Enzyme Kinetics: Identify the type of enzyme

[SaintJude]

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Mini passage paragraph.

Q: Based on the info from the passage & table above, what type of effect does Tacrine demonstrate?

A. Irreversible inhibition
B. Reversible competitive inhibition
C. Reversible noncompetitive inhibition
D. Allosteric activation

I'm conflicted between A & C. What would make you lean towards one or the other? I'll post the answer later...

 

[chiddler]

Since increasing the concentration of substrate doesn't change velocity of reaction, it should be non competitive inhibition.

But i've never really read about non-reversible inhibitors. What are their characteristics? I'm not sure about A vs C either, but i'd guess that it is reversible because passage says that galantamine is a similar inhibitor that is reversible.

 

[MedPR]

I would guess C. If you induced an irreversible AchE inhibitor, Ach would never be cleaved and would always be in the NMJ = continuous stimulation = continuous muscle contraction = bad.

And yes, as chiddler said, this cannot be competitive inhibiton. At first I was really confused because the [Tacrine] in tube 5 looks like it is 1.0*10^-1, but after I squinted a bit I can see tha tit is 10^-4.

Also, spoiler: http://en.wikipedia.org/wiki/Tacrine

 

[SaintJude]

Answer is C. But the last sentence of passage says that "other types of AchE inhibitors like Tacrine" so I took it literally and thought types other than reversible....and thus leaned towards A....

If it had said, "similar types" I would chosen C too (but I guess losers always have excuses...) darn. What is wrong with my reasoning ?

 

[lkthlttr]

Answer is C. But the last sentence of passage says that "other types of AchE inhibitors like Tacrine" so I took it literally and thought types other than reversible....and thus leaned towards A....

If it had said, "similar types" I would chosen C too (but I guess losers always have excuses...) darn. What is wrong with my reasoning ?

Yes and a non-competitive inhibitor is a different type of inhibitor compared to a competitive inhibitor. Don't try to read context into the wording where there is none. As to the question, to establish that an inhibitor is an irreversible inhibitor, you would need time course data, which is not given in this table. Because of that and the reasons given by chiddler, I too would have leaned toward non-competitive as the answer.

 

[SaintJude]

. As to the question, to establish that an inhibitor is an irreversible inhibitor, you would need time course data, which is not given in this table. .

Why do you need time course data to conclusively establish it's an irreversible inhibitor? When you say "time course", you mean like the picture below, where it shows that how much product was formed in a certain amount of time?

Why isn't it enough to see that the [Ach] doubled between Tube 3 & 5 and Vmax still stayed the same?

Graph below:
Cerulenin (&#9632😉 is an irreversible inhibitor & absence of inhibitors (&#9652😉

 

[MedPR]

Answer is C. But the last sentence of passage says that "other types of AchE inhibitors like Tacrine" so I took it literally and thought types other than reversible....and thus leaned towards A....

If it had said, "similar types" I would chosen C too (but I guess losers always have excuses...) darn. What is wrong with my reasoning ?

Yes, but why would you want to irreversibly inhibit AchE? If you do that, you would never remove Ach from synaptic junctions. That's bad.

 

[SaintJude]

Yeah, in relation to Alzheimer's and this paragraph I understand now that you still need some Ach. In fact, in all conditions, you probably still need some Ach since it's such a common neurotransmitter in the brain.

However, I'd still don't understand why you MUST have time course data to experimentally prove the presence of a irreversible inhibitor.

 

[MedPR]

Yeah, in relation to Alzheimer's and this paragraph I understand now that you still need some Ach. In fact, in all conditions, you probably still need some Ach since it's such a common neurotransmitter in the brain.

However, I'd still don't understand why you MUST have time course data to experimentally prove the presence of a irreversible inhibitor.

I guess you could have other forms of data as well, but if you showed that over a long period of time the inhibitor never released, it would be evidence that it is irreversible.

Alternatively you could put a receptor + inhibitor, then add some enzyme or hormone that you expect to reverse the inhibition. If that doesn't work, then you might have an irreversible inhibitor.

 

[MrNeuro]

Why do you need time course data to conclusively establish it's an irreversible inhibitor? When you say "time course", you mean like the picture below, where it shows that how much product was formed in a certain amount of time?

Why isn't it enough to see that the [Ach] doubled between Tube 3 & 5 and Vmax still stayed the same?

Graph below:
Cerulenin (&#9632😉 is an irreversible inhibitor & absence of inhibitors (&#9652😉

tube 3 to 5 in my opinion hints that its a NONCOMPETITIVE inhibitor and would strongly suggest C as a best answer choice

Yes, but why would you want to irreversibly inhibit AchE? If you do that, you would never remove Ach from synaptic junctions. That's bad.

its used in Alzheimer's patients, whom mainly suffer from brain related neurological disorders assuming that this drug is specific to the brain and not the rest of the body (unlikely but not impossible) so a drug that irreversibly affects AchE activity is sort of a 1 time thing and in some cases may be preferred rather than consistently taking a an AchE inhibitor.

Yeah, in relation to Alzheimer's and this paragraph I understand now that you still need some Ach. In fact, in all conditions, you probably still need some Ach since it's such a common neurotransmitter in the brain.

However, I'd still don't understand why you MUST have time course data to experimentally prove the presence of a irreversible inhibitor.

time course data may help you see that over time that even after the half-life of a drug has passed the effects should still remain where as with a reversible noncompetitive inhibitor the effects will remain as long as the half-life and maybe shortly thereafter and usually will return back to baseline levels after an extended period of time...

example of a irreversible inhibitor-like drug botulinum toxin (aka active ingredient in Botox)

 

[SaintJude]

Yeah, I understand why now. The effect of an irreversible inhibitor can only be prove over time. A reversible inhibitor, just like an irreversible inhibitor, can lower the reaction velocity...it just doesn't do it permanently.
This table isn't enough because it shows the reaction velocity at one particular time, not the Vmax.

 

[lkthlttr]

Why do you need time course data to conclusively establish it's an irreversible inhibitor? When you say "time course", you mean like the picture below, where it shows that how much product was formed in a certain amount of time?

No, I meant something like the following, in which you compare the activity of the enzyme after treating with the irreversible inhibitor for a period of time (the various curves are different concentrations of inhibitor... any one curve would be sufficient to demonstrate irreversible inhibition):

Why isn't it enough to see that the [Ach] doubled between Tube 3 & 5 and Vmax still stayed the same?

But for the purposes of the MCAT, I think you can just assume that since irreversible inhibition takes place in the active site, that it will act like a competitive inhibitor and disregard the kinetics of inactivation.