Session 224

This week, we cover lipoproteins and cholesterol as we break down bio/biochem passage 10 with Adam 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.

[01:57] MCAT Tips & Tricks

One of the techniques Adam loves to use when attacking passages is to take it paragraph by paragraph. A lot of people fall into the trap of over highlighting or picking out minor details because they try to pick out the important pieces as they’re going.

When you read a paragraph, take about five seconds to do mental accounting, see what were the important tidbits, distill out the main idea, and then move on to the next paragraph.

[02:56] Passage 10 (Questions 53 – 56)

Elevated low-density lipoprotein (LDL)-cholesterol is a risk factor for both Alzheimer’s disease (AD) and cardiovascular disease (CVD), suggesting a common lipid-sensitive step in their pathogenesis. Previous results show that AD and CVD also share a cell cycle defect: chromosome instability and up to 30% aneuploidy in neurons in AD and in smooth muscle cells in atherosclerotic plaque in CVD. Specific degeneration of aneuploid neurons accounts for 90% of neuronal loss in the AD brain, indicating that aneuploidy underlies AD neurodegeneration. Mouse models of AD develop similar aneuploidy through amyloid-beta (Aß) inhibition of specific motor proteins and consequent disruption of mitotic spindles.

Notes: 

This is a pretty dense passage which can be a little scary, but then again, let’s just try to boil this down to some important pieces. Keywords or key phrases we think are worth highlighting are highlighted in bold.

One of the reasons students get overwhelmed is that the passages can differ so widely. And the switch up can be enough to turn you off. So if that’s something that you’re noticing, just take three seconds, close your eyes, reset, acknowledge it’s in the past and move forward.

[06:42] Paragraph 2

Researchers aimed to investigate whether lipoproteins and cholesterol induce chromosomal mis-segregation. First, metaphase chromosome analysis and fluorescence in situ DNA hybridization (FISH) were used to determine the level of trisomy 16 in the spleen cells of mice fed a high-cholesterol diet (HCD) relative to mice fed regular chow (RC). Results are shown in Figure 1.

Figure 1 Percent of splenic cells demonstrating trisomy 16 in mice fed regular chow (RC) or a high-cholesterol diet (HCD)

Notes: 

Looking at the figure, we see the comparison between regular chow and the high cholesterol diet mice. The difference represented in the percentage of trisomy 16 here. It’s significant because we see this P value represented here as point 02, which is less than the standard value of .05 which designates our significance.

[08:05] Paragraph 3

Then, to establish that lipoproteins and cholesterol were directly responsible for the aneuploidy observed in cholesterol-fed mice, researchers analyzed the chromosomes of human telomerase reverse transcriptase (hTERT) cells in culture after exposure to various lipids. Actively growing hTERT cells were treated with 20 μg/mL of LDL, oxidized LDL (OX-LDL), or high-density lipoprotein (HDL) for 48 hours, then arrested in metaphase and stained to reveal levels of trisomies 12 and 21 (Figure 2).

Figure 2 Levels of trisomy 12 and 21 in lipid-treated hTERT cells

Notes: 

We have another experimental setup here, this time with hTERT and exposure to different lipids and then we’re seeing how that affects the percentage of trisomies either 12 or 21.

[09:04] Paragraph 4

Finally, researchers tested the effect of ethanol (EtOH) on levels of trisomy 21 in OX-LDL, LDL, and HDL-treated hTERT cells (Figure 3).

Figure 3 Levels of trisomy 21 in hTERT cells incubated with lipoproteins alone or with lipoproteins and ethanol (EtOH)

Notes: 

We see that the addition of ethanol is actually reducing the amount of trisomy 21 that we’re seeing in those LDL species, though not with HDL.

