Principles of metabolism

This is the home page for the Principles of cellular metabolism PhD course at KI, march 2019.

Schedule and location

Detailed schedule for the 2019 course.

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.

Course materials

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.

Lectures

All video lectures are freely accessible on YouTube.

Lecture 1, Introduction.  Video  PDF
Stryer Ch 15, Metabolism: Basic concepts and design

Lecture 2, A cell’s material & energy budget.  Video  PDF
Further reading:
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 3, Oxidation and reduction.  Video  PDF
Stryer Ch 5 on oxidation-reduction reactions.
Further reading:
Hanson 1990 for more on oxidation numbers.

Lecture 4, Carbohydrates.  Video  PDF
Stryer Ch 16, Glycolysis and gluconeogenesis; Ch 20, the pentose phosphate pathway
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
Read 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
Read 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 Ch 17, The citric acid cycle. (skip the glyoxylate cycle)
Further reading
Owen et al 2002 gives a nice account of anaplerosis and cataplerosis

Lecture 8. Cofactors and vitamins.  Video  PDF
Stryer Ch 15, section on activated carriers & vitamins
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 8, Enzymes: Basic concepts and kinetics
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 Ch 18, Oxidative phosphorylation. pp. 501 – 503, 506 – 522, 527 – 532.
Further reading:
Sullivan et al 2015 reports an unexpected role for aspartate in hypoxic cells.

Lecture 11. Enzyme classesVideo  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.
Further reading:
Wolfson & Sabatini 2017 reviews the sensing mechanisms that help cells respond to amino acid deprivation.

Lecture 13. Measuring metabolism.  Video  PDF
Read Liu & Locasale 2017 for a recent overview of metabolomics methods.

Lecture 14. Fatty acids and sterols.  Video  PDF
Stryer C 22, Fatty acid metabolism. pp. 617 – 626, 631 – 641; Ch 26. The biosynthesis of membrane lipids and steroids. pp. 732 – 742.

Lecture 15. Nucleotides.  Video  PDF
Stryer C 25. Nucleotide biosynthesis. pp. 709 – 723.

Lecture 16. One-carbon units and methylation.  Video  PDF
Further reading:
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
Chapter 27. The integration of metabolism. pp. 760 – 770.  This contains some discussion of the role of various tissues.

Databases and websites

HumanCyc database

Kyoto Encyclopedia of Genes and Genomes (KEGG)

BiGG model repository @ UCSD

Human Metabolome Database (HMDB)

BRENDA, the comprehensive enzyme information system

BioGPS gene expression portal

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.

Problem collections: seminar 1, seminar 2, seminar 3, seminar 4, seminar 5

Flux balance analysis lab excel file

T cell gene expression data:  excel file  KEGG gene list
The KEGG pathway map tool