Principles of metabolism

This is the home page for the Principles of cellular metabolism PhD course at KI September 2021.

Schedule and location

Detailed schedule for the 2021 course.

The course will run half-time over two weeks. The intention is to have a slower pace so as to give a bit more time to absorb new concepts and also allow time to maintain ongoing experiments, etc during the course. There will be 6 sessions in total (1 introduction).

All seminars this year are at Wiederströmska huset, Tomtebodavägen 18a, Karolinska Campus Solna. See this map.

Course materials

The course is organized around a series of video lectures that highlight important principles and key metabolic pathways. Besides the video lectures, there is required reading. Below, I indicate sections of Stryer’s Biochemistry which is available online, but any major biochemistry textbook (Lehninger / Voet / Devlin) can be used. Details on the enzymatic mechanisms involved can be skipped. Cell Biology by the Numbers by Ron Milo is fantastic for a quantitative understanding of cell biology, and also has some content online.

Material marked further reading is not mandatory, but recommended for those that want to go deeper into specific topics. In the seminars we will also look at some recent examples from the literature.

Lectures

All video lectures are freely accessible on YouTube.

Lecture 1, Introduction. Video PDF

Stryer (6th ed) ch 15.1, 15.2, 15.4 Metabolism: Basic concepts and design or Stryer online sections 14.1 14.3.

Further reading: Almaas et al on the “high flux backbone” of metabolism, another high-level model related to the “bow tie” organization.

Lecture 2, A cell’s material & energy budget. Video PDF

Rolfe & Brown 1997 for an in-depth discussion of energy-producing and consuming processes in cells (very long article, skip the details.) Cell biology by the numbers online sections: cell size, elemental composition and metabolite turnover.

Further reading: Zu & Guppy 2004 on where most ATP comes from — respiration or glycolysis? Hosios et al 2016 describes the quantitative contribution of various nutrients to biomass in cultured cells.

Lecture 3, Oxidation and reduction. Video PDF

Stryer (6th ed) ch 15.3, or Stryer online section 14.2.

Further reading: Hanson 1990 on oxidation numbers.

Lecture 4, Carbohydrates. Video PDF

Stryer (6th ed) ch 16.1–16.3 Glycolysis and gluconeogenesis; ch 20.3–20.4 The pentose phosphate pathway or Stryer online chapters 16.1 16.2 16.3 20.3 20.4

Further reading: Bar-Even 2012 on biochemical constraints that has shaped glycolysis. Westheimer 1987 discusses why evolution chose phosphate groups as energy carriers

Lecture 5, Metabolic Networks and Fluxes. Video PDF

Orth et al 2010 for an introduction to flux balance analysis.

Further reading: Brunk et al 2018 describes the most recent, human metabolic network model. Folger et al 2011 uses flux balance analysis to identify drug targets based on synthetic lethality

Lecture 6, Isotope tracing. Video PDF

Buescher et al, 2015 for an overview of isotope tracing and flux analysis methods.

Further reading: Fan et al 2014 shows an example where isotopic labeling of a product does not imply a net flux.

Lecture 7, The TCA cycle. Video PDF

Stryer (6th ed) Ch 17.1–17.4, The citric acid cycle (skip the glyoxylate cycle) or Stryer online section 17.1 17.2 17.3

Further reading: Owen et al 2002 gives a nice account of anaplerosis and cataplerosis. Hanson 1990 for the redox aspect (the TCA cycle section).

Lecture 8. Cofactors and vitamins. Video PDF

Further reading: Goodman et al 2018 provides an up-to-date account of NAD(P) compartmentalization in the liver

Lecture 9. Energetics and enzyme catalysis. Video PDF

Stryer Ch (6th ed) 8.1–8.4, Enzymes: Basic concepts and kinetics or Stryer online sections 8.1 8.2 8.3 8.4

Further reading: Park et al 2016 combine absolute concentration and isotope tracing data with thermodynamic laws to estimate metabolic fluxes.

Lecture 10. Respiration and oxygen. Video PDF

Stryer (6th ed) Ch 18.2–18.5 Oxidative phosphorylation or Stryer online sections 18.2 18.3 18.4 18.5

Further reading: Sullivan et al 2015 reports an unexpected role for aspartate in hypoxic cells.

Lecture 11. Enzyme classes. Video PDF

Note: in august 2018, the enzyme commission introduced a seventh class (EC 7) for translocases. For now we use the old EC—EC6 system in the seminar, but we will discuss this change.

Lecture 12. Amino acids and nutrient starvation. Video PDF

Stryer (6th ed) Ch 23.3–23.5, Protein turnover and amino acid degradation and Ch 24.1–24.2, The biosynthesis of amino acids or Stryer online section 23.3 23.4 23.5 and 24.1 24.2

Further reading: Wolfson & Sabatini 2017 reviews the sensing mechanisms that help cells respond to amino acid deprivation.

Lecture 13. Measuring metabolism. Video PDF

Liu & Locasale 2017 for a recent overview of metabolomics methods.

Lecture 14. Fatty acids and sterols. Video PDF

Stryer (6th ed) Ch 22.1–22.4 Fatty acid metabolism and Ch 26.1–2 The biosynthesis of membrane lipids and steroids or Stryer online sections 22.1 22.2 22.3 22.4 and 26.1 26.2

Lecture 15. Nucleotides. Video PDF

Stryer (6th ed) Ch 25.1–25.3 Nucleotide biosynthesis or Stryer online sections 25.1 25.2 25.3

Lecture 16. One-carbon units and methylation. Video PDF

Ducker & Rabinowitz 2017 provides an in-depth review of one-carbon metabolism in humans.

Lecture 17. Experimental considerations. Video PDF

Further reading: Cantor et al 2017 describe effects of studying metabolism in a growth medium more similar to human plasma.

Lecture 18. Compartmentalization and Transport. Video PDF

Lecture 19. Genomics. Video PDF

Stryer (6th ed) Ch 27.2 or Stryer online section 30.2