allosteric effect/ noncompetitive inhibition & Vmax

[SaintJude]

Although, generally, noncompetitive inhibition does change Vmax, allosteric regulation is a special circumstance.
An allosteric enzyme inhibitor is a case of noncompetitive binding that can be overcome by additional substrate--so it does NOT change Vmax. Is that right?

Reference:
http://www.biology.arizona.edu/biochemistry/problem_sets/energy_enzymes_catalysis/03t.html

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[chiddler]

Noncompetitive inhibition does change Vmax, correct. Noncompetitive inhibition is when the inhibitor binds allosterically by definition:

"Non-competitive inhibition is a type of enzyme inhibition where the inhibitor reduces the activity of the enzyme, by binding not to the active site on the enzyme, but to a different site." (wiki)

If it binds to the active site, then it is a competitive inhibitor. So an allosteric enzyme inhibitor is a case of noncompetitive binding, as you wrote. However, you're mistaken in that it cannot be overcome by additional substrate and it does change Vmax.

The reason that competitive inhibitors do not alter Vmax is that with enough substrate, the inhibitor becomes a very small proportion of the solution so the chances of it interacting with enzyme become less and less as substrate concentration increases. Non competitive bind directly to enzyme without fighting for the active site. So increasing substrate concentration will not have much of an effect on inhibitor since they are not competing. Vmax is thus decreased.

 

[SaintJude]

Nah, that's what I thought before I knew better. Allosteric regulation does not change Vmax. I'm sticking to my story.
I just had a question testing this concept. Allosteric enzymes can have multiple active sites and their reaction velocity depends on more than the concentration of one substance. Check my reference or any other biochem book showing the sigmoidal shape of allosteric enzymes

Someone back me up before chiddler smacks me

 

[saoj]

Nah, that's what I thought before I knew better. Allosteric regulation does not change Vmax. I'm sticking to my story.
I just had a question testing this concept. Allosteric enzymes can have multiple active sites and their reaction velocity depends on more than the concentration of one substance. Check my reference or any other biochem book showing the sigmoidal shape of allosteric enzymes

Someone back me up before chiddler smacks me

If there was a recent discovery that changed everything, I would stick with the old understanding, at least for the MCAT. Go for what the review books tell you.

 

[chiddler]

lol

 

[theseeker4]

Nah, that's what I thought before I knew better. Allosteric regulation does not change Vmax. I'm sticking to my story.
I just had a question testing this concept. Allosteric enzymes can have multiple active sites and their reaction velocity depends on more than the concentration of one substance. Check my reference or any other biochem book showing the sigmoidal shape of allosteric enzymes

Someone back me up before chiddler smacks me

Noncompetitive inhibition does change Vmax, correct. Noncompetitive inhibition is when the inhibitor binds allosterically by definition:

"Non-competitive inhibition is a type of enzyme inhibition where the inhibitor reduces the activity of the enzyme, by binding not to the active site on the enzyme, but to a different site." (wiki)

If it binds to the active site, then it is a competitive inhibitor. So an allosteric enzyme inhibitor is a case of noncompetitive binding, as you wrote. However, you're mistaken in that it cannot be overcome by additional substrate and it does change Vmax.

The reason that competitive inhibitors do not alter Vmax is that with enough substrate, the inhibitor becomes a very small proportion of the solution so the chances of it interacting with enzyme become less and less as substrate concentration increases. Non competitive bind directly to enzyme without fighting for the active site. So increasing substrate concentration will not have much of an effect on inhibitor since they are not competing. Vmax is thus decreased.

Allosteric inhibition, as discussed in the reference, is a special case of non-competitive inhibition. Sure, the effect on the active site by non-competitive inhibition is an allosteric effect, but that is not synonymous with allosteric inhibition.

There are multiple binding sites in allosteric enzymes, and substrate binding to one of those sites increases the affinity of the other sites for additional substrate (and at the same time reduces the affinity of the enzyme for the inhibitor) meaning the normal rules do not apply.

 

[SaintJude]

Thanks.

P.s. This was the test question (same exact one as in Kaplan)

http://www.biology.arizona.edu/biochemistry/problem_sets/energy_enzymes_catalysis/03Q.html

 

[cma116]

Hey guys - I know this is a very old thread, but it still appeared in the top few google searches when I was trying to figure out why Vmax decreases in noncompetitive inhibition, but stays the same in allosteric inhibition, since both involve an inhibitor binding to the enzyme's allosteric site. I believe that I can explain why...

In non-competitive inhibition, even though the inhibitor binds to an allosteric site, it does not prevent the substrate from binding to the active site; it simply prevents the enzyme from performing its activity necessary to proceed with the catalytic reaction. This is why raising the substrate concentration in noncompetitive inhibition will not stop inhibitors from binding -- inhibitors here can bind to either an enzyme or an enzyme-substrate complex. Any Enzyme or ES complex that is bound to an inhibitor in this situation will be useless, which is why the Vmax will decrease -- there are less available enzymes to catalyze the reaction, so it will proceed at a slower rate.

On the other hand, in allosteric inhibition, inhibitors and substrates are COMPETING to bind to the allosteric enzyme, but THEY ARE NOT COMPETING FOR THE SAME BINDING SITE. There are both inhibitor binding sites and substrate binding sites. When one type of these (inhibitor or substrate) binds to the allosteric enzyme at its respective binding site, it induces the enzyme to be in either its relaxed (active) or taut (inhibited) form, which will allow more of the same type to bind to it (cooperative binding). Therefore, if you greatly increase the substrate concentration with an allosteric enzyme, it is more likely that a substrate will bind to the enzymes than an inhibitor, which is why allosteric inhibition CAN be overcome with increased substrate concentration -- which is why Vmax does not change in allosteric inhibition.

Hope this helps -- explaining it on here definitely helped me to better understand it!