Blueprint Diagnostic Chem/Phys Passage 5

Session 266

Tune in this week for an in-depth analysis of Chem/Phys passage 5. We’re joined by Pooja from Blueprint MCAT. If you would like to follow along on YouTube, go to premed.tv.

Listen to this podcast episode with the player above, or keep reading for the highlights and takeaway points.

[01:48] The Purpose of a Diagnostic Test

“Diagnostic exams, in general, are meant to find what you are weak in.” Click To Tweet

If you’re getting questions right over and over again, you’re not actually learning, you’re just reinforcing the things that you’ve already learned. You’re not adding new things to your brain and new strategies to your back pocket for when you need them.

Hence, although it’s really hard, take the diagnostic exam as a learning opportunity, no matter how brutal and painful it may feel at the time.

[03:32] Passage 5 (Questions 23 – 27)

A key modulator of action potential firing is the hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel. These channels are permeable to both Na+ and K+. The HCN current, Ih, is found in neurons under hyperpolarization of the cell membrane. Ih is proportional to the frequency of firing of action potentials.

Notes:

Notice the ion channel which is something you can highlight. Pooja recommends highlighting topics and relationships that are MCAT-relevant, such as, in this case here, “permeable” and “Ih is proportional to the frequency of firing of action potentials.”

[06:00] Paragraph 2

Neurologists wished to determine if a new drug, compound X (Figure 1) is able to block Ih and reduce neuropathic pain, providing significant analgesic effects to those with pain.

Figure 1 Structure of lidocaine (left) and compound X (right), a potential ion channel blocker

Notes:

'If you don't know what a word means, it doesn't mean you're screwed and can't answer the passage. It just means you have to rely on context.'Click To Tweet

Even if you don’t know what lidocaine or analgesic means, you can just look at the context of the passage. And you could infer from here that analgesic probably has to do with reducing pain.

Here, you could highlight compound X and block Ih as well as highlight the analgesic effect.

[08:36] Paragraph 3

Compound X’s effect on neuronal firing was first compared to lidocaine, a known sodium channel inhibitor. Ganglion cells were treated with 3 different concentrations of Compound X. Sodium current was isolated and then recorded using patch-clamping. Figure 2 shows the results of these recordings.

Figure 2 Na+ current in ganglion neurons treated with compound X; traces were recorded in the presence and absence (control) of different concentrations of compound X

Notes:

We can see the control is without any analgesic. You’re getting this firing, which means pain is being signaled, and we want less than that. And so with each decrease in dosing or a lower concentration with the one of compound X, it’s much closer to the control. Therefore, it seems like 100 of this compound X does a much better job of being an analgesic.

Pooja reminds us to note the general relationship, inserting that compound acts as an analgesic effect. And the more you add, the better it will be. And so, knowing there is some difference between the initial (one micromolar) and the control is also important to think about as well. And what this paragraph suggests is we’re testing three different concentrations on the ganglion cell.

'Knowing what's being talked about in a paragraph, especially when it's related to an experiment, can help inform what you want to highlight.'Click To Tweet

Here, we can highlight “sodium current” and “recorded.” In terms of the goals of the method, we’re looking at the effects of ganglion cells with different concentrations. So we can highlight “ganglion cells” and “concentrations of compound X.”

Pooja reminds students to not worry about time when they’re studying and struggling with the MCAT. First, make sure you understand the general structure and layout of your passages.

The MCAT is a standardized test so as you continue to read more and more passages, you’ll notice that a lot of them are more or less structured the same way.

The MCAT will provide an intro to some topics that may or may not be related to what you know in terms of MCAT knowledge. Then they’ll talk about an experiment and give you the methods and then the results.

Being able to leverage that can help because it eliminates the unknowns that you get on test day. It can help inform what you want to highlight when you get to each chunk of that standard passage structure.

[13:31] Paragraph 4

To test if compound X was indeed also a blocker of HCN channel currents, the effect of the drug on HCN currents in ganglion cell neurons was recorded. HCN channel whole-cell current in neurons was induced by giving a membrane potential step from a holding potential of -60 mV step to -140 mV for 700 ms and then back to -70 mV. Solutions of 5 mL each were prepared with differing amounts of Compound X. Figure 3 shows the concentration effect of Compound X on HCN currents in neurons.

Figure 3 Inhibition of HCN currents by addition of compound X

Notes:

Again, we’re looking at the purpose of a new experiment. Here, we can highlight “compound X was indeed also a blocker of HCN channel currents” because that’s what we’re testing to see if that’s true.

We can also highlight the “concentration effect” which will help orient us to Figure 3. The figure itself is showing inhibition by adding. There’s inhibition of currents happening and when you go from left to right, you’re adding more and more of that compound X.

[17:34] Question 23

Compound X and lidocaine can be separated using ether extraction because:

A.Lidocaine is lipophilic while compound X is hydrophilic.

B.Compound X is lipophilic while lidocaine is hydrophilic.

C.Both molecules are hydrophobic with only nonpolar groups.

D.Lidocaine is hydrophilic while compound X is hydrophobic.

Thought Process:

With this particular passage, we were told that they were compared, but we weren’t told about the results of that comparison. With a lot of things in biology, there are a lot of different ways to get to the same outcome.

B – It doesn’t make sense to rely on its functionality. It would make a little bit more sense to rely on the differences between them.

