Making the Connections: Dissecting Fatty Acid Biosynthesis

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Categories: GSI Online LibraryTeaching Effectiveness Award Essays

by Nicholas Stephanopoulos, Chemistry

Teaching Effectiveness Award Essay, 2008

“Wait, so where are the malonyl CoA subunits again?” the student asked me, peering at the chainlike molecule on the lecture handout with a perplexed look. At the halfway point of Chemistry 135: Chemical Biology, I found myself facing my most challenging office hour yet. Fatty acid biosynthesis, whereby an elaborate enzymatic assembly line strings together precursor molecules called malonyl CoA, had proved a particularly befuddling and frustrating topic for the class. Understanding the molecular acrobatics of the finely tuned protein juggernaut that created these molecules required going beyond memorization and reasoning by analogy, skills that the students had meticulously honed in the past six weeks, to a deeper understanding of the organic chemistry involved.

As a GSI, I fell back on the question that has guided me through countless teaching experiences: when I was trying to learn this topic, what did I wish a GSI had told me to make it truly click in my mind? What allowed me to break past the memorization barrier to deeper understanding was not only seeing many examples of the material (although such exposure is certainly invaluable), but practicing it myself, in different contexts, until I was no longer mechanically applying memorized rules but seeing the underlying science in a way that transformed the awkward and foreign into the familiar and intuitive.

Thus, I took the lecture examples and began showing the students my mental processes. Take the fatty acid molecule and chop it up into two-carbon units, starting at the tail, then draw them out. These two-carbon units, no matter what other atoms are dangling off them, have come from a malonyl CoA precursor. I had the students dissect a molecule (which could range from two to arbitrarily many such units) into chunks of two carbons, and then had them mentally re-stitch together these subunits, one at a time. However, the tricky thing with this biosynthetic pathway lies in the fact that the enzymes involved can, at every step, add or remove molecules from these two-carbon fragments. After adding each unit, I had the students describe what they needed to do to make it “look” like the units in the final molecule. Did they need to remove a hydroxyl? If so, use a dehydrating enzyme, following by a hydrogenating enzyme. By breaking the initially daunting task of deconstructing a behemoth of a molecule into more manageable subunits, and then applying certain rules on those subunits, the students began to not only solve the problem, but develop an intuitive feel for how to approach the process.

I then gave them several new, related molecules to test their understanding. I turned the molecule upside down, added or removed atoms, and changed the order of the enzymes they’d have to use, to force the students to go beyond mere reasoning by analogy. Slowly but surely, I saw the glimmer of understanding in their eyes as they grew increasingly comfortable with the biochemical manipulations and could effortlessly piece together what had formerly been an intimidating molecule. They could even extend their knowledge to related but fundamentally different molecules, like polyketides, employing the same principles in increasingly novel contexts. The experience not only reiterated the value of practice, but showed me that to truly teach someone something I had to remember how I had learned it and convey the critical link that pushed beyond mere regurgitation to true understanding.