Hello Again, Metabolism!

by Amy Cheng Vollmer

Source.

Years ago, pathways of intermediary metabolism made up a significant portion of biochemistry and microbiology courses. Therein, students learned about interconversions and connections between pathways, and they could follow the carbons as they moved from acetate into the cholesterol molecule and many others. But the advent of exciting new methodologies—structural biology, recombinant DNA, molecular genetics, immunochemistry, probes, blots, microarrays, metagenomics, and more—crowded much of metabolism right off the syllabus. Given that teaching pathways could be dry and boring, faculty often elected to substitute more trendy and exciting topics instead. To be sure, they thought metabolism was important, but assumed ‘someone else must be teaching it.’

The result is a generation of well-trained scientists who can clone or crystallize just about anything and can harvest bushels of data from vast microarrays. But once those gene names are converted into enzymes, they are not so adept at mapping their enzymatic steps into a coherent and integrated system of pathways. In fact, a survey I instigated at an IMAGE (Integrating Metabolism and Genomics) meeting in 2004 showed that the vast majority of individuals trained after the 1970s knew little about the pathways of photosynthesis or of amino acid, purine, and pyrimidine biosynthesis, nor did they think that needed to be taught at the undergraduate level.

So we now have faculty (in the assistant and associate ranks) who admit to me that they would have a tough time teaching pathways effectively because they don’t know much beyond glycolysis and the Krebs cycle. Yet, in the past 5 years, I have found time and again that some of the most revealing presentations at the ASM meetings (and others) have shown that important signals in microbial processes are, in fact, small metabolites, and that the key enzymes are not specific to pathogenesis, development (e.g., sporulation) or differentiation (morphotypes), but rather they are the enzymes of the Krebs cycle or for key steps in nitrogen or phosphate metabolism. Imagine that!

In this era of metagenomics, metabolism has resurfaced dressed fashionably as metabolomics: the study of the universe of small molecule metabolites that characterize a biological sample, usually one containing many different species, e.g., the metabolome of the human gut or the cow’s rumen. Somehow the profiles of small molecules reveal important aspects of the health of such ecosystems. So now we find faculty and students scrambling to teach and learn about primary and secondary metabolic pathways so that they can find their way through the vast databases that are being assembled from structures, pathways, regulatory networks, etc.

Metabolism is enjoying a renaissance in our curricula and it is about time! There are vast secrets about biology to be revealed by the small molecules. Understanding how their levels rise and fall will take a careful study of the enzymatic pathways leading to and from them. So hello again, Metabolism! It’s so nice to have you back where you belong.

Amy is Professor of Biology, Swarthmore College, and President of the Waksman Foundation for Microbiology.

Comments

[John Ireland]

I teach at the community college level and our microbiology class is overwhelming populated by pre-nursing students who have not been required to take a chemistry or biology class before micro. In this environment I knew it made little sense to shove pathways into them, as they would simply and painfully leak back out. Rather, I take a more evolutionary approach to the idea, trying to get them to understand the big picture of the interconnectedness of the pathways and the reasons why they make sense as a whole. Sprinkle a few pointed, specific examples in the mix (typically involving a picturesque pathogen) and leave some "black boxes" along the way that they can fill in later.

[Stanley Maloy]

It isn't simply evolution ... Metabolism underpins everything cells do, from acquiring energy through regulation through determining fitness in a particular environment. I think the problem is that so many biochemistry teachers focus on memorization (a "killer"for budding laboratory scientists) rather than the big picture. When I took biochemistry we were expected to memorize a bunch of pathways but never learned about interconnections between them or why it mattered to the cell. It was only when I took finally microbiology that it all made sense.

[Psi Wavefunction]

I'd love to learn about metabolism, if it were taught with a pinch of evolutionary perspective, and phylogenetically-informed. In my experience, it sure as hell was neither - in a general biochem course, we were forced to cram pathways and enzyme names specific to humans. Now, that's great for the premeds, but utterly useless to someone interested in general biology.

But it doesn't even need to be so. One night, frustrated at having to memorise the urea cycle when I figured my organisms don't even have a urinary system, I decided to look up whether that cycle had anything to do outside metazoa. Turns out, it does. In fact, it has some quirky involvement in plants (apparently, part of the cycle happens in roots and the other part in the mycorrhizal symbiont); exists in a wide variety of various protists as well - for some odd reason, diatoms have the complete thing, despite not needing a specialised system for secreting nitrogenous wastes as they can simply exocytose them. The urea cycle is NOT 'for' nitrogenous waste removal, and has been exapted for many other purposes, depending on which components were in excess and demand. It even exists in bacteria, and may perhaps be quite fundamental to life.

I still failed that portion of the midterm, as through all my wanderings in the literature I managed to not retain any of the complicated enzyme names, but realised that there ARE better ways of teaching it. I think a more general approach is essential, as enzyme names themselves don't matter -- what's important is how this cycle got there, and how it became utilised in various circumstances.

Too bad there seems to be a law against biochemists actually understanding evolution (I know I'm overgeneralising, but...don't get me started on my biochem TA. ARGH.) or any non-Tree-of-Life person having the slightest clue about how the modern phylogeny really looks. I think they are wrongly ignoring some potentially very useful tools for teaching as well as their own research.

[Mark O. Martin]

This takes us back to Julian Davies' idea about the "parvome"---universe of small mw molecules secreted (and within) each organism. It's all information!

Amy is right that many students (and professors) don't like learning or teaching pathways. But they remain fascinating and useful.

It's all context, and it is all interrelated.

Great post, from an inimitable author.