Blueprint Diagnostic C/P Passage 3

Session 264

Today, we go over the third passage in the Chem/Phys section of Blueprint’s Diagnostic exam. 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.

[01:46] Realizing MCAT Mistakes

'As soon as you get started, don't just assume you have to go through everything with the same amount of dedication to each and every single topic.'Click To Tweet

Pooja points out that we all have our own strengths and weaknesses. And so, the time you need to know the information should be proportional to your weakness in that material. She also adds that Psychology is one of the most neglected topics because people think it’s easy but that’s a quarter of your test. And that’s a lot of material to just shave off to the end.

[03:05] Passage 3 (Questions 14 – 18)

β-lactam antibiotics like penicillin are derived from fungi which use the molecules to defend against environmentally-borne diseases. Once discovered, these antimicrobial agents were quickly employed by physicians to treat pathogens which invade humans. These molecules are typically formed via intramolecular attack within an amino acid and secondary reactions between amino acids. The lactam designation refers to the cyclic amide ring found in the molecule. Penicillin-like drugs are analogues of amino acid residues located on bacterial cell walls. The structural similarity between β-lactam antibiotics and these residues facilitates their binding to the active site in the machinery required to build the peptidoglycan wall.

Figure 1 Molecular structure of penicillin; the R group can be variable

Notes:

In a lot of Chem/Phys passages, they’ll throw in a lot of bio/biochem-relevant passages. Hence, it’s going to be tempting to spend a lot of attention on antimicrobial agents or the potential immune function. But because we’re in the Chem/Phys section, you want to look at this passage through a Chem/Phys lens.

Highlight the things that are MCAT relevant for the Chem/Phys section. Pay attention to specific terms being introduced, like β-lactam antibiotics, intermolecular attack, and structural similarity.

In looking at the figure, spending a lot of time trying to dive into what’s particularly present isn’t a good use of your time because you don’t even know what the MCAT is going to ask about it.

[05:35] Paragraph 2

These β-lactam molecules are particularly reactive due in part to significant ring strain. Nearby nucleophiles can be acylated by the ring, allowing the ring to open. The antimicrobial efficacy of penicillin lies in its ability to acylate serine residues on enzymes that bacteria require for normal cell wall production. During the acylation of serine, the amide on penicillin is converted to an ester. This causes binding and locking of the molecules, which prevents serine from activating the cell wall-synthesizing enzymes. An intact cell wall is necessary for bacteria to stay alive.

Figure 2 Molecular structure of the amino acid serine

Notes:

Here, we get some more information but we want to stay rooted in those MCAT hot topics. Pay attention to “reactive due to significant ring strain” because understanding the relationship of reactivity and how general compounds work in terms of reactions is MCAT-relevant.

Understanding the relationship between reactivity and how general compounds work in terms of reactions is MCAT-relevant. Also, pay a lot of attention to the idea of the acylation of serine residues and that we’re converting an amide to an ester.

There’s going to be a lot of material that shows up on passages that you’re not going to be intimately familiar with and that’s half of the battle.

“The MCAT is half testing the MCAT and then half psychological. So be okay with not knowing half of the material.”Click To Tweet

This comes up a ton in the CARS section for ESL students. Students get so caught up in a definition they don’t know in their natural language. But if you don’t know it, then just skip it.

[09:49] Question 14

At which nucleophilic site is serine most likely to be acylated by penicillin?

A.Side chain OH

B.Carbonyl carbon

C.Carbonyl OH

D.Alpha carbon

Thought Process:

Draw your attention to Figure 2 which shows you the molecular structure of the amino acid serine.

One of the things Pooja recommends to students is to look at questions and translate them into actionable tasks.

For this question, which of these different components is going to be nucleophilic? Nucleophiles are defined as electron-rich species, And so, you need to pick an answer that best reflects the part of the serine that is electron-rich.

In that light, we can actually eliminate B and D, because carbons aren’t really electron-rich. They can’t be nucleophiles.

Now, A and C are both talking about OH. And you need to distinguish the key difference between A and C, where C has a carbonyl near it, whereas A is just by itself. To answer this, think about what nucleophiles do in general, which is they attack electrophiles.

And so, for something to be better at attacking, and in order to be a better nucleophile, it’s probably going to have to be something that isn’t very hindered. It has to be something that can fit in a lot of spaces, and do that attacking without much stuff in the way. And so, between A and C, A is going to be the answer because that carbonyl in C is going to get in the way.

Correct Answer: A

[14:15] Question 15

Early research into the mechanism of antibiotics theorized that it was implausible that the amide in penicillin would convert to an ester. Which of the following explains this doubt?

A.Amides possess better leaving groups than esters.

