Enzymes question

[vectorman]

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What is the difference between allosteric regulation (can change both Vmax and Km) and regular competitive(change only Km) and non competitive inhibitors (change only Vmax)? I just don't seem to have a firm grasp on this topic I would appreciate it someone could help me out. Thanks in advance.

 

[TawMus]

What is the difference between allosteric regulation (can change both Vmax and Km) and regular competitive(change only Km) and non competitive inhibitors (change only Vmax)? I just don't seem to have a firm grasp on this topic I would appreciate it someone could help me out. Thanks in advance.

From what I understand, allosteric regulation = non competitive inhibitors, which decrease Vmax but Km remains the same. Competitive inhibitors cause Km to increase but Vmax remains the same because you can add more substrate to "out compete" the competitive inhibitors.

 

[sleepy425]

What is the difference between allosteric regulation (can change both Vmax and Km) and regular competitive(change only Km) and non competitive inhibitors (change only Vmax)? I just don't seem to have a firm grasp on this topic I would appreciate it someone could help me out. Thanks in advance.

The thing is, I hate the term allosteric regulation. All it means is that the regulator binds somewhere other than the active site. That's all. The regulator can be an activator or an inhibitor.

The problem with the term allosteric inhibition is that it is kinetically meaningless. It doesn't tell you anything about how it affects the kinetic parameters.

The truth is, there are three basic, meaningful types of inhibition (there are actually more complicated ones, but they're all related to these three types):
1. Competitive inhibition-inhibitor binds only the free enzyme
2. Uncompetitive inhibition-inhibitor binds only the enzyme-substrate complex
3. Noncompetitive inhibition-inhibitor binds both the free enzyme and the enzyme-substrate complex.

An allosteric inhibitor can exhibit any of the three inhibition patters. For example, if an inhibitor only binds an allosteric site on the free enzyme but not on the enzyme substrate complex, it is a competitive inhibitor. If an inhibitor binds an allosteric site on the enzyme substrate complex but not on the free enzyme, then it is an uncompetitive inhibitor. If an inhibitor binds an allosteric site on both free enzymea nd enzyme substrate complex, it's a noncompetitive inhibitor.

So an allosteric inhibitor CAN change the Vmax, and it CAN change the Km, but it just depends on the type of inhibition. A competitive inhibitor only affects Km (it raises it). A noncompetitive inhibitor can lower both Km and Vmax, but there is a special case where a noncompetitive inhibitor can lower just the Vmax (although this is never encountered). Actually, the definition I often see for noncompetitive inhibition is that it just lowers Vmax only, but that's just silly. That only occurs if the inhibitor binds the free enzyme and the enzyme substrate complex with equal affinity. If they don't have equal affinity, it's often called mixed-type inhibition, but mixed type inhibition is just the practical case of noncompetitive inhibition. If the affinity isn't the same, then you have lower Km and Vmax. Like I said, I'm sure this is different from what is taught in classes, but if you want me to explain my views on this I can.

An uncompetitive inhibitor lowers both Km and Vmax. I should add that these effects should NOT be memorized. If you want me to show you how to learn them, and never forget them, I can, just PM me.

 

[vectorman]

Never heard of uncompetitive inhibitor in any of the books im lookin at.

 

[sleepy425]

Never heard of uncompetitive inhibitor in any of the books im lookin at.

It just fills in the gap that competitive inhibition and noncompetitive inhibition create because you've gotta have a type of inhibitor that binds the enzyme substrate complex only. A lot of times, an inhibitor will be competitive with respect to one substrate but uncompetitive with respect to the other. This happens a lot when the substrates bind in a specific order. For example:

Say you have two substrates, A and B. Substrate A binds first, and B can't bind until A binds. Ok, so now I have an inhibitor that binds where substrate B binds. If I do the reaction where I keep substrate A at high concentrations and vary concentrations of B, I will most likely see competitive inhibition, because there's plenty of A around at all times to open the door for B or the inhibitor that competes with B to bind. On the other hand, if I keep the concentration of B high, and I vary the concentration of A, I will more than likely see uncompetitive inhibition because as I increase the concentration of A, it increases the ability of both B and the inhibitor to bind. Thus, the inhibitor binds only when concentrations of A start to get high enough, and that's the hallmark of an uncompetitive inhibitor. So even though it binds in the same way and to the same place, the inhibition pattern is different with respect to different substrates because it actually competes with B for binding, but binding of A helps the inhibitor bind so it's competitive with respect to B, but uncompetitive with respect to A.

 

[AsuKa]

wow should we know which type of inhibition leads to an increase/decrease in km and vmax ?

i used to know it from biochem, but i forgot it awhile ago 🙁

 

[sleepy425]

wow should we know which type of inhibition leads to an increase/decrease in km and vmax ?

i used to know it from biochem, but i forgot it awhile ago 🙁

well, i'm not sure if you need to know it or not, but here's an easy way to remember:

if the Vmax is affected, it's going to go down because, well, it's an inhibitor. if Vmax went up it'd be an activator. Km on the other hand is a little more complicated, but if you look at it this way it's straightforward:

Km is a dissociation constant. it describes the breakdown of the enzyme substrate complex, either to the free enzyme and the product, or to the free enzyme and the substrate. so Km goes up when breakdown of the ES complex goes up and/or formation of ES goes down. Km goes down when breakdown of the ES complex goes down and/or formation of ES goes up.

now you can tell what the effect on Km will be. a competitive inhibitor binds the free enzyme only, and since an inhibitor inhibits change, it's going to prevent the free enzyme from forming the ES complex. so formation of the ES goes down, and thus Km goes up.

for an uncompetitive inhibitor, it binds the ES complex only, and since an inhibitor inhibits change, it's going to prevent the ES from breaking down. that means that there's less dissociation of ES and thus the dissociation constant Km goes down.

for a noncompetitive inhibitor, this is trickier. if the inhibitor has the same affinity for the free enzyme as for the ES complex, then there's no change in Km because binding to the ES complex decreases the rate of ES breakdown, but binding to the free enzyme decreases the rate of ES formation too, so there's no net change in the Km. if the affinity for the free enzyme is higher, Km goes up because you have more inhibitor binding to the free enzyme than to the ES complex. if the affinity for the ES complex is higher, Km goes down because you have more inhibitor binding to the ES than to the free enzyme.

so that's all there is to it. just remember that Km describes breakdown of ES, so higher Km means higher breakdown or lower formation. then look at where the inhibitor binds. the inhibitor binding to the free enzyme will make Km go up because it lowers formation of ES. the inhibitor binding to the ES will make Km go down because it lowers breakdown of the ES. the inhibitor binding to both will have different effects depending on the situation

 

[AsuKa]

a little confusin at first, but i got it 🙂 thx