The question is why there can be a separation between compound X and lidocaine. For that reason, we need to rely more on what’s different between the two, rather than what’s the same.

Figure 1 has two different structures. One of them is Compound X and it has a ton of different charged compounds.

If we put a nonpolar solvent through a funnel that has our compound like is going to dissolve with like. And so, the nonpolar parts of our solution are going to separate from the cooler parts.

The answer relies on us understanding that one part is polar and one part is nonpolar. So when you put either in the mix, which is a nonpolar solvent, it’s going to separate. For these two reasons, A is going to be our answer.

Correct Answer: A

[23:24] Question 24

Based on the observed effects, what is the minimum dose of Compound X required to reduce the HCN current to half the normal current?

A.5 x 10-4 μmol

B.1 x 10-2 μmol

C.5 x 10-2 μmol

D.5 x 10-2 mol

Thought Process:

The information we need here is in Figure three. Pooja says that logic is important for this question. You need to combine the concentration that you get from the figure with the actual volume because the concentration is just moles per liter.

Based on dimensional analysis, all you really need to do is just find the molar, multiply it by the liters, and then you would get to your answer. And so, moles per liter times liter gives you two moles. In terms of getting to that on this figure, we just need to do a little bit more digging into the passage.

'Half of the battle of answering questions that are heavily rooted in passages is being able to understand where in the passage you need to look.'Click To Tweet

Here, the caption says “inhibition of HCN currents by addition of Compound X.” The x-axis shows the log of our X, and Y-axis shows the change. In terms of having the normal current, you want to look at the y-axis, then find where on the x-axis is our y value equal to .5.

Log base 10x would mean that it’s going to be 10 to the power of whatever your answer is. Since it’s negative five, our x or molar concentration is going to be -10-5 mol molar.

Now, you can’t just use five milliliters because the unit of molarity is moles per liter. So we need to convert our five milliliters to liters. Instead of .005, you can have 5 x 10-3 liters.

Then 10-5 x 10-3 and that would get you to 5 x 10-8 moles. Then convert 5 x 10-8 moles into μmol which gets you to 5 x 10-2 μmol.

Correct Answer: C

[30:27] Question 25

How many chiral carbons are present in compound X?

A.0

B.1

C.3

D.5

Thought Process:

First, you have to be able to know what chiral carbon is, which is carbon atoms attached to four different substituents. Looking at Figure 1, we need to find the carbons attached to four different things, which is 0.

Correct Answer: A

[34:13] Question 26

How many grams of compound X (MM = 292.81 g/mol) are required to create a 1.5 M solution of the mixture used to test HCN current as shown in Figure 3?

A.0.0075 g

B.1 g

C.2 g

D.6 g

Thought Process:

Pooja recommends that when answering this kind of question, write out what you’ve been given and what you need to find. This helps you understand what the next path is.

In this case, the given are the molar mass, the molar concentration, and the volume of our mixture. Then we need to find the grams of our compound involved.

Pooja says this is a dimensional analysis problem where you convert from unit to unit to unit to eventually get you to grams.

So 1.5 moles per liter multiplied by 5 x 10-3 liters is 7.5 x 10-3 moles. Then multiply that by our molar mass which is 292.81. You can just round it off to 300 then multiply that by 7.5. So we’re using a scientific notation that turns into 7.5 x 10-3 multiplied by 3 x 102.

One of the rules that you have to know in scientific notation is that multiplying the two is the same thing as just adding the exponents.

So negative three plus two is a negative one. Hence, we end up with 22.5 x 10-1 grams which gets us 2.

Pooja also adds that relying on rounding is important. The MCAT expects you to do that because they will give you an answer that is in line with that. They’re not going to expect you to bust out your mental calculator.

Correct Answer: C

[40:49] Question 27

What alteration to an HCN channel will reduce the transport of K+ in favor of Na+ transport?

A.Increasing the diameter of the channel by adding amino acids

B.Decreasing the diameter of the channel by removing amino acids

C.Replacing the serine groups in the channel with alanine

D.Replacing the alanine groups in the channel with serine

Thought Process:

The question is asking you about what is the difference between sodium and potassium. Both are very similar and the only difference between them is the size. Hence, the answer is going to have to be between A and B.

The fact that the HCN channel is permeable to both sodium and potassium is provided in that first paragraph. But you don’t need that to answer this question, you need to know the difference between sodium and potassium. The key difference between them is the size right where potassium is larger than sodium.

Answer choice A doesn’t make sense because if it’s a big channel that it can bring in both, there may be less wiggle room with the potassium when it goes through. But it doesn’t select one over another. Hence, B is the correct answer here.

C and D don’t make sense because the difference between serine and alanine is polarity versus non-polarity. And because sodium and potassium are so chemically similar, if you change the chemical composition of your channel, it’s going to do the same thing to both of them.

With a polar group, it’s going to allow you to bring both of those two things in. But if you’re replacing it with a nonpolar group, you’re not going to let sodium and potassium through.

Correct Answer: B

[48:56] Final Thoughts

Just because the MCAT is a brutal test does not mean you’re not smart and you can’t go to medical school.

'Numbers are a measure of something that isn't exactly correlated to what you actually know.'Click To Tweet

Ultimately, just focus on mastering the content and being able to truly understand and be able to explain it to someone else. Use whatever strategies you need to help you supplement whatever gaps you have in your content. And if you focus on that, and you improve on it, the numbers are going to follow.