B.Esters possess poorer leaving groups than amides.

C.Amides are less reactive than esters.

D.Serine contains no good nucleophiles.

Thought Process:

In terms of our carboxylic acid derivatives, the big thing to know about them is their relative reactivity. You can either memorize the order. Or you can think about the leaving groups that are there and know that you’re not going to move from a bad leaving group to a good one.

Amide has one of the worst-leaving groups, while acyl halide has one of the best-leaving groups. And so, the deduction strategy is helpful in answering this question.

Correct Answer: C

[18:08] Question 16

Which of the following must be true if the penicillin-serine reaction “locks” in the ester formation as described in the passage?

A.The thermodynamic cost of breaking the penicillin-serine ester is larger than the thermodynamic release of amide formation.

B.The thermodynamic release of forming an amide is equal to the thermodynamic cost of forming an ester.

C.The thermodynamic cost of breaking the penicillin-serine ester is smaller than the thermodynamic release of amide formation.

D.The thermodynamic release of forming the penicillin cyclic amide is larger than the thermodynamic release of breaking the penicillin-serine ester.

Thought Process:

B doesn’t make sense because if things are equal, then they bounce back and forth. A and C are completely opposite so it’s got to be either of the two. Answer choice A makes sense here because when the energy to create is smaller than the energy to go back, then that signals it’s locked.

'If you're stuck between two answer choices, the big thing to do is look at the difference between the two of them.'Click To Tweet

This question exemplifies the general thermodynamic principle of what’s favorable, which is the idea of minimizing cost and maximizing gain. And if you have no idea where to go to the things that are the opposite. That’s not always the case every time because there are situations where there are opposites, but they’re not related to the question. But if you have no clue at all, stick to the two that are the opposite and go from there.

Correct Answer: A

[23:01] Question 17

Which functional group is NOT found on penicillin?

A.Amide

B.Imine

C.Carboxylic acid

D.Thioether

Thought Process:

Thioether is that part of the compound that has sulfur in it. Ether is just oxygen that’s between two carbons. So the sulfur is a thioether because it’s the same thing but with sulfur instead of oxygen.

Again, if you find a question confusing, try to translate it to figure out where in the passage you need to go. This is very reliant on your ability to have an effective read the first time. It doesn’t mean you have to understand everything and anything included in a passage. But you understand what key hot topics are showing up and where you can go in the passage if things are being asked about.

Right off the bat, we can eliminate A and C knowing that amide and carboxylic acids are part of penicillin as shown in Figure 1. Imine is a double bond with nitrogen and so this is the correct answer here.

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Correct Answer: B

[26:43] Question 18

On the penicillin heteroatom ring, what is the absolute configuration of the carbon labeled 1?

A.+

B.-

C.S

D.R

Thought Process:

The absolute configuration of a compound is more so referring to the orientation of different substituents in space. For instance, if you have a carbon with foreign things attached to it, where are those things in relation to each other? It’s called absolute because no matter how you rotate the specific compound in question, that’s not going to change. You can’t change it unless you’re literally breaking a bond.

Now, the absolute configuration can only be R and S. Hence, we can then cross out answer choices A and B. Then we take the next steps to figure out which of the other two choices is the correct answer.

Figuring Out the Configuration

First, identify the four substituents that are bonded to that carbon. In this case, we have nitrogen, a carboxylic acid, a carbon bonded to a sulfur, a carbon bonded to two other carbons, and our hydrogen, which hasn’t been drawn in the figure. Remember that if hydrogen hasn’t been drawn in, that doesn’t necessarily mean that it’s not there. In this case, those are the four substituents.

The second step is to identify the priorities of those substituents and assign them in relation to the atomic number. The higher the atomic number, the higher the priority. Nitrogen is going to be the highest priority because of its atomic number, and hydrogen is going to be our lowest because of its atomic number.

It gets a little tricky in situations where you have two carbons because you need to go one bond away and compare to what’s going on there. One of our carbons is bonded to sulfur, but our other carbon is only bonded to two other carbons.

Hence, you need to look at the one bonded to the sulfur. Then the carbon on our dash is going to be priority group number three.

Look at the Order

In terms of our order, we have one, two, and three. And from there, you just need to count from one to two to three and determine the direction you move in, whether it’s clockwise or counterclockwise. You can imagine yourself drawing like a little arrow or moving your finger in that direction. So it’s supposed to be in the clockwise direction which is the R configuration.

Note, however, that the hydrogen is not on a dash and the carboxylic acid group is on our dash. Our hydrogen is racing towards us. Because of that, we need to reverse the configuration that we’ve assigned so it moves along the counter-clockwise which is the S configuration.

Correct Answer: C