AAMC C/P Section Bank Passage 5 pls help!!

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alyxxs

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I am so confused by this passage and what the questions are asking me. Someone pls shed some light on this.

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This is a question that is super overwhelming, if you read the whole thing.
So don't 🙂

Let's just look at Table 1. We see wild-type and variants, which means that there must be some genetic differences in the variants. In this case, the variants are single amino acid substitutions.
Ex. H80A means that at position 80 (top-left of molecule), a Histidine was replaced with an Alanine. D113A means that at position 113 (top-middle) a Aspartate was replaced with Alanine, and for E148A, Glutamate at position 148 (bottom-left) is replaced by an Alanine.
We also have two enzyme kinetic parameters you should know, along with melting point measurements.

Q36: Answer by comparing Alanine vs Histidine/Aspartate/Glutamate
Q38: Answer by comparing Glutamate vs Aspartate and how it relates to the loss of catalytic activity
Q39: Answer by understanding the changes in Kcat and Km as presented in the table and how that is interpreted as measures of substrate binding and catalytic turnover
 
This is a question that is super overwhelming, if you read the whole thing.
So don't 🙂

Let's just look at Table 1. We see wild-type and variants, which means that there must be some genetic differences in the variants. In this case, the variants are single amino acid substitutions.
Ex. H80A means that at position 80 (top-left of molecule), a Histidine was replaced with an Alanine. D113A means that at position 113 (top-middle) a Aspartate was replaced with Alanine, and for E148A, Glutamate at position 148 (bottom-left) is replaced by an Alanine.
We also have two enzyme kinetic parameters you should know, along with melting point measurements.

Q36: Answer by comparing Alanine vs Histidine/Aspartate/Glutamate
Q38: Answer by comparing Glutamate vs Aspartate and how it relates to the loss of catalytic activity
Q39: Answer by understanding the changes in Kcat and Km as presented in the table and how that is interpreted as measures of substrate binding and catalytic turnover


Thank you!! After doing more problems I was able to understand what the question was asking and got the correct answers. My trouble was coming from the labels for the variants, I never knew the letters were representative of the amino acid substitutions. Thanks for your response!
 
39 is pretty straight forward if you know the alternative names.

It is asking what the data says about substrate binding, which is just the Km value. Are the Km values for the variants different or the same compared to the wild type? If they are different, then substrate binding is impacted.
Next it asks about catalytic turnover, which is just the Kcat values. Clearly they are changing as well.

The point of this question I think is two fold.

1. Do you know what the terms for Michaelis Menten kinetics are and
2. Do you recognize that when numbers start adding exponents that they are exponentially different. For example, the Km quadruples for the 1st variant but the Kcat decreases by a bunch more (39 vs .016, which is > 2000 fold decrease)

Here is how I would approach this if I was clueless though. They are asking about two values and how they change/relate to one another. Neither of those values are temperature so you can deduce that they are talking about Kcat and Km. Since they both change, you can quickly rule out C and D. At this point you have a 50/50 shot. Common sense would tell you that K(cat) is more likely to be related to catalytic turnover and you can tell those value vary more. Thus, if you had never seen M-M kinetics before, using some basic reasoning you could still probably come up with the correct answer, and this method actually works well for a lot of questions of the MCAT.
 
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