Course: Principles of Biochemistry
Length: 15 weeks, 4-6 hrs/wk
Instructor: Alain Viel, Rachelle Gaudet
Principles of Biochemistry integrates an introduction to the structure of macromolecules and a biochemical approach to cellular function. Topics addressing protein function will include enzyme kinetics, the characterization of major metabolic pathways and their interconnection into tightly regulated networks, and the manipulation of enzymes and pathways with mutations or drugs. An exploration of simple cells (red blood cells) to more complex tissues (muscle and liver) will be used as a framework to discuss the progression in metabolic complexity. Learners will also develop problem solving and analytical skills that are more generally applicable to the life sciences.
If I seem to have been quiet lately, it’s partly because I’ve been taking this course. It’s massive. Not just the amount of content, but the detail involved. While it wasn’t particularly creative or engaging (with a couple of notable exceptions), it was exactly the material I wanted (and needed) to cover, so I’m delighted I enrolled.
It’s listed as an intermediate course, and recommends college-level biology and chemistry, including organic chemistry. So here I go setting the record for courses taken requiring orgo without ever having taken it other than what’s on YouTube (and let me say again, Leah4Sci and The Organic Chemistry Tutor have some great vids that have been very helpful in filling in some gaps; but would someone please do a full-on OC mooc?). But while there wasn’t anything I’d never heard of before, I suspect someone with a stronger chemistry background might have an easier time of it. After all, I still have to stop and think every time someone says “carboxyl group.” And don’t even talk to me about nitrogen.
Much of the content is in the form of metabolic pathways: glycolysis, for example, or the synthesis of fatty acid chains, along with regulatory mechanism and interrelations. It’s like one giant Butterfly Effect: one thing gets a little out of whack, and all kinds of things happen as the body tries to maintain homeostasis. Molecular energetics, protein structure, enzymatic mechanisms, it’s a broad spectrum of topics alongside the metabolic pathways. Clinical applications look at diabetes, gout, and a few other metabolic diseases, as well as a unit on the use of PET scans in tracking in vivo pathways.
It was a pretty grueling course, partly because so much of it went like this:
One of the subunit of the activated small G protein will in turn activate a membrane-bound enzyme called an adenylyl cyclase, which catalyzes the conversion of ATP into cyclic AMP. The concentration of cyclic AMP rises and cyclic AMP interact with the protein Kinase called protein Kinase-A, or PKA. This Kinase will become activated and then will phosphorylate PFK-2 on the Kinase domain.
The phosphorylation of PFK-2 will result in the inhibition of the Kinase domain and the activation of the Phosphatase domain. Therefore, PFK-2 will catalyze the conversion of Fructose 2,6-bisphosphate back into Fructose-6-phosphate. The concentration of Fructose 2,6-bisphosphate in the cell decreases, and PFK-1 activity will decrease as well.
While all that actually makes sense when you break it down (if you can remember what PFK and AMP are, since you’ve encountered a dozen new enzymes in two days), it’s kind of insane on the first six or twelve takes.
The lectures tend to have a question-and-answer structure, although the answers are so extensive, it’s often hard to remember there was a question, let alone what it was. “Why does HSP70 production increase with heat stress?” “How does the potential cell membrane bend to form a sphere?” Sometimes these questions are asked by the lecturer, sometimes by an off-camera TA. One of those TAs did a very kinetic presentation on glycolysis, sliding bits of paper around to describe the various steps. A couple of brief video clips from other providers added to the presentation on diabetes. And the PET scan section was presented by a different professor entirely. So there was some variety in the presentation.
The course wasn’t all multisyllabic strings of chemicals. For instance, fun fact: in the 40s when biochemists were first trying to figure out protein folding, one of the proteins they used was RNAse A, also known as bovine pancreatic ribonuclease. The Armour meat packing company – maker of Hot Dogs, Armour Hot Dogs, What Kind of Kids Love Armour Hot Dogs – just happened to have purified a kilogram of this stuff, so gave it out to scientists to study, which helped a great deal. Don’t think to hard about why a hot dog company was purifying bovine enzymes in the 40s. You don’t want to go there.
Graded material included a few questions after each video, plus a unit quiz at the end of one to three sections. Most of the questions were information-retrieval multiple choice, with two or three chances at each, meaning my grade far exceeds my grasp. But that’s ok, I’m not relying on this as a true measure of understanding. That’s why I’m going through it all again, just to get it to sink in a little better.
One of the great ancillary benefits that had nothing to do with the course itself was my dive into Cerego. I’ve been a fan of the spaced-repetition flashcard site (for lack of a better term) for a while now, finding all kinds of interesting things in their Public Library, both pertaining to moocs I’m taking, and just other stuff like countries and capitals and brain anatomy. But they suddenly discontinued access to the Public Library; if I wanted to use a memory set for glycolysis, was going to have to make one myself. I’ve tried to do this before, but was never happy with the results and was fine with what someone else had to say about chemical groups or DNA replication. But now I have my own set for biochemistry! I’m like a kindergartener who just brought home her first finger painting.
Optional ungraded assignments using PyMol were also included. Because this required downloading software, and I’d just replaced my old computer (it kept threatening to set itself on fire), I didn’t want to fool around with extra stuff. The assignments look interesting; now that I feel more relaxed about both my computer, and my time, I think I’ll take a crack at it as I go through the material again (adding more Cerego modules every day…).
I was very pleased with this course. I suspect its value depends on the background and motivations of the student: it might not be the best place to start for someone with only mild curiosity about biochemistry and metabolism (another Harvard mooc, “Cell Biology: Mitochondria” is a lot gentler, and far more visually appealing), but even those with a weaker background, like me, can find this beneficial if enough effort and outside remedial work is mixed in.