[11:41] Question 53

In cells with elevated low-density lipoprotein levels, ethanol has been shown to act directly on these lipoprotein molecules in a way that decreases their trisomy-inducing effects. On the basis of this information, compared with untreated hTERT cells, hTERT cells incubated with ethanol alone would most likely:

21. have a higher probability of displaying trisomy 21.
22. have a lower probability of displaying trisomy 21.
23. have a similar probability of displaying trisomy 21.
24. have a higher probability of displaying trisomy 21 than hTERT cells incubated with HDL and ethanol.

Thought Process:

A & D – A higher probability doesn’t make sense because why would ethanol, all of a sudden, be higher when all of these are lower. The addition of ethanol only is only decreasing the probability that we see in this in Figure 3. and so, we can eliminate A and D because they don’t match the trend that we get here.

But now, all we see in figure three is that the addition of ethanol is decreasing dryzone probability when we’re working with LDL. So we can’t necessarily say that it’s going to have the same effect with the hTERT. The HDL has no effect. There’s no statistical significance between these values here.

hTERT is the base value of percent of trisomy and we don’t know that ethanol is going to have an effect in untreated hTERT cells. Because we only see the effect with the LDLs and not with HDL. So we can’t assume that ethanol is going to have a diminishing effect. So the ethanol is countering the action of the LDL, rather than doing something directly itself. Therefore, the correct answer is C.

Correct Answer: C

[21:13] Question 54

Paragraph 1 mentions that aneuploidy in Alzheimer’s disease may result from disruption of the mitotic spindle. This apparatus is composed of what structures?

1. Microfilaments
2. Intermediate filaments
3. Microtubules
4. Myosin filaments

Thought Process:

C – The mitotic spindle is composed of microtubules, the cytoskeletal components made of tubulin.

B – Intermediate filaments are structural elements that play a role in cell adhesion.

A and D – The microfilaments and myosin are related to muscle and muscle contraction.

Correct Answer: C

[22:59] Question 55

High levels of LDL and OX-LDL increase the proportion of cholesterol in cell membranes. If the trisomy 21 data in Figure 2 can be attributed to the effect of cholesterol on these membranes, which of the following statements is most likely true?

1. hTERT cells treated with OX-LDL display more rigid membranes than hTERT cells treated with LDL.
2. Untreated hTERT cells display more rigid membranes than hTERT cells treated with LDL.
3. At moderate to high temperatures, ethanol increases membrane fluidity.
4. hTERT cells simultaneously exposed to HDL and LDL display increased membrane fluidity relative to untreated cells.

Thought Process:

At physiological temperatures, cholesterol makes membranes more rigid. From there, it’s a lot easier to adjudicate between the answers.

A – We don’t really see any significant difference between the OX-LDL and LDL values here. So for that reason, we throw out A.

B – This is the exact opposite of this tidbit that we’re given in the question stem here where it’s telling us that more LDL increases cholesterol making the cell membranes more rigid. So we throw out B because it’s opposite of the conclusion they’re telling us here.

C – We know that ethanol when added to those LDLs, decreases the effect of LDL. So it dropped that percentage of trisomy. And so, if the increase in trisomy that LDL showed us was due to increasing membrane fluidity, we know that ethanol counters that activity. And so, C does make sense. Because at moderate high temperatures, which is our physiological temperature, ethanol increases membrane fluidity. It’s the opposite of what LDL is doing for us. And so, it makes sense if ethanol is doing the opposite of what the LDL is doing.

The LDL is increasing membrane fluidity, which gives us a higher percentage of trisomy 21. But the ethanol, on the other hand, is increasing the membrane fluidity and counteracting it.

D – We don’t have that data so we can cross out D.

Correct Answer: C

[34:56] Question 56

OX-LDL most likely forms through the reaction of LDL with:

1. free radicals.
2. FADH2 and NADH.
3. hydrogen gas.
4. saturated fatty acid tails.

Thought Process:

The key to answering this question is recognizing the difference between LDL and OX-LDL. And of course, it’s the fact that OX-LDL is oxidized.

So in these answer options, we’re looking for which one is going to be capable of oxidizing LDL. And the only oxidizing agent here is free radicals.

Correct Answer: A

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