BS problem on competitive inhibition~~

[johnwandering]

What type of regulation mechanism does letrozole (competitive inhibitor) use?
A allosteric inhibition
B allosteric activation
C feedback inhibition
D none of the above

Ill type the answer in a bit, just wondering what other people think...

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[MedPR]

What type of regulation mechanism does letrozole (competitive inhibitor) use?
A allosteric inhibition
B allosteric activation
C feedback inhibition
D none of the above

Ill type the answer in a bit, just wondering what other people think...

Going to guess D. Competitive inhibition is competitive inhibition. Allosteric inhibition is similar to non-competitive. I assume allosteric activation is the same, just an opposite effect. Feedback inhibition is similar to negative feedback (if not exactly the same thing).

 

[railgun]

What type of regulation mechanism does letrozole (competitive inhibitor) use?
A allosteric inhibition
B allosteric activation
C feedback inhibition
D none of the above

Ill type the answer in a bit, just wondering what other people think...

It's not B. It is probably A because it is the only answer that seems to answer the question - an allosteric inhibitor can be competitive. C seems unlikely as feedback inhibition may or may not mean competitive - it is more vague than A. It could be D, but it doesn't really answer the question well.
Where was this question? It seems passage based...

 

[chiddler]

What type of regulation mechanism does letrozole (competitive inhibitor) use?
A allosteric inhibition
B allosteric activation
C feedback inhibition
D none of the above

Ill type the answer in a bit, just wondering what other people think...

I think it's C. A competitive inhibitor in pathways goes back to inhibit stuff that made it without affecting the enzyme. It is obviously not allosteric since by definition competitive inhibitors cannot be allosteric.

But it seems bizarre to apply this logic to a drug. So i'm open to the possibility that D is right.

 

[MedPR]

My understanding of allosteric inhibition is pretty basic, but isn't it equivalent to noncompetitive inhibition, since it binds the allosteric site and not the active site?

 

[chiddler]

My understanding of allosteric inhibition is pretty basic, but isn't it equivalent to noncompetitive inhibition, since it binds the allosteric site and not the active site?

yes

 

[loveoforganic]

Not A - it binds the active site, not an allosteric site
Not B - same as A + it's inhibiting
Not C - it's not an endogenous product

Leaves D, although I'm not sure what answer they're looking for with that

 

[railgun]

My understanding of allosteric inhibition is pretty basic, but isn't it equivalent to noncompetitive inhibition, since it binds the allosteric site and not the active site?

I thought it could still be competitive, but indirectly? If it's competing for a site, its in competition no? For example, you have two sites - one active, one allosteric, the enzyme changes conformation if one binds. If allo inh. binds, it will prevent substrate to bind. If substrate binds, it prevents allo inh. to bind. Idk though i did this stuff 5 months ago.
Edit: checked on wiki and allosteric inhibitors can be competitive

 

[johnwandering]

wiki and allosteric inhibitors can be competitive

Can we get some direct MCAT perspective info on this?
I was under the deep impression that Allosteric inhibitors were NOT competitive.


Thanks everyone for your input.
The answer is D though.


I was confused at first but I understand now.
A and B are eliminated because it is stated that the inhibitor is competitive, not allosteric.
I thought it was C for some time, but it is not considering that letrozole is noted to be the "competitive inhibitor" and not the product.
So, D... none of the above.

Not C - it's not an endogenous product

What exactly is an "endogenous product"?

 

[MedPR]

I thought it could still be competitive, but indirectly? If it's competing for a site, its in competition no? For example, you have two sites - one active, one allosteric, the enzyme changes conformation if one binds. If allo inh. binds, it will prevent substrate to bind. If substrate binds, it prevents allo inh. to bind. Idk though i did this stuff 5 months ago.
Edit: checked on wiki and allosteric inhibitors can be competitive

Where on wiki does it say that allosteric inhibitors are competitive? The allosteric site is not the active site, and competitive inhibitors act at the active site. I'm 99.9% sure allosteric =/= competitive.

