This is the home page for the Principles of cellular metabolism PhD course at KI, march 2019.
Schedule and location
The course will run half-time over two weeks, March 11—22. 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 are at Retzius väg 13, Karolinska Campus Solna. See this map.
The course is organized around a series of video lectures that highlight important principles and key metabolic pathways. Besides the video lectures, a biochemistry text book is required reading. Below, I indicate suitable sections of Stryer’s Biochemistry (page number refer to 6th ed), but any major biochemistry textbook (Lehninger / Voet / Devlin) can be used. The further reading material indicated below is not mandatory, but useful to go deeper into specific topics.
In the seminars, we will also discuss recent biomedical research papers and clinical connections.
All video lectures are freely accessible on YouTube.
Lecture 2, A cell’s material & energy budget. Video PDF
Zu & Guppy 2004 on where most ATP comes from — respiration or glycolysis?
Rolfe & Brown 1997 gives an overview of energy-producing and consuming processes in cells.
Cell Biology by the Numbers by Ron Milo is fantastic for a quantitative understanding of cell biology, and also has an online companion site.
Lecture 4, Carbohydrates. Video PDF
Stryer Ch 16, Glycolysis and gluconeogenesis; Ch 20, the pentose phosphate pathway
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
Read Orth et al 2010 for an introduction to flux balance analysis
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
Read Buescher et al, 2015 for an overview of isotope tracing and flux analysis methods
Fan et al 2014 shows an example where isotopic labeling of a product does not imply a net flux
Lecture 8. Cofactors and vitamins. Video PDF
Stryer Ch 15, section on activated carriers & vitamins
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 8, Enzymes: Basic concepts and kinetics
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 Ch 18, Oxidative phosphorylation. pp. 501 – 503, 506 – 522, 527 – 532.
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 Ch 23, Protein turnover and amino acid degradation, pp. 656 – 663, 666 – 672; C 24, The biosynthesis of amino acids. pp. 683 – 693, 700 – 705.
Wolfson & Sabatini 2017 reviews the sensing mechanisms that help cells respond to amino acid deprivation.
Databases and websites
The eQuilibrator tool for Gibb’s energy calculations
PubChem for exact masses of compounds
Problem collections for seminars
Problem collections are being updated, and will be handed out at each seminar. I will post each collection here after the seminar.
Flux balance analysis lab excel file