AAMC FL1 Bio #39

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ponyprincess
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AAMC FL1 Bio #39

Postby ponyprincess » Sun Aug 13, 2017 10:37 pm

Hello, I'm having a hard time with the following question:

In Passage 7, we are given the following information:

*** cP-450 metabolizes lipid-soluble toxins

***cP-450 is inducible by new toxins/increased concentrations of toxin

***cP-450 is important in barbiturate metabolism, and alcohol (a product of "Reaction 1" is a competitive inhibitor)

We are then given a scenario. A sober alcoholic takes the recommended dosage of barbiturates, but does not feel its effects. So, he takes more sleeping pills and has an alcoholic beverage. He then dies due to the alcohol in his system (which we can infer inhibited the cP-450).



Question 39: No drowsiness was initially felt by the alcoholic because the previous abuse of alcohol had:

The answer is "induced the cP-450."
It is obvious that we need more cP-450 in order to metabolize the barbiturates so quickly (hence, why he felt no effect initially).
But, the passage does state that cP-450 metabolizes LIPID soluble toxins. 1) Alcohol is not lipid soluble. 2) alcohol is a PRODUCT of the reaction w/ cP-450. 3) the passage never states that cP-450 is involved with alcohol metabolism.

Pls help :) How is this possible?
Thanks!
NS_Tutor_Andrew
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Re: AAMC FL1 Bio #39

Postby NS_Tutor_Andrew » Mon Aug 14, 2017 11:55 am

Hi ponyprincess,

Excellent question! The best way to approach this question is by very carefully leveraging what they give you in the passage. The key pieces of information are:

(1) cP-450 is inducible.
(2) Ethanol is a competitive inhibitor of cP-450 (which tells you that EtOH interacts with the active site of cP-450).
(3) The alcoholic did not immediately feel the effects of barbiturates, which are metabolized by cP-450. This tells you that cP-450 was induced/overexpressed in this individual.
(4) After consuming ethanol (the competitive inhibitor of cP-450), the individual died of an overdose of barbiturates.

Putting the pieces together, the idea is that previous alcohol abuse induced cP-450 to the point that the individual had a surplus of cP-450 available at first, meaning that he did not feel the effects of the barbiturates. Then the EtOH jumped in and served as a competitive inhibitor of cP-450, meaning that it was no longer available to metabolize the excess barbiturates, leading to a barbiturate overdose. With this in mind, D is correct.

In your comment, you mention that the individual died to an alcohol overdose. This is incorrect. The individual died of a barbiturate overdose. This point may be key to understanding the question, so see if it makes more sense in that light.

You can also approach this question by process of elimination. A and C can be quickly eliminated because they have no support. The passage does talk about EtOH's role in inhibiting and inducing cP-450 -- but the Q specifically asks about previous EtOH abuse, which eliminates B and leaves D.

Now, to answer your points more specifically...

(1) Ethanol actually is lipid-soluble (https://www.chem.fsu.edu/chemlab/chm104 ... cess.html; see also https://www.ncbi.nlm.nih.gov/pubmed/9164559 to get a sense of how different alcohols have different lipid solubility profiles); this fact isn't generally emphasized in MCAT review & can be inferred by the passage, so I'm just providing the citations FYI.

(2) Alcohol isn't a product of the cP-450 reaction. Look carefully at Reaction 1—R-OH does not generally mean "EtOH." This reaction would give us some support for thinking that cP-450 could oxidize ethane to alcohol, but there's no discussion of ethane in the passage (plus ethane would be a gas at physiological temperature, and if we're dealing with ethane poisoning, we'd have a lot of other problems too).

(3) True, but by stating that EtOH is a competitive inhibitor of cP-450, the passage does tell us that EtOH interacts with the active site of cP-450. That, plus the discussion of induction, allows us to infer that cP-450 must be involved in EtOH metabolism.

Hope this helps & best of luck!
Andrew D.
Content Manager, Next Step Test Prep.
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ponyprincess
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Re: AAMC FL1 Bio #39

Postby ponyprincess » Wed Aug 16, 2017 6:23 pm

Cool thanks Andrew, this is really helpful! :)

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