 

[MedPR]

Can we get some direct MCAT perspective info on this?
I was under the deep impression that Allosteric inhibitors were NOT competitive.


Thanks everyone for your input.
The answer is D though.


I was confused at first but I understand now.
A and B are eliminated because it is stated that the inhibitor is competitive, not allosteric.
I thought it was C for some time, but it is not considering that letrozole is noted to be the "competitive inhibitor" and not the product.
So, D... none of the above.


What exactly is an "endogenous product"?

An endogenous product is something your body produces. For example, there is feedback inhibition at the hypothalamus and anterior pituitary by LH.

 

[kasho11]

Fun fact, exogenous is something that comes from outside the body, for example during an experiment adding exogenous glucose to tissues.

But yeah competitive inhibitor means it competes directly for the active site of an enzyme. Things can get more complicated when considering enzymes with more than one active site and multiple regulatory and specificity roles, but for MCAT purposes, competitive is competitive. Allosteric is non-competitive.

 

[CopToEM]

What type of regulation mechanism does letrozole (competitive inhibitor) use?
A allosteric inhibition
B allosteric activation
C feedback inhibition
D none of the above

Ill type the answer in a bit, just wondering what other people think...

There's not enough information given for the answer to be feedback inhibition. Theres nothing which tells us what it inhibits and a feedback inhibitor is a product (or byproduct in a pathway) which inhibits its own production. Additionally it could be + or - and the question tells us none of that. That should rule that one out immediately. This is called a "detractor" answer.

Activation has nothing to do with inhibition in any case so that also eliminates that answer. Another detractor.

Allosteric inhibition is not a type of competitive inhibition. Competitive inhibition is when two ligands compete for a single binding site. IE. Ligand A has a higher affinity for the binding site than Ligand B and boots it out - thus outcompeting it.

Allosteric inhibition is when Ligand A binds a separate binding site than what Ligand B binds and causes a conformational change in Ligand B's binding site. Thus, the binding of Ligand A at another site causes the inactivation of binding site B. There is no direct competition for anything and thus allosteric != competitive as mentioned a few posts above.

The answer must be none of the above. The purpose of the question is simply to see if you know the difference between allosteric and competitive inhibition.

 

[railgun]

Where on wiki does it say that allosteric inhibitors are competitive? The allosteric site is not the active site, and competitive inhibitors act at the active site. I'm 99.9% sure allosteric =/= competitive.

http://en.wikipedia.org/wiki/Competitive_inhibition
last line on second para.
on the picture it says "allosteric competitive inhibition" for what i described before so I'm still not sure why you guys say it cannot be B.
(I already took the mcat, but im just curious, cuz i remember this from biochem)

 

[loveoforganic]

http://en.wikipedia.org/wiki/Competitive_inhibition
last line on second para.
on the picture it says "allosteric competitive inhibition" for what i described before so I'm still not sure why you guys say it cannot be B.
(I already took the mcat, but im just curious, cuz i remember this from biochem)

In virtually every case, competitive inhibitors bind in the same binding site as the substrate, but same-site binding is not a requirement. A competitive inhibitor could bind to an allosteric site of the free enzyme and prevent substrate binding, as long as it does not bind to the allosteric site when the substrate is bound.

Interesting, had forgotten about this

 

[hellocubed]

allosteric competitive inhibition

There are a lot of things outside the scope of the MCAT.

For the purposes of the MCAT, allosteric and competitive inhibition are two different processes

 

[MedPR]

http://en.wikipedia.org/wiki/Competitive_inhibition
last line on second para.
on the picture it says "allosteric competitive inhibition" for what i described before so I'm still not sure why you guys say it cannot be B.
(I already took the mcat, but im just curious, cuz i remember this from biochem)

Interesting, had forgotten about this

There are a lot of things outside the scope of the MCAT.

