Blueprint MCAT Full-Length 1: Passage 7 — Neurotoxins

Session 191

We’re on to passage 7 in Blueprint MCAT full-length 1. Today, we’re investigating disulfide bridges, chirality, stoichiometry, confidence intervals, and more!

We’re joined by Phil from Blueprint MCAT, formerly Next Step Test Prep. 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.

[04:04] Passage 7 (Questions 35-39)

Lathyrism is one of the oldest known neurotoxic diseases and results from excessive consumption of the chickling pea Lathyrus sativus. The disease is primarily restricted to India, Bangladesh, and Ethiopia and is relatively common in communities suffering from poverty and malnutrition where a few other food options are available.

While sativus has been shown to contain the neurotoxic amino acid β-N-oxalyl-l-α,β-diaminopropionic acid or β-ODAP which is suspected to induce neurotoxic effects by serving as a structural analog of glutamate, the major excitatory neurotransmitter of the central nervous system.

Note: Amino acids are the single highest yield thing on test day so you have to care a ton about that. And then we’re also talking about neuro stuff – neurotransmitters and glutamate, which is double duty as both that neurotransmitter and an amino acid. It’s important to know that those are not mutually exclusive. So it’s both an amino acid and a neurotransmitter.

Figure 1 (Structures of glutamate and β-ODAP provided)

A group of scientists in India hypothesized that sulfur-containing amino acids have protective effects against β-ODAP toxicity after observing that populations with sulfur-deficient diets appear to be predisposed to more severe neurologic degradation after eating L. sativus.

To investigate the physiologic response to β-ODAP consumption, the researchers brought in three healthy volunteers where diets were considered to be rich in sulfur. The volunteers were instructed to fast for 12 hours and then given 150 grams of cooked L. sativus seeds to eat.

The volunteers’ plasma concentrations of methionine were recorded every hour. After 10 hours, the volunteers were provided a meal with several whole eggs, which each contains approximately 400 milligrams of methionine per 100 grams of weight. Three more hourly measurements were recorded as well as a measurement at time equals 24 hours. The results of their study can be found in Figure 2.

Figure 2 (Timeframe)

Note: You can potentially extrapolate from Figure 2 that if you’re having these L. sativus seeds everyday and not replacing with methionine, methionine is going to go down and down. This is not going to be good. It’s the same for all of these confidence intervals, which means that it is possible that from 6 hours to 25 hours, it could have stayed the same, or could have even gone down. So we know that number is somewhere in that confidence interval, but we don’t know where it is.

[10:08] Question 35

Lathyrism is known to target and degrade collagen in the lower limbs. Which pair of amino acids would best provide disulfide links to stabilize the folded form of collagen?

(A) C (Cysteine)

(B) M (Methionine)

(D) S and S

Thought Process:

This is where you need to know your amino acids inside and out. You need to know the single letter, the three-digit letter, and everything!

Serine is a trap because they’re asking about disulfide linkages. And you think S is sulfur. But serine just has an alcohol group in it and it doesn’t have a sulfur in it.

C and M both have sulfurs in them. Methionine has a sulfur and then a methyl group, which is just like a carbon sticking off of it. The cysteine has a thiol which is a sulfur with a hydrogen.

An alcohol would be OH and a thiol would be a sulfur version. So instead of the oxygen, it’s a sulfur. And also a thioether, which is just like an ether, only it’s a sulfur instead of the oxygen.

Takeaway: You’ve got to know these amino acids forwards, backward, sideways. And you got to know that the only amino acids that can do disulfide bridges are cysteines. And so the answer is just going to be Cysteine from this point.

[12:51] When Answering Pseudo-Discrete Questions

If timing is your issue, it may be an acceptable strategy to go straight to the question and not read the passage in the sciences. Because there are questions that you need to know from outside. However, if you have the time, there are going to be some questions that you do have to get from the passage. And so just completely skipping the passage is not something Phil would endorse. That’s definitely not a way to get a 528.

[14:41] Question 36

Which of the following correctly identifies a chiral center in β-ODAP?

(For answer choices, please refer to the handout.)

Thought Process:

Chiral center is where you have like the left and right, where things are like mirror image. And it also has to be something that is capable of having a mirror image, and being a different molecule like switching from the R to the S. So it’s going to have to be a carbon that’s attached to four different groups. Because if it’s attached to just three things, that’s not a word, like two of the things are the same, then it’s not gonna be a chiral center.

Also, note that the only reason you would ever show a dash or wedges if it’s important, if it’s coming towards you or away from you, which means it’s a chiral center.

Answer choice A is that carbon is connected to three things because one of them is a double bond. D is connected to four things but two of them are hydrogens. So eliminate A and D. C is glutamate, which is an outlier here, so eliminate that as well.

[19:12] Question 37

The meal the scientist provided to each of the volunteers at time 10 hours contained five eggs weighing 50 grams each, approximately how much methionine was served to each volunteer?

(A) 10 mg

(B) 1000 mg

(D) 62,500 mg

Thought Process:

So 10 hours, so time equals 10. I don’t think that time really matters. We are told that each egg contains 400 milligrams per 100 grams of weight. So that’s in the passage. So five eggs is two 250 grams of an egg. And so we would take the 400 times 2.5 and end up with about 1000. Hence, the correct answer is B.

[20:50] Question 38

The data presented in Figure 2 most strongly supports which conclusion:

(A) β-ODAP effects on plasma methionine levels are strongest at the T=2 to T=3 hour mark.

(B) The sulfur-rich meal demonstrated no significant effect on elevating plasma methionine levels to baseline.

(D) The active compound and L. sativus seeds has a biological half-life of one hour.

Thought Process:

We can eliminate A because the drop continues for a while. We never get back to baseline anywhere in the figure. And so we’re not certain that it’s weaker at four hours or five hours because it’s still low. It’s really low at two to three hours and then if it starts to creep up after that, and then you’d see these seeds are dropping this. The L. sativus is going away and the methionine levels are creeping back up.

But with the meal full of methionine, that didn’t really elevate our methionine levels that much. So we can’t say that its strongest effect was that the two to three hours because it seems like we’re still having an effect a day later. We’re never getting back to that same level.

This is the same reason you also want to eliminate D because we have no idea what the half-life is on this. They don’t give us any information.

So which kind of takes us down to B and C.

The tricky bit here is these confidence intervals. So going from Hour 6 to Hour 25, it could have actually dropped in that window because of the way the confidence intervals are set up.

Hour 6 looks like it’s somewhere between 7 hours and 13 hours. It could have been at 12 mg. And then at 25 hours, it could have been at 9 mg. And we just can’t really say anything about this. And the only thing we can say is that that seems like there wasn’t that significant of an effect because confidence intervals stay overlap. So the correct answer for this one is going to be B. The confidence interval stuff gives everyone a hard time because it looks like it goes up, it looks like it goes down by like looking at those areas and the confidence intervals. Se we can’t really make any claims about anything going on from five hours to 25 hours because none of the confidence intervals overlap.

[26:23] Question 39

The researchers originally wanted to recruit additional volunteers with sulfur-deficient diets for the study. What is the most likely reason this request was refused?

(A) It’s difficult to find patients with sulfur poor diets in the area this study was conducted.

(B) The researchers found many willing participants who had sulfur-rich diets and it therefore seemed appropriate for that to be the focus.

(D) The health risks of providing service to sulfur-deficient patients were too high.

Thought Process:

The obvious answer here is D. L-sativus makes your levels of methionine drop. The levels of sulfur-containing amino acids drop. If you’re already low, that’s going to be a more severe problem.