.0458

OK, now, the Michaelis-Menten equation in the presence of a competitive inhibitor looks like this: v₀ = V_max S, so far so good, alpha K_m + S.0462

Now, we have this alpha factor; here, alpha is equal to 1 plus the concentration of inhibitor, oops, k_i not K_m, right?0505

Yes, they were k_i, and k_i, as we said, is equal to E_i/E and I.0523

These do not matter all too much; this is what is important, this alpha.0543

Just consider it some number, which is generally going to be bigger than 1.0548

It is the whole idea; it is going to be bigger than 1.0552

OK, it is just some factor, which in this case, is related to the inhibition.0555