Don’t Run Away.



Steel yourself and look at



You promised!

This better be worth it.

Oh, it totally is. Today, we’re going to talk about biochemical pathways!


Um, because they’re awesome.

We are clearly operating on different definitions of the word ‘awesome’.

Okay, how about because they’re important to understanding medicine?

I’m a writer for a reason. It’s your job to understand medicine.

Point taken. Well, how ’bout this then: How often does someone get poisoned in a fictional story?

I’d say in a good story, every character gets poisoned at least once.

Okay, maybe that’s going overboard a little. But poisons are definitely a useful fictional tool; you see them everywhere from Shakespeare to James Bond.

So poisons are all about biochemistry.

That means I have to give you a framework for thinking about biochemistry before I can even think about talking through one of the most widely-used-for-plot-points categories of illness.

Okay. I’ll try to stay awake.

How magnanimous.

I’m the magnanimous type.

So I see.

Okay, Captain Magnanimous, I want you to picture a marble run.

Dude! You are OBSESSED with marbles!

You said you’d bear with me.

Get to the point, Hoppy.

Well, biochemistry is a lot like a marble run.


Pretend this marble is a molecule of some kind.

We’ll start it out at the top of the marble run. It rolls through a series of maze pieces, like a funnel, or a straight run, or a peg maze. Similarly, the molecule rolls through a series of steps in a biochemical pathway. (The difference between the molecule and the marble is that the molecule gets a structural change with each step.)

By the end of the marble run/biochemical pathway, our marble-molecule might look like this

Or this

Or this.

But regardless, it started out at the top of the marble run, and rolled its way through to the bottom.

So if you put a bunch of marbles through the marble run, you end up with a bunch of marbles at the end. And if you put a bunch of molecules through a biochemical pathway, you end up with a bunch of (altered) molecules at the end.

Biochemistry is totally more complicated than that.

Yeah, it is…but only when you start getting into specifics. I actually just wrote out an explanation of glycolysis and the TCA cycle and the electron transport chain, but it got way too long so I deleted it. Even though it was very marble-y and fun to write.



So here’s the main point. All I wanted to tell you is that even though biochemical pathways look scary and complicated, there are only a few things you really need to know.

1) You start with a molecule.

2) The molecule is transformed in a series of steps, usually designated by an arrangement of arrows, like so:

This says: You start out with a molecule called pyruvate. Pyruvate is converted to a molecule called acetyl CoA. The conversion process also releases a molecule of carbon dioxide, converts a molecule of NAD+ to NADH, and uses a molecule of Coenzyme A.

3) If your eyes are glazing over, this is what you can think about instead:

Here’s a longer pathway:

This says: Pyruvate is converted into acetyl CoA. Acetyl CoA is used to convert oxaloacetate into citrate. Citrate is converted into isocitrate. Isocitrate to alpha-ketogluterate. Et cetera. And around and around. This is called the TCA cycle.

If your brain is trying to implode and suck your eyes into a whirling vortex of madness, here’s what you can think about instead:

Random aside: Here’s a mnemonic to help remember the compounds of the TCA cycle in order: “Our City Is Kept Safe And Sound From Malice.” Isn’t med school fun? For more biochemical mnemonics, you can go here.

4) The transformations designated by the arrows are either spontaneous rearrangements into more thermodynamically happy positions, or are facilitated by helper molecules called “enzymes”.

5) If anything goes wrong in the pathway (ie: if one of the arrows/enzymes doesn’t do its job), the molecules going through the pathway will “back up” behind the problem. It’s like marbles backing up behind a block in the marble run.

6) Some biochemical pathways have split points, like forks in the road. Usually molecules like one path more than the other, and will take that path preferentially. Like if a marble has the choice of shooting down a straight run or taking a turn, it’ll usually shoot down the straight run.

7) If there’s a “backup” in the preferred path, molecules have no problem going down the alternate path. Like if the straight run is blocked by a marble backup, the marbles will instead make the turn and go down the previously less favorable path.


That might be enough for now. Any questions?

Yeah. All those scary complicated biochemistry pathways up there. . . do you know them by heart?

Nope. Not anymore. But I used to, three years ago. First-year Biochemistry class, baby!


I’m actually happy that I did memorize them at one time, to be honest. It was hard to learn the individual pathways, sure. But when you start seeing how everything fits together, you get this overwhelmingly satisfying mental CLICK, and suddenly you’re just blown away by the beauty of the whole thing.

We are clearly operating on different definitions of the word ‘beauty’.

That may be. But just trust me when I say that life is a beautiful, graceful thing. . . right down to the dance of the individual molecules.

Next time, we’ll throw a wrench in the works.

Stay tuned.



Nelson, David L., Cox, Michael M. Lehninger Principles of Biochemistry. 3rd Ed. Worth Publishers, 2000.


Published in: on May 23, 2010 at 12:47 am  Comments (5)  
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5 CommentsLeave a comment

  1. Thanks Dr Grasshopper, I love how you used marbles and marble runs in your explanation – it makes it a lot clearer than it would just using the tables. I also love how you often write dialogue in your explanations, it’s fun – you’re the best kind of geek!

    Also, if I’m right that your “I’ll try to stay awake” was a Princess Bride reference, you rock! Well, you rock either way! ;D

    • Hi, Leah! So glad you’re enjoying yourself! I hope you end up loving this stuff as much as I do!

      And, um….er….ahem…..of COURSE that was an intentional reference! ::cough, cough:: 😀

      Thanks for reading!

  2. Very good info, so add my insight, but I also discuss similar things on my blog.

  3. […] you survived the last biochemistry post! […]

  4. Heheh, I’m in your camp. How incredibly complicated systems work so (apparently) effortlessly IS beautiful! 🙂 🙂 🙂 When I found out about how our genes are constantly turning each other on and off depending on minute environmental changes I almost hyperventilated, so mind blowing awesome!

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