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1. When viewed by electron microscopy, the lipid bilayer is often described as looking like a railroad track. Explain how the structure of the bilayer creates this image.

2. Explain the following statement: The structure of all biomembranes depends on the chemical properties of phospholipids, whereas the function of each specific biomembrane depends on the specific proteins associated with that membrane.

3. Biomembranes contain many different types of lipid molecules. What are the three main types of lipid molecules found in biomembranes? How are the three types similar, and how are they different?

4. Lipid bilayers are said to behave like two-dimensional fluids. What does this mean? What drives the movement of lipid molecules and proteins within the bilayer? How can such movement be measured? What factors affect the degree of membrane fluidity?

5. Why are water-soluble substances unable to freely cross the lipid bilayer of the plasma membrane? How does the cell overcome this permeability barrier?

6. Name the three groups into which membrane-associated proteins may be classified. Explain the mechanism by which each group associates with a biomembrane.

7. Identify the following membrane-associated proteins based on their structure: (a) tetramers of identical subunits, each with six membrane-spanning α helices; (b) trimers of identical subunits, each with 16 β sheets forming a barrel-like structure.

8. Proteins may be bound to the exoplasmic or cytosolic face of the plasma membrane by way of covalently attached lipids. What are the three types of lipid anchors responsible for tethering proteins to the plasma-membrane bilayer? Which type is used by cell-surface proteins that face the external medium? By glycosylated proteoglycans?

9. Although both faces of a biomembrane are composed of the same general types of macromolecules, principally lipids and proteins, the two faces of the bilayer are not identical. What accounts for the asymmetry between the two faces?

10. What are detergents? How do ionic and non-ionic detergents differ in their ability to disrupt biomembrane structure?

11. What is the likely identity of these membrane-associated proteins: (a) a protein that is released from a membrane treated with a high-salt solution, which causes disruption of ionic linkages; (b) a protein that is not released from the membrane upon its exposure to a high-salt solution alone, but is released when the membrane is incubated with an enzyme that cleaves phosphate-glycerol bonds and covalent linkages are disrupted; (c) a protein that is not released from the membrane upon exposure to a high-salt solution, but is released after the addition of the detergent sodium dodecylsulfate (SDS). Will the activity of the protein released in part (c) be preserved following its release?

12. Following the production of membrane extracts using the non-ionic detergent Triton X-100, you analyze the membrane lysates via mass spectrometry and note a high content of cholesterol and sphingolipids. Furthermore, biochemical analysis of the lysates reveals potential kinase activity. What have you probably isolated?

13. Phospholipid biosynthesis at the interface between the endoplasmic reticulum (ER) and the cytosol presents a number of challenges that must be solved by the cell. Explain how each of the following is handled.

14. What are the common fatty acid chains in phosphoglycerides, and why do these fatty acid chains differ in their number of carbon atoms by multiples of 2?

15. Fatty acids must associate with lipid chaperones in order to move within the cell. Why are these chaperones needed, and what is the name given to a group of proteins that are responsible for this intracellular trafficking of fatty acids? What is the key distinguishing feature of these proteins that allows fatty acids to move within the cell?

16. The biosynthesis of cholesterol is a highly regulated process. What is the key regulated enzyme in cholesterol biosynthesis? This enzyme is subject to feedback inhibition. What is feedback inhibition? How does this enzyme sense cholesterol levels in a cell?

17. Phospholipids and cholesterol must be transported from their site of synthesis to various membrane systems within cells. One way of doing this is through vesicular transport, as is the case for many proteins in the classic secretory pathway (see Chapter 14). However, phospholipid and cholesterol membrane-to-membrane transport in cells does not occur solely by vesicular transport. What is the evidence for this statement? What appear to be the major mechanisms for phospholipid and cholesterol transport?

18. Explain the mechanism by which statins lower “bad” cholesterol.