Blueprint MCAT Full-Length 1: Bio/Biochem 8 –Beta-oxidation

Session 220

We are back with another Bio/Biochem passage! Alex and I discussed mini-breaks between passages to clear your mind for the next passage.

We’re joined by Alex 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.

[02:00] What to Do In Between Passages

“There's a very particular kind of MCAT information processing fatigue that happens when you're feeding all of these passages into your mind.”Click To Tweet

Alex recommends that in between every passage, sit back in the chair, and let your eyes focus on a distant corner of the room. And take five seconds to mentally disengage from whatever you’ve read.

Clear the memory buffer and then engage again with the next passage. And Alex has found this to be immensely helpful to clear the decks.

[03:57] Passage 8 (Questions 40 – 43)

Paragraph 1

Beta oxidation is a process that converts fatty acids into acetyl-CoA groups that can enter the Krebs cycle. This process occurs in the mitochondria. In humans, the normal fatty acids we eat are too big to passively pass through the inner mitochondrial membrane. An acyl-CoA molecule must first be transformed into an acyl-carnitine molecule in order to enter the mitochondrial matrix via a translocase protein. That conversion is catalyzed by carnitine palmitoyltransferase I, whose mechanism is thought to involve a histidine residue that activates the hydroxyl group on carnitine. Once inside the mitochondrion, the acyl-carnitine is converted back into an acyl-CoA molecule.

Alex’s Notes:

Take a step back and ask yourself what the paragraph is saying or describing, and its purpose. Things to highlight are in bold above.

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When reading a passage, Alex recommends interpreting what it means and then comparing their notes to the key terms and the outline that Blueprint gives you. And over time, you get better at correlating one with the other.

And so, the key takeaway from this paragraph is that there’s this process called beta oxidation. It converts fatty acids into acetyl-CoA because fatty acids themselves are too big to go into the mitochondria. They can’t squeeze through that membrane. And in order to do that, acyl-CoA must first be transformed into this new molecule, acyl-carnitine.

Then right below the passage, we have Figure 1, which is the structure of carnitine. And this is presumably what gets modified. This is the vehicle by which those acyl groups are shuffled into the micro into the mitochondria.

Looking at the figure, you could see a structure and it’s a molecule and it’s got some atoms in it. But we don’t really need to analyze it any more than that unless we get a specific question about it.

And then below, in Figure 2, we have a structure of palmitic acid, which is a generic fatty acid. You’ve got that carboxylic acid group, and then a big long chain of carbons.

[08:30] Paragraphs 2-3

Acylcarnitine translocase deficiency is an autosomal recessive disorder characterized by malfunction of the translocase whose normal function is to exchange acylcarnitine from outside the mitochondrion for carnitine inside the mitochondrion.

In the metabolism of a molecule of palmitic acid, once converted to palmitic acyl-CoA and having entered the mitochondrial matrix, four steps will occur and be repeated until the entire molecule is converted to 8 acetyl-CoA molecules. The first three steps are outlined in Figure 3.

Alex’s Notes:

So we know how the process works normally. And now here’s acetylcarnitine translocase deficiency, which is this recessive disorder where the process breaks. This is common on the MCAT when they parlay that into saying what would you expect to happen in these patients.

Based on your outside knowledge of how energy metabolism works, what predictions can we start making about how this might affect someone’s broader physiology?

What we can predict here is that the translocase breaks, which means it can’t exchange acyl-carnitine from outside for the carnitine inside. And then we have some information about the metabolism of a molecule of palmitic acid. And then we get Figure 3, which details those steps.

We don’t really know if the above two paragraphs are important. But we know there’s a deficiency or a malfunction. In this case, pluck out the bones of the process, which in this case is the translocase malfunctions, and it can’t exchange these carnitine molecules. And then this paragraph talks about how palmitic acid is metabolized.

The whole thing’s converted to acetyl-CoA molecules. You don’t have to dig in any more than that until maybe a question asks us to interrogate this process in more detail.

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Figure 3 shows the first three steps of the beta oxidation of palmitic acid. This should be a process that students are hopefully familiar with because the process of oxidation is included in the MCAT content categories.

[12:37] Paragraph 4

Step 1 produces an FADH2 and step 3 produces an NADH + H+. Table 3 shows how many ATP are produced per NADH, FADH2, and per acetyl-CoA.

Alex’s Notes:

This paragraph is providing a link now between the figure above and the table below. We have a list of steps on how fatty acids are metabolized. And then below, we have a table that gives us more data. How much ATP do we get per process?

[13:32] Question 40

If we start with the molecule below instead of palmitic acid, which step will be interrupted and which enzyme will be used to correct the issue?

Step 1, phosphatase
Step 1, isomerase
Step 2, reductase
Step 2, kinase

Thought Process:

This is like a classic two-by-two question where we have two nuggets of information in each answer choice we have. Given the choices, immediately, the only options for which step it could be is Step 1 or Step 2. We could ignore Step 3 for now because it can’t possibly be right.

Start with evaluating the first chunk of the question – so is Step 1 or Step 2? And if we look at these steps, which molecule does it resemble the most? It’s almost the same molecule, it’s just in a different spot.

Enzymes are very specific to the molecule that they bind to, and if it’s not shaped in the right way, then it’ll probably interrupt the process. If Alex had to guess, that’s probably the concept that this question is trying to interrogate.

If Step 1 takes this clean, beautiful, double bond free carbon chain and converts it into one with a double bond in it, and if we had a fatty acid molecule with a double bond, it would interfere with Step 1. Because that enzyme that does that conversion, presumably, is looking for a clean, single bond only carbon chain. And we’re giving it to a carbon chain that already has a big fat double bond right in the middle.

