AAMC The Official MCAT Practice Question #2 biochem section

[m25]

Which steps involved in the contraction of a skeletal muscle require binding and/or hydrolysis of ATP?

1. I. Dissociation of myosin head from actin filament
2. II. Attachment of myosin head to actin filament
3. III. Conformational change that moves actin and myosin filaments relative to one another
4. IV. Binding of troponin to actin filament
5. V. Release of calcium from the sarcoplasmic reticulum
6. VI. Reuptake of calcium into the sarcoplasm

Answer: I, III, and VI only
Explanation: Dissociation of the myosin head from the actin filament requires the binding of ATP (I). Attachment of the myosin head to the actin filament requires calcium and a troponin/tropomyosin shift (II). The conformational changes that move actin and myosin relative to one another require that ATP be hydrolyzed, for these changes occur upon release of the products of hydrolysis (ADP and Pi) by the myosin head (III). Binding of troponin to actin does not require the hydrolysis of ATP (IV). Release of calcium from the sarcoplasmic reticulum also does not require ATP hydrolysis. This release occurs when calcium ions move via voltage-gated ion channels down their concentration gradient (V). The reuptake of calcium into the sarcoplasmic reticulum occurs via an ATP-hydrolyzing pump that moves calcium against its concentration gradient (VI). Thus, C is the correct response.

How does III require binding and/or hydrolysis of ATP? I'm guessing the "Conformational change that moves actin and myosin filaments relative to one another" refers to the power stroke step, but according to the diagram below and in the answer explanation, ATP binding nor hydrolysis is needed during power stroke. The only thing that happens in this step is that already hydrolyzed ADP and Pi is released, How is this statement correct? How does the release of already hydrolyzed ADP and Pi qualify as "requiring binding and/or hydrolysis of ATP"?

PS I hope I labeled the title correctly, I've tried contacting modulators about making new threads to discuss the new AAMC practice materials but haven't gotten a response yet, but it seems like it's okay to ask here as long as I make it clear in the title that it's from AAMC official practice questions. Please let me know if I've done anything incorrectly and I will fix/delete accordingly.

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[NextStepTutor_1]

It seems they're taking a broad-stroke approach to this problem. While I agree with you that the actual power-stroke event occurs when ADP + Pi are released, this can only happen when ATP was bound to the myosin head and subsequently hydrolyzed. So in all intents and purpose, the power stroke is dependent on the attachment and hydrolysis of ATP, albeit somewhat indirectly.

Now, that leads us to the task of internalizing this mode of thinking and looking back at the answer choices. In this general framework of choosing anything that could be a product or event, occurring immediately or not from the actual binding/hydrolysis of ATP, only II sees enticing. However! ATP binding allows the head to be cocked, but, as the explanation states, it's not ATP that allows it bind - instead, it's calcium and it's role in removing the troponin/tropomyosin complex.

And lastly, how could you have gotten this right? A good lesson from this question and a motto I work by when attacking MCAT questions is to start very general. Don't restrict your way of thinking to one particular area without consulting the question and answer choices with an open mind.

Cheers!

 

[m25]

It seems they're taking a broad-stroke approach to this problem. While I agree with you that the actual power-stroke event occurs when ADP + Pi are released, this can only happen when ATP was bound to the myosin head and subsequently hydrolyzed. So in all intents and purpose, the power stroke is dependent on the attachment and hydrolysis of ATP, albeit somewhat indirectly.

Now, that leads us to the task of internalizing this mode of thinking and looking back at the answer choices. In this general framework of choosing anything that could be a product or event, occurring immediately or not from the actual binding/hydrolysis of ATP, only II sees enticing. However! ATP binding allows the head to be cocked, but, as the explanation states, it's not ATP that allows it bind - instead, it's calcium and it's role in removing the troponin/tropomyosin complex.

And lastly, how could you have gotten this right? A good lesson from this question and a motto I work by when attacking MCAT questions is to start very general. Don't restrict your way of thinking to one particular area without consulting the question and answer choices with an open mind.

Cheers!

Thank you! I will try to think in more general terms for future MCAT questions!!

 

[Prometheus123]

I published this post as a blog article about this question. See the post for the full details, references, figures, etc.

I believe the "correct" answer to this question is simply wrong. The answer should be I, II, and VI.

Here is a quote from an article about sliding filament theory published in the journal Nature:

"Two key aspects of myosin-actin cycling use the energy made available by the hydrolysis of ATP. First, the action of the reaching myosin head uses the energy released after the ATP molecule is broken into ADP and phosphate. Myosin binds actin in this extended conformation."

In other words, ATP hydrolysis is required for myosin to bind to actin. II is a true statement. Yes, Ca2+ must also bind to troponin and move tropomyosin out of the way, but that alone is not sufficient. ATP hydrolysis is also required.

III is also wrong but is a bit more debatable. From the same Nature article:

"Second, the release of the phosphate empowers the contraction of the myosin region [power stroke]."

The conformation change that moves actin and myosin filaments relative to one another, called the power stroke, is caused by myosin releasing ADP and inorganic phosphate. Did ATP hydrolysis have to happen at some point prior to this? Yes. Is it the mechanism that directly causes the power stroke? No.

Interestingly, it would be easy to make this mistake if the person who wrote this question only referenced this figure in the Wikipedia article about the sliding filament theory. The figure does seem to mix up the order of the steps. Just goes to show that if your job is to write official MCAT questions, you shouldn't use Wikipedia as your only source of information. We students are held to that standard, so why not the AAMC?

My concern is that if AAMC's practice materials contain such glaring errors and fundamental misunderstandings of basic science principles, the MCAT itself is also likely to contain similar errors. And no one ever sees their MCAT and which questions they got wrong after they take it, right? So how would we ever know if a few of the questions we got wrong were actually incorrect questions based on incorrect Wikipedia figures instead of actual scientific sources? Where is the accountability?