For the purposes of the MCAT, allosteric and competitive inhibition are two different processes

Oh, I see what you're talking about now. You're referring to this image, correct? http://en.wikipedia.org/wiki/File:Allosteric_comp_inhib_2.svg

I see that it does indeed say "Allosteric competitive" but in looking at the image and reading the description, how is that any different than non-competitive inhibition? I learned that non-competitive inhibition is binding of an inhibitor at the allosteric site thereby causing a conformational change in the active site. The hallmark of competitive inhibition is that it can be overcome by increasing substrate concentration, whereas non-competitive inhibition cannot. This "allosteric competitive" inhibition (to me) looks exactly like non-competitive inhibition.

I'm also done with MCAT, but I am curious about this since it seems no different than non-competitive inhibition.

 

[gettheleadout]

Oh, I see what you're talking about now. You're referring to this image, correct? http://en.wikipedia.org/wiki/File:Allosteric_comp_inhib_2.svg

I see that it does indeed say "Allosteric competitive" but in looking at the image and reading the description, how is that any different than non-competitive inhibition? I learned that non-competitive inhibition is binding of an inhibitor at the allosteric site thereby causing a conformational change in the active site. The hallmark of competitive inhibition is that it can be overcome by increasing substrate concentration, whereas non-competitive inhibition cannot. This "allosteric competitive" inhibition (to me) looks exactly like non-competitive inhibition.

I'm also done with MCAT, but I am curious about this since it seems no different than non-competitive inhibition.

This is my thinking as well.

Edit: Oh wow, this is weird but it explains it: http://assay.nih.gov/assay/index.php/Types_of_Inhibition#Allosteric_Inhibition

See Figures 1e and 2.

 

[loveoforganic]

Oh, I see what you're talking about now. You're referring to this image, correct? http://en.wikipedia.org/wiki/File:Allosteric_comp_inhib_2.svg

I see that it does indeed say "Allosteric competitive" but in looking at the image and reading the description, how is that any different than non-competitive inhibition? I learned that non-competitive inhibition is binding of an inhibitor at the allosteric site thereby causing a conformational change in the active site. The hallmark of competitive inhibition is that it can be overcome by increasing substrate concentration, whereas non-competitive inhibition cannot. This "allosteric competitive" inhibition (to me) looks exactly like non-competitive inhibition.

I'm also done with MCAT, but I am curious about this since it seems no different than non-competitive inhibition.

In allosteric competitive inhibition, the allosteric binder is kicked off upon binding of substrate (thus, you can saturate the enzyme and return to Vmax)

 

[chiddler]

In allosteric competitive inhibition, the allosteric binder is kicked off upon binding of substrate (thus, you can saturate the enzyme and return to Vmax)

then what does the allosteric binder do if it just gets kicked off right as substrate binds?

 

[MedPR]

In allosteric competitive inhibition, the allosteric binder is kicked off upon binding of substrate (thus, you can saturate the enzyme and return to Vmax)

But an allosteric inhibitor changes the structure of the active site, thus making it impossible for the substrate to bind.

 

[pfaction]

But an allosteric inhibitor changes the structure of the active site, thus making it impossible for the substrate to bind.

That's not what I learned, or the Km wouldn't be the same, right?

Allosteric allows the binding, but not the reaction to continue. That's why Km remains the same for Allosteric, but not competitive.

EDIT:

Here's TPR:

2nd edit: IS TPR WRONG OR AM I WRONG OR WHAT THE ****?

Everyone here is saying something different, and that wikipedia picture makes me confused as to what TPR says....

 

[chiddler]

pfaction is right

still confused what the point of allosteric inhibitor is if it just gets removed when substrate binds.

 

[MedPR]

I understand the point about non-competitive inhibition, but in that wiki image above it shows the allosteric competitive inhibitor as changing the active site thereby preventing the substrate from binding.

 

[chiddler]

i learned this from a freshman at my uni lol

https://en.wikipedia.org/wiki/Enzyme#.22Lock_and_key.22_model

apparently the lock and key model we learned in high school is not taught very much anymore because

"This is often referred to as "the lock and key" model. However, while this model explains enzyme specificity, it fails to explain the stabilization of the transition state that enzymes achieve."

the image is a misrepresentation of what happens.

