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Teaching the design principles of metabolism

Nature Chemical Biology volume 8, pages 497–501 (2012)Cite this article

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Learning metabolism inevitably involves memorizing pathways. The teacher's challenge is to motivate memorization and to help students progress beyond it. To this end, students should be taught a few fundamental chemical reaction mechanisms and how these are repeatedly used to achieve pathway goals. Pathway knowledge should then be reinforced through quantitative problems that emphasize the relevance of metabolism to bioengineering and medicine.

The importance of metabolism is beyond dispute. Metabolic enzymes constitute up to 25% of genes in microbes and 10% of those in humans1,2. Collectively, these enzymes perform the remarkable feat of converting unreliable supplies of incoming nutrients into balanced amounts of energy and biomass precursors. In microbes, the activities of these enzymes can be intentionally rewired to produce high-value products, including biofuels3,4. In humans, undesired metabolic imbalances can lead to obesity, diabetes and cancer, and drugs that attempt to restore normal metabolite concentrations are among the most prescribed pharmaceuticals.

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Figure 1: Reactivity of bonds β to carbonyl.
Figure 2: Example networks for teaching flux balance analysis.
Figure 3: The cancer-associated pyruvate kinase isozyme (PKM2) offers a modern case study for teaching metabolic regulation by isozyme switching, allostery and covalent modification.

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Acknowledgements

We thank Shawn Campagna for help in designing this curriculum, David Botstein for his tireless support of innovative teaching, Bernhard Palsson for guidance teaching flux balance analysis, and NSF CAREER Award MCB-0643859 to J.D.R. for supporting the curriculum development.

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Authors and Affiliations

  1. Joshua D. Rabinowitz is in the Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.,

    Joshua D Rabinowitz

  2. Livia Vastag is in the Department of Chemistry, Castleton College, Castleton, Vermont, USA.,

    Livia Vastag

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  1. Joshua D Rabinowitz
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  2. Livia Vastag
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Correspondence to Joshua D Rabinowitz.

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Rabinowitz, J., Vastag, L. Teaching the design principles of metabolism. Nat Chem Biol 8, 497–501 (2012). https://doi.org/10.1038/nchembio.969

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