NOTE: This document has it’s origins in Lecture 3, but ends up being applicable to Lectures 4 and 5 too.

I got though lecture 3 a little faster than last year.

I think this was largely due to the lovely drawing that summarized the fatty acid and glucose oxidation pathways

From there it was easy to show the fate of the NADH/FADH2

The concepts above are mainly covered in Chapter 17… although at this stage I’ve really given a different emphasis from the ‘molecular mechanisms’ approach in Voet & Voet. Instead, I concentrated on the CONTROL of the machinery above.

However, lets go through the pages…

p546 starts with a nice summary of the overall process (fuel plus oxygen gives carbon dioxide and water) but makes the point that the CO2 production and the oxygen consumption parts are kept separate…. It also confirms that the general strategy is to react hydrogens with oxygen in a controlled, step-wise manner and that the energy liberated is captured in a proton gradient.

We didn’t really cover the material in Section 1 on the mitochondria – partly because I assume that you already know about mitochondria but also because the information is more detailed than we really need to know. However, Figure 17-2 is essential and you should be familiar with the text on p547. Note the paragraph at the top of p548 which makes the point that the foldings of the inner-mitochondrial membrane make it easier to make a ‘local’ proton gradient (ie, to stop the protons from diffusing too far away!).

The first paragraph of Section 1.B talks about the fact that the inner mito membrane is very impermeable (especially to protons) BUT that it lets the gases oxygen and carbon dioxide in and out. We’ll talk about the bit on the transport of ‘cytosolic reducing equivalents’ in Lecture 4… but clearly you might have spotted that the Hs generated during glycolysis need to come into the mitochondria – both to generate ATP but, more importantly, to keep up a supply of NAD for glycolysis to continue.

The bit about the transport of ATP/ADP is also something we’ll mention in Lecture 4…. As is the transport of phosphate.

Section 2 on Electron Transport is WAY too detailed for what we need to know…. But we will cover some of the mechanistic/structural stuff in Lecture 4/5.

Section 3 on oxidative phosphorylation (this is the posh word for the synthesis of ATP at the F0F1ATPase). I *do* wish for ht eday when people wouldn’t talk about the “Chemiosmotic Theory”… it’s FACT. But, even though it has been well established for decades, and even though we can actually SEE the machinery of the F0F1ATPase, textbooks still sneer by calling it a ‘theory’… very strange. Still, the stuff on p568 is excellent.

What’s both beautiful and confusing, though, is Figure 17-20. On the one hand, it seems to imply that the inter-membrane space is desperately important in holding the proton gradint, but then it points out that the ‘intermembrane space is equivalent to the cytoplasm because the outer membrane is permeable to protons”.

ReadingBox 17-2 is quite inspirational… Peter Mitchell is a hero of mine – a good example of someone who wasn’t intimidated by the pompous establishment… and a fine example of what you can do in your own garage!

Don’t bother with Box 17-3, but the stuff at the bottom of p570 is helpful in emphasizing that the proton gradient is a lovely store of potential energy because of the pH difference AND the ionic difference (ie, +ve charges more on the outside). The equation and stuff about free energy aren’t necessary, though.

Section 3-B on the ATP Synthase is pretty essential – but will be covered more in Lectures 4 and 5. Although “all you’ll need to know for the exam” (don’t we academics love it when that’s the only question we get asked ) is Figure 17-25 and Figure 17-26, the details in the text surely help in interpreting those figures. So you won’t be TESTED on the details of the structures given on p572 or p573, but appreciating IN GENERAL TERMS what each of the subunits DO and how the machine functions to convert a proton movement into ATP is essential – and thinking about the stuructures must help you in this regard. Understading the binding change model (p575) is important.

The beautiful experiments shown on p576 that show the ‘rotary engine’ characteristics of the F1ATPase are also important in helping you understand how the machine works…. But you won’t be tested on this fine detail.

Section 3-C on the P/O ratio is something we’ll sort of cover in Lectures 4/5… it really just means the stoichiometry of the whole process (ie, how many ATPs do you get from each H that goes down the chain). The important thing to realize here is that there’s still some debate on the ratio… so all those texts (and, dare I say, exam questions) that talk about a certain yield of ATP for a glucose molecule are silly.

Section 3-D is something we cover in Lecture 4 – but is essential. TOTALLY!!!

Section 4 is great for the first paragraph, but, in part A, completely misses the point. Instead of doing what we did (ie, talk about back pressure regulating the pumps, and the importance of having cofactors like NAD and ADP available) it tries to adopt a confusing thermodynamic approach!

The only good thing about this section is on p582 where the newly discovered IF1 protein (that stops the machine operating in reverse!) is mentioned.

Section 4-B talks about the grander contol of the pathways that supply the NADH and clearly we’ll do that in much more detail when we cover those pathways… but Figure 17-29 is a good ‘taster’ for how one pathway can affect another.

Section 4-C is really germane to your Radioactivity practical because it talks about how yeast cells can switch from aerobic to anaerobic metabolism (or vice versa) as dictated by prevailing oxygen levels.

Box 17-5 is great for emphasizing the importance of matching the rate of ATP generation to the rate of ATP usage… and the dire consequences when this becomes impossible.

Don’t worry about the stuff on p585 on reactive oxygen species (although this *is* really interesting, it’s not part of the course).

Textbook Website Bonuses

I don’t really think much of the animated figures (17-8, 17-20, 17-26 and 17-29) – the animations don’t really seem to help understanding… but perhaps you think differently. Each of the animations does, at least, test something that you need to know (ultimately!).

The guided exploration that accompanies Section 2-B (ie, the one on oxidative phosphorylation and electron transport) is SUPERB. It is a lot more detailed than the coverage I’ll give (or expect), but it is SO WELL EXPLAINED and animated that it really should not phase anyone. Particularly useful is the narrators ‘script’ that you could print out.

Don’t worry about the Q-cycle guided exercise, but the ATPase one is worth playing with. You can really get a feel for the shape of the alpha- and beta-subunits and the way the gamma-subunit fits in (and how it is asymmetric).

The interactive exercises are largely pointless… The ferredoxin one is fun to rotate around but doesn’t really teach us anything special. Similarly arcane are the Complex III pictures, and the cytochorome c graphics. These interactive depicitons are BEAUTIFUL and inspiring but I don’t think that we could really TEST any of this information!! The ATPase picture is fantastic (I LOVE this enzyme) but doesn’t really do any more than the guided exploration.

The self-test is a bit fussy. I only got 73% (but that includes the answers where I said “stupid question, picky answer… I don’t care”)… still worth doing though.