 

[pfaction]

That's why I'm super confused. Here's a 100% thing we all agree on - noncomp inhibitors do NOT bind at active site, do NOT have same VMax compared to regular substrate-enzyme complex, and do NOT depend on saturation of substrate. If we agree on this, move forward:

Here's an if-then:

If: Allosteric inhibitors retain Km
Then: active site cannot be changed.

This brings up more questions from me, but do we agree here so far?

apparently the lock and key model we learned in high school is not taught very much anymore because

My biochem teacher used the "glove and hand" theory - a glove is a glove even when you crumple it, but when your hand starts to go in it, and some other stuff I can't remember because it looked like he was fisting the air.

 

[MedPR]

I don't understand what the invalidity/incompleteness of lock and key has to do with this though. I don't remember what I learned in high school, but I think my undergrad bio taught that lock and key was the popular idea that has since been disproven in favor of the induced fit model. I understand why this mechanism is called "allosteric competitive" inhibition. It's basically combining one aspect of allosteric inhibition (binding at a non-active site) and competitive inhibition (prevention of substrate binding).

The thing I don't understand is how allosteric competitive inhibition is overcome. Obviously if you dumped 50 enzymes, 500 substrates, and 1 allosteric competitive inhibitor in the same flask, the 500 substrates would outcompete the 1 inhibitor, but if you have 50 enzymes already bound to 50 allosteric competitive inhibitors, you could add 10^100 substrates and still have no reaction because the active site is changed. This seems similar to irreversible inhibition...?

 

[pfaction]

^ That's exactly why I'm confused there's a reaction at all with allosteric inhibition. I can understand competitive inhibition slowly rising as concentration increases.

popular idea that has since been disproven in favor of the induced fit model.

Agreed; the glove thing. Also things like COX-1 and COX-2 etc.

answer pm plz?

 

[chiddler]

If: Allosteric inhibitors retain Km
Then: active site cannot be changed.

Pretty sure you're right. Not 100% certain.

Medpr

It depends on type of inhibitor. Some bind strongly and take a lot to let go, and others bind weakly and therefore let go easily. Thus why some inhibitors more effective than others. It can be irreversible if I remember correctly, too. Like cyanide.

The point I was making with the discrepancy of model and image is that the image you posted uses lock and key image, not induced fit. So it can not be taken literally that when an inhibitor binds, substrate cannot bind.

 

[MedPR]

Pretty sure you're right. Not 100% certain.

Medpr

It depends on type of inhibitor. Some bind strongly and take a lot to let go, and others bind weakly and therefore let go easily. Thus why some inhibitors more effective than others. It can be irreversible if I remember correctly, too. Like cyanide.

The point I was making with the discrepancy of model and image is that the image you posted uses lock and key image, not induced fit. So it can not be taken literally that when an inhibitor binds, substrate cannot bind.

Oh I see what you mean. If you don't take it literally, though, then what differentiates allosteric competitive from non-competitive? Both bind at an allosteric site. Are you thinking that allosteric competitive changes the active site, but not so much that the substrate is unable to bind, just less-able to bind?

 

[chiddler]

Oh I see what you mean. If you don't take it literally, though, then what differentiates allosteric competitive from non-competitive? Both bind at an allosteric site. Are you thinking that allosteric competitive changes the active site, but not so much that the substrate is unable to bind, just less-able to bind?

i was thinking that it prevents conformational change somehow. we know that Km doesn't change so surely binding is not affected. so it must be change after binding, probably.

also looking it up cyanide is not "permanently irreversible", it just binds so strongly that need drugs which bind more strongly to CN than whatever cytochrome protein CN blocks.

 

[gettheleadout]

Did nobody read my post?

 

[chiddler]

Did nobody read my post?

i missed it.

1. "I binding can result in a conformational change that prevents S binding (and vice versa)."

OK! So if substrate binds, it doesn't just kick inhibitor out as was suggested above!

But what does this say about Km? Doesn't this contradict that Km doesn't change with non-competitive inhibitors?

2. I'm worried about this one:

Wikipedia: "In biochemistry, allosteric regulation is the regulation of an enzyme or other protein by binding an effector molecule at the protein's allosteric site (that is, a site other than the protein's active site)."

link: "An allosteric inhibitor decreases activity by binding to an allosteric site, other than or in addition to the active site on the target."

