Friday, September 13, 2013

Better Biochemistry: Teaching ATP Hydrolysis for the MCAT

I'm digesting the idea that many American biochemistry courses teach to the MCAT exam [see Better Biochemistry: Teaching to the MCAT?]. What this means is that the scientists who teach biochemistry are willing to let the curriculum be established by a group of American medical schools (AAMC). That organization has put up a website to guide faculty members and students in preparation for the 2015 MCAT exam [MCAT2015: Biological and Biochemical Foundations of Living Systems].

One of the links takes you to a chemwiki at the University of California, Davis: Biological Chemistry. From there you can click on several topics. I picked ATP/ADP to see what kind of information the MCAT thinks is appropriate. The information on the ATP website is provided by Tiffany Lui of the University of California, Davis so it's not something that AAMC created. Nevertheless, it is presumably indicative of the sort of thing that might appear on the MCAT exam.

According to this website, "Breaking one phosphoanhydride bond releases 7.3 kcal/mol of energy." This statement is accompanied by a diagram of chemical reactions ...

It's strange that the conclusion is reported in kcal/mol when the actual values are shown in kJ/mol. However it's easy to do the conversion since 1 cal is equal to 4.184 joules. Thus, 7.3 kcal equals 30.5 kJ and that corresponds to the standard Gibbs free energy change of the first reaction. Based on that reaction, it's fair to say that the hydrolysis of ATP to ADP + Pi releases 30.5 kJ/mol of energy under standard conditions.

On the other hand, it's not accurate to say that "breaking one phosphoanhydride bond" always produces the same amount of energy. Most textbooks have tables like the one show here (upper left). It shows that the standard Gibbs free energy change is -45 kJ/mol for the hydrolysis of ATP to AMP + PPi (pyrophosphate). That's much more than 30 kJ/mol.


Better Biochemistry
Furthermore, most modern textbooks point out that the actual usable Gibbs free energy change for ATP hydrolysis inside the cell is actually much higher than the standard Gibbs free energy value. Most textbooks take students through the calculation based on the known concentrations of ATP, ADP, and Pi in liver cells. The Gibbs free energy change under those in vivo conditions is about -48 kJ/mol.

One of the most important concepts in modern biochemistry is that standard Gibbs free energy changes don't tell you a damn thing about whether a reaction is going to proceed inside a cell. That because most biochemical reactions are near-equilibrium reactions where ΔG = 0. When that's not true, as in the case of ATP hydrolysis, you need to know why it's not true and the actual concentrations of products and reactants.

Modern biochemistry textbooks have also avoided references to high energy bonds so they tend not to say things like "breaking one phosphodiester bond releases lots of energy." Instead, they concentrate on the "system" that includes all of the reactants and products [Better Biochemistry: The Free Energy of ATP Hydrolysis] [Why Is ATP an Important Energy Currency in Biochemistry?] [The Demise of the Squiggle ].

Here's the problem. Let's say you are an excellent biochemistry teacher and you teach all the right things about metabolism and ATP. Some of what you teach is going to conflict with questions that are on the MCAT because those questions are often based on old fashioned and incorrect biochemistry. What do you do? Are you supposed to teach outmoded concepts so that students can get a good score on the MCAT?

Let's look at three examples from the ATP/ADP website. These are not MCAT questions but the implication is that they could be.

Q: In cellular respiration, which process produces the most ATP?
A: Electron transport chain

Students who learned biochemistry form me (and my textbook) might have trouble answering this question since I don't use the term "respiration." In fact, it is not a prominent descriptive term in most of the modern introductory biochemistry textbooks. (Stryer is an exception.) And even if students understood the question, they might be tempted to answer ATP synthase, if that were one of the choices, since modern biochemistry courses concentrate on teaching that the electron transport chain is responsible for creating a proton gradient but NOT ATP synthesis.

Q: True or false: ATP may be used to regulate certain enzymes.
A: True.

I teach that the answer is mostly false, although there may be some exceptions I don't know about. This is because regulation requires change and the concentration of ATP inside the cell doesn't change very much. If it did, the cell would die. Am I doing my students a disservice by teaching them to think critically?

Q: From one molecule of glucose, how many molecules of ATP will be produced?
A: 32 - 34 molecules of ATP

My textbook says 32 in bacteria and fewer in eukaryotic cells—but not less than 30. The latest versions of Garrett & Grisham and Nelson & Cox (Lehninger) say 30-32. Voet & Voet say 32. Berg & Tomoczko (Stryer) says 30. These answers all refer to ATP equivalents since some of the products are GTP and NADH. The conversion of NADH to ATP depends on the exchange rate but almost all modern textbooks these days use NADH = 2.5 ATP. However, there are still some courses that use the old value (NADH = 3 ATP) and some textbooks from only a few years ago use that value. Their students will be screwed on the MCAT.

The solution to this problem is not to ask such questions on the MCAT but, instead, concentrate on concepts and ideas on order to test for fundamental understanding and not facts. However, even that is going to be a problem since the quality of undergraduate biochemistry courses is quite variable and it's not clear that the correct concepts are always going to be taught.

Fortunately, I don't have to worry about this since I do not intend to alter my textbook to conform to the MCAT. I do not think that biochemistry teachers should be paying any attention to the MCAT in designing their courses1. They should concentrate on teaching biochemistry correctly. The onus is on medical schools to identify students who have a good science education.

1. In discussing this with some colleagues at American colleges, I realized that they are under considerable pressure to offer good pre-med programs. They are charging tuition fees of $20,000 or more and they need to show that their students will get into medical school. That's sad.

[Image Credit: Moran, L.A., Horton, H.R., Scrimgeour, K.G., and Perry, M.D. (2012) Principles of Biochemistry 5th ed., Pearson Education Inc. page 175 [Pearson: Principles of Biochemistry 5/E] © 2012 Pearson Education Inc.]


  1. In theory all of the biochemistry content is also supposed to be from one semester of biochemistry. You can cover all the material expected in one semester but it is superficial and focussed on memorization rather guiding the students to learn concepts and apply previous knowledge to new situations.

    Concept based biochemistry is the way to go. It is far more interesting as well.

    With regards to the amino acids, do you expect students to learn the three letter and one letter abbreviations? I have but make it a small part of the class. The idea being that is part of the language of biochemistry and who wants to be constantly looking them up while reading a paper with 25 mutations. Critical thought and understanding/applying concepts are the major foci of the courses. A biochemistry course should be empowering for students as they apply the physical, inorganic, and organic chemistry they know to understand the structure of biological molecules and how that relates to function.

  2. I remember back in the day in the 2nd year honours biochem class the first words out of the instructor's mouth were, "I know that most of you are pre-med, but I can only give out 25% A's and 75% A's + B's". Like a physician needs to have any clue about how many equivalents of ATP are produced. Just teach to the subject and ignore the MCAT. If students want to well on the MCAT they can take an MCAT prep course, but hijacking the actual discipline to cater to the constituency is a fool's game.