And so, Step 1 is the right answer here, which is the process that it interrupts. In which case, we can eliminate C and D.

And what’s left now is to ask what enzyme are we looking for? What will convert this molecule with a double bond in the middle to that second molecule on the left that has a double bond much closer to the right? And what classes of enzymes do we normally look for, which rearrange bonds?

Phosphatases remove phosphates from molecules. Kinases add phosphate groups and phosphatases remove phosphate groups. In this case, A is not the right answer because there’s no phosphate that’s being added or removed.

Correct Answer: B

[18:26] Question 41

Injection of insulin into the bloodstream is LEAST likely to result in which of the following?

Increased glycogen synthesis
Decreased lipid synthesis
Increased esterification of fatty acids
Decreased gluconeogenesis

Thought Process:

Obviously, it’s a pseudo discrete question because they never mentioned insulin in the passage. It’s related to metabolism so there must be something about it in the passage. Now, the MCAT loves doing this. They throw you a pseudo discrete after they’ve just had you digging around in the passage.

Most students understand insulin’s job right is to get glucose into cells so we can use it.

A – Glycogen is a storage molecule. And we’re storing glucose and that happens when we get glucose into the cell. That’s going to happen. Therefore, this is not the right answer because we’re looking for the LEAST likely. We’ve got to make sure we understand the question.

D – Gluconeogenesis is making new glucose. But we don’t need to make new glucose if we are injecting insulin. We’re taking insulin so we can get it out of the bloodstream. So cross this out too.

So we cross out A and D, and we’re now down to either B or C.

B – Lipid synthesis is making fat. Well, if we have excess energy, excess sugar, or excess glucose, we’re probably going to store that as fat too. Therefore, that would be increased. So this answer choice doesn’t make sense.

C – Esterification is the formation of ester bonds. You’re linking a bunch of fatty acids together so that they can best be stored. Esterification of fatty acids is exactly what you’d expect when you inject insulin because it’s right up there with lipid synthesis. You’re taking a bunch of sugar in or you’re not burning fatty acids anymore. You’re actually linking them up for storage. So that’s exactly the process that we would expect from the injection of insulin.

Correct Answer: B

[24:39] Question 42

In which steps in Figure 3 is the fatty acid oxidized?

Step 1
Step 2

III. Step 3

I only
III only
I and III only
I, II, and III

Thought Process:

Alex thinks this is a great question where people can get really tangled in the details for a long time examining those steps and those flow charts. And if we can just scroll down a little bit, the passage tells us everything we need to know.

It says:

Step 1 produces an FADH2 and step 3 produces an NADH + H+. Table 3 shows how many ATP are produced per NADH, FADH2 and per acetyl-CoA.

In the body. FAD+ and NAD+ exist as free molecules. They float around. So if you’re ever producing an FADH2 or NADH + H+, that means they are getting reduced. You are adding hydrogens to them. Which makes sense because they are later fed into the electron transport chain. If they are getting reduced, something else is getting oxidized. And in this case, it’s the fatty acid.

But just looking at the chart, you’re increasing bonds to oxygen, that’s oxidation. And it must be one, two, and three. And this is an interesting and finer point of chemistry because when you add water across a double bond and convert it into this OH that means we’re adding one oxygen and two protons. So it means there’s no net redox at all.

If a fatty acid is being oxidized at Step 2, you would expect an evolutionary process to have optimized it but extracting energy out of it, coupling it to one of these processes. We can then eliminate Step 2 by examining that mechanism. You’re adding water, which means you have that oxygen and those two protons. But those two protons cancel out the two electrons that have been transferred. So, there’s no net redox. But we could have eliminated it down to C and D with that one sentence in that paragraph there.

Correct Answer: C

[29:47] Question 43

Which of the following is most likely NOT a symptom of acylcarnitine translocase deficiency?

Hyperglycemia
Muscle weakness
Liver damage
High ammonia levels in blood

Rewording the question:

When you get a question like this where “which of the following is most likely not?” framing really helps you conceptualize it better. And so, three of these are symptoms, and which one isn’t?

Thought Process:

It’s a translocase deficiency characterized by the malfunction of the translocase, whose normal function is to exchange acyl-carnitine from outside for carnitine inside.

This is expanded upon in the first paragraph, where it says: An acyl-CoA molecule must first be transformed into an acyl-carnitine molecule in order to enter the mitochondrial matrix. And that’s because the fatty acids that we eat are too big to passively pass through the inner membrane.

Now, as we link those two concepts together, we can infer that fatty acids are broken down into acetylcholine molecules.

We need this carnitine translocase system to get the acetyl-CoA into the mitochondria so they can be broken down for energy. And so, they can be fed into the Krebs cycle. We know that from our content review. And so, presumably, this deficiency interferes with the metabolism of fatty acids.

Prediction:

What symptoms would we see if someone can’t metabolize fatty acids?

A – We can’t break down fat. So why would we have high sugar in the blood? If we are disproportionately leaning on glucose as an energy source, why would there be loads of it hanging around?

This question is a great example where maybe you don’t want to proceed by process of elimination and it’s probably easier to get to A than it is to rule out some of the other ones which are more subtle.

D – Ammonia in the body comes from the breakdown of nitrogen-bearing molecules, mostly proteins. It makes sense here. If we can’t metabolize fatty acids, presumably we got to get energy from somewhere else, such as sugar and amino acids.

If someone’s really relying on amino acid metabolism for energy, they’ll probably have a lot of byproducts of that metabolism in their blood. So high ammonia levels fit here.

B – This is a very natural symptom of lack of energy availability.

C – Many things mess up the liver. If you can’t break down fatty acid, fat will accumulate in the liver, and eventually cause liver damage.

Correct Answer: A