!?!

 

[gettheleadout]

i missed it.

1. "I binding can result in a conformational change that prevents S binding (and vice versa)."

OK! So if substrate binds, it doesn't just kick inhibitor out as was suggested above!

But what does this say about Km? Doesn't this contradict that Km doesn't change with non-competitive inhibitors?

2. I'm worried about this one:

Wikipedia: "In biochemistry, allosteric regulation is the regulation of an enzyme or other protein by binding an effector molecule at the protein's allosteric site (that is, a site other than the protein's active site)."

link: "An allosteric inhibitor decreases activity by binding to an allosteric site, other than or in addition to the active site on the target."

!?!

1. Correct. Allosteric inhibitor binding does not necessitate release of the substrate. See the equilibrium state found in Figure 2.

2. When they say "in addition to" they mean it binds to both an allosteric site and the active site. See Figure 1d at the NIH link.

 

[chiddler]

1. Correct. Allosteric inhibitor binding does not necessitate release of the substrate. See the equilibrium state found in Figure 2.

2. When they say "in addition to" they mean it binds to both an allosteric site and the active site. See Figure 1d at the NIH link.

Regarding #2, I understand what is meant. I was trying to illustrate that the two definitions I quoted are incompatible.

Wiki says that allosteric is a site other than active site.

The NIH says that it can be active site or other than active site.

 

[CopToEM]

i learned this from a freshman at my uni lol

https://en.wikipedia.org/wiki/Enzyme#.22Lock_and_key.22_model

apparently the lock and key model we learned in high school is not taught very much anymore because

"This is often referred to as "the lock and key" model. However, while this model explains enzyme specificity, it fails to explain the stabilization of the transition state that enzymes achieve."

the image is a misrepresentation of what happens.

Yes, this is right and apparently the information about allosteric competitive inhibition is also right. The thing you're all forgetting is that this is the MCAT consisting of Gen Chem, Gen Bio, Physics, and Organic. As with all things academic, they teach things to you simply and then later down the road you learn about all of the exceptions.

In Gen Bio they told us that DNA is, in many regards, a static genomic code. Now, in Immunology and Molecular Genetics we learn about VDJ Recombination and Transposons which challenge everything they told us 3-4 years ago.

For the purposes of the MCAT you cannot (and should not) pick out exceptions from upper level courses. When you're taking the test you must think like an individual who has had only the four required courses.

 

[Morsetlis]

The answer is D. I'm not sure what the confusion is. Even if there are multiple partially correct answers, you must choose the best answer.

In general bio I also remember learning about ferns and flowers. Not sure any of that remains applicable now...

 

[railgun]

Ok I think I'll explain for people who want to know (Probably not required in detail for mcat as people are saying.)
1. Regular competition: both substrate and inhibitor compete for same binding site

2. Allosteric competition: substrate and inhibitor compete for a binding site.
So basically, for allosteric competition they are competing for a spot because if one binds the other cannot bind. If you have a substrate bound at active site, inh cannot bind at allo site. If you have a inh bound at allo site, substrate cannot bind at active site.

3. Non-competitive:

Non-competitive inhibition is a type of enzyme inhibition where the inhibitor reduces the activity of the enzyme and binds equally well to the enzyme whether or not it has already bound the substrate.

If any of this is wrong, feel free to correct me. I just didn't like this question... because i would have probably got it wrong.

 

[Morsetlis]

Don't confuse allosteric regulation and noncompetitive inhibition.

An irreversible ant/agonist that binds at the same binding site as the agonist is also noncompetitive! For example: Suxamethonium/succinylcholine depolarizes the NmAChR, mimicking the action of endogenous Ach, but is a noncompetitive antagonist to Ach! Luckily, even though it cannot be removed by Ach, it can be removed by AchEsterase.

Allosteric regulation is also noncompetitive: cAMP allosterically activates PKA, but PKA's active site is not where cAMP binds.

It is not necessary to remember specific examples.