Phospholipids and Glycolipids Self-Assemble to Form a Lipid Bilayer

1. Phospholipids and Glycolipids Self-Assemble to Form a Lipid Bilayer • Driving Forces: • H-bonding • Hydrophobic effect • Electrostatic interactions • Van der Waal’s attractions (close packing)

2. Membrane Fluidity: Temperature, Cholesterol and Fatty-Acid-Composition Regulated How does membrane composition alter with elevated temperature?

3. Significant Lateral Albeit Minimal Transverse Lipid Movement

4. Liposome for Potential Drug Delivery Lipid shape drives overall structure: Wedge micelle bead Cylinder bilayer vesicle

5. Peripheral and Integral Proteins Different membrane orientation (a and e), surface position (f and e) and membrane componentassociation (d and e) What tethers peripheral proteins to the membrane? What secondary structure is common in membrane hydrophobic regions?

6. Hydropathy Plots Identify Potential Trans-Membrane Peptide Regions Hydrophobicity Index: the free energy needed to transfer successive segments of a polypeptide from a non-polar solvent to water Hydropathy Plot

7. Alpha Helices Compose the Integral Protein Bacteriorhodopsin Bacteria light-harvesting protein that generates proton gradient α-Helix most common 2° membrane structure Helical (yellow) and charged (red)residues

8. Bacterial Channel - Porin Beta barrel with a hydrophobic exterior and a hydrophilic core Hydrophobic (yellow) and hydrophobic (white) residues shown

9. Partially-Embedded Prostaglandin Synthase Converts arachi-donicacid (20:4) to prostaglandin H2

10. Aspirin Blocks Prostaglandin Synthase Hydrophobic Channel Prostaglandin stimulates inflammation responses and reduces gastric acid secretion

11. Sodium Gradient Formed via a Na+-K+ATPaseAntiport Pump • P-type ATPases form a phosphorylaspartate and include: • Ca+2ATPases for muscle contraction • Gastric H+-K+ATPases Link http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__how_the_sodium_potassium_pump_works.html

12. Secondary Transport via a Common Sodium Concentration Gradient • Na+-K+ATPaseantiporter gradient drives: • Glucose import via a Na+- glucose symporter • Calcium ion export • via a Na+-Ca+2 • antiporter

13. Digoxin Na+-K+ Pump Inhibition via Dephosphorylation Blocking Digoxin – a cardiotonic steroid medication used for atrial fluttering and heart failure. How can digoxin be chemically described? Digitalis purpurea

14. Motor Protein Actin interacts with the thick filament of myosin causing muscle contraction Thick Filament

15. Myosin Head and Neck Region

16. Myosin-Actin Reaction Cycle

17. Ca+2 Allