Membranes & Metabolism

Course goals

Upon successful completion of this course, students will be able to: 

Membranes part

1. Name the most important membrane building blocks and describe the molecular organisation and functions of membranes
2. Explain self-assembly and dynamics of (model) membranes based on physico-chemical properties of lipids and proteins
3. Predict how membranes will behave or adapt to specific conditions based on physico-chemical principles
4. Connect lipid biosynthesis and intracellular lipid transport to membrane biogenesis
5. Explain simple techniques used in membrane research
6. Explain how interactions between lipids and membrane proteins can influence the behaviour of these molecules and thereby affect membrane processes
7. Design simple biochemical and biophysical experiments for membrane research
8. Explain why some biochemical or biophysical approaches are suitable for specific research questions and others not
9. Interpret results of biochemical, biophysical and cell biological experiments on membranes and membrane proteins

Metabolism part

10. Describe selected metabolic pathways and their regulation
11. Describe the coordinated regulation of these metabolic pathways
12. Explain metabolic specialisation in liver, muscle and adipocyte tissue
13. Explain catalytic mechanism and allosteric regulation of selected metabolic enzymes
14. Describe oxidative phosphorylation
15. Describe photosynthesis

Content

Content of the course:
Biological membranes consist of complex mixtures of lipids and proteins. The lipids form a permeability barrier and ensure optimal functioning of the embedded proteins. The membrane proteins have special functions such as transport, communication, and energy supply, the latter providing a direct link between membranes and metabolism. This course will introduce you to the versatility of membranes, and to the major metabolic pathways.

The Membranes part of the course starts with the properties of membrane lipids and membrane proteins. You will learn about the physico-chemical properties of various lipids and how they determine the dynamics and organization of biological membranes. Membrane proteins and the functional importance of interactions between membrane lipids and proteins will be discussed. Questions to be addressed include: What makes membrane proteins special? How do you purify membrane proteins and how can you study them? You will get acquainted with biochemical and biophysical techniques, and with the use of self-assembled membrane model systems including proteoliposomes in which membrane proteins are reconstituted. Apart from providing fundamental insights, these systems find applications in medicine-related research, such as drug targeting. The second part of the course switches to membranes and lipids in a cellular context. You will learn about membrane biogenesis, including the biosynthesis and transport of lipids and membrane proteins. Membrane sensors and their role in regulating membrane lipid composition will be introduced.

In the practical you will learn relevant techniques in membrane research, such as making vesicles or nanodiscs, isolating membranes, and analysing lipid composition.

The Metabolism part of the course addresses how (i) cells succeed in the making and breaking of covalent bonds at ambient temperatures using water as solvent and (ii) how they manage to do so at the right moment. In studying metabolism we will be looking at several metabolic pathways, at some of the key enzymes and cofactors involved, at the mechanisms by which the activity of these enzymes is regulated, and at the cellular pathways responsible for ensuring coordinated action of different metabolic pathways within one cell and across different cell types.

A central molecule will be glucose. We’ll study its break-down in the glycolytic pathway, its synthesis in the gluconeogenetic pathway, its storage in the form of glycogen and its conversion to 3-, 4-, 5- 6- and 7-carbon containing carbohydrates in the pentose phosphate pathway. Other pathways that will be addressed are the citric acid cycle; ATP generation by oxidative phosphorylation in mitochondria and by photosynthesis in chloroplasts. 

Relation to other courses:
This course builds on and expands knowledge obtained in the introductory courses in the MBLS foundation in particular Biomolecular Chemistry (MBLS-105; lipids & membranes, glycolysis, the citric acid cycle, oxidative phosphorylation). Students that follow the MBLS themes “Molecules and Cells” and “Molecules and Medicines” are advised to follow this course.

Teaching format (estimation):
Lectures = 20%
Tutorials = 20%
Practical = 10%
Self study = 50%

Grading & Assessment:
In this course, the final grade is determined in the following manner: 

1. Digital exam covering the first part of the course (40%)
2. Digital exam covering the complete course (40%)
3. Practical (20%)

For the average of the two digital exams a 5.5 is the minimal grade to pass
For the practicum a 5.5 is the minimal grade to pass.