Wednesday, 6 June 2018

SF Metabolism

The structure of Metabolism (Biochemistry II) wasn't quite as clear as that of Cell Structure & Function (Biochemistry I) but it was basically broken up into 4 parts. It also wasn't taught as a flipped classroom and had less CA (30% CA rather than 35%), but still more than most Bio modules (25%). 

It ended up being possibly my favourite module, although that was much more to do with my Schols study and study from the textbook than with the lectures, for a couple of reasons:

  • the lectures were very difficult and went very fast - I remember being completely overwhelmed by Lipids because he went so fast, so that's when I went to the library and took out Lehninger's Biochemistry which was awesome because it started from basics and took me all the way through to an advanced level. I then just continued studying from Lehninger for Schols and I think that really helped me get it -- so maybe it was good that those Lipids lectures were so unapproachable at first!
  • the book had more context and interesting tidbits/additional information about the topic which made it extra interesting to study
In general the major feature of this course is that I didn't learn it from the lectures, so I was actually looking at some lectures the night before the exam like 'huh, didn't know they covered that' [but thankfully I'd already covered almost all of it except fat mobilisation for Schols, and I covered fat mobilisation the night before which was lucky because it then came up]. I did really love the subject though, especially regulation of metabolism -- just one example is the reciprocal regulation of fatty acid synthesis and breakdown via beta-oxidation to make sure they don't go on at the same time which would just waste energy, and one method of doing this is that malonyl-CoA, the precursor for FA synthesis, inhibits carnitine acetyltransferase 1, which is needed to transport long-chain fatty acids into the mitochondria for oxidation.

I also liked learning about hormones controlling regulation of loads of different targets simultaneously, and of hormones like insulin and glucagon opposing each other both directly and indirectly. 

It makes me a bit sad that I'm going to gradually forget what I learned from this module and already have forgotten a bunch compared to what I knew for Schols, but I guess that's how it is and I still have my folder bursting with notes to look back on.

We had a tutorial each week run by 3rd years who'd done well in the course last year. They were useful, and I think the most useful thing was when one of the tutors told us that metabolism is all about paths leading to acetyl-CoA and feeding into the TCA cycle, because that really helped to make sense of Metabolism as a highly integrated process rather than a list of separate pathways. I'd probably now say it's more about gathering electron carriers so they can lead into oxidative phosphorylation, but it was a really helpful way to think about the products of glycolysis and fatty acid oxidation.

Another sort-of profound realisation was that it doesn't really end anywhere. I think the whole time I was implicitly expecting metabolism to culminate in something but eventually I realised that it just works to work; you stay alive to stay alive longer (and reproduce but that's not directly related). Oxidative phosphorylation is probably the closest thing to a culmination, but even that just produces ATP which is then used to fuel all the other processes needed for all the metabolic reactions (and a few building processes too probably like building structural proteins) that then lead back to .... oxidative phosphorylation. It sustains itself just because. Life replicates itself just because it can.

Part 1: Carbohydrate Metabolism

  • Glycolysis & its regulation
  • Gluconeogenesis & its regulation
  • TCA Cycle & Pentose Phosphate Pathway (did not know ths was taught in this section at all because, as above, I did it all from a textbook which luckily closely matched what we needed to know, probably because this was a course on the really major biochemical pathways)
  • Glycogenolysis & glycogen synthesis
Part 2: Lipid Metabolism
  • Properties of lipids (structure, function, diversity)
  • Mobilisation of lipids, the carnitine transporter and oxidation of fats
  • fatty acid synthesis
  • cholesterol biosynthesis
Part 3: Bioenergetics (taught by the sweetheart Derek Nolan who was great because he so clearly loves oxphos)

  • bioenergetics - displacement from equilibrium, redox potential, electrochemical gradients - found loads of fascinating stuff about this in Lehninger and oh boy am getting worried I didn't get this topic down right in the exam
  • the electron transport chain
  • two lectures on oxidative phosphorylation i.e. Peter Mitchell's chemiosmotic hypothesis for how ATP is made from ADP via coupling to the electron transport chain + experimental evidence
  • light reactions of photosynthesis
Part 4: Amino Acid Metabolism

  • nitrogen fixation and assimilation
  • functional groups and aminotransferases e.g. glutamate --> a-ketoglutarate is a path into the TCA cycle
  • urea cycle
  • pathologies associated with amino acid metabolism e.g. phenylketonuria, Hartnup disease
I didn't really study amino acids much at all and I don't think many people did. I did a bit on it for schols but definitely not in the depth I did other things.

Part ?: Miscellaneous we had some scattered additional lectures on lipids: lipidemias and lipoprotein metabolism, and we were supposed to have one on bile salts as well but thankfully that got cancelled. 


We had three labs: 

  • subcellular fractionation - we were assigned to either citrate synthase (a mitochondrial enzyme used in the TCA cycle) or lactate dehydrogenase (a cytosolic enzyme) and had to I think figure out which one we had or what part of the cell we were working with by measuring the activity of the enzyme, since they'd be higher in different parts of the cell.
  • Lipids - this was actually more of a lecture, it just happened to take place in a lab. We were taught about lipids and shown some paper chromatography data from lipid experiments that we then had to work with in an assignment
  • Oxidative Phosphorylation -- this one was very cool; we investigated oxidative phosphorylation by hooking a bunch of respiring mitochondria in a tank to a chart recorder and doing different things to them to see how that changed the amount of oxygen consumed, so for example adding ADP dramatically increased oxygen consumption (because oxphos is obligately coupled to oxygen consumption via the respiratory chain) and adding inhibitors to stop ATP synthesis or block specific complexes in the electron transport chain, showing the order of the complex - so you can recover from a rotenone (complex I) block by adding succinate, but not from antimycin A which inhibits Complex III which is past succinate dehydrogenase. It was very intense, since the inhibitors actually do inhibit respiration, and the manual said something like 'Be very careful as all of these inhibitors are poisonous and there are no specific antidotes'. Just like, so poisonous since they specifically block breathing. Luckily we didn't have cyanide, which blocks the very last complex and thus can't be recovered from with a different fuel. 

My favourite parts were Bioenergetics (easily) and then Lipids, and those were the essays I did in the exam. I really hope I did well in them; unfortunately I'd forgotten a ton since I did the bulk of my study back in November and the exam was in May. Especially with the oxphos essay I did for Schols - I smashed it for Schols, but then did the same one (presumably marked by same lecturer) for the summer exam, just worse because I'd forgotten details, so they're just gonna be seeing a worse version of an essay they've read before (in fairness I had 10 modules to study for in between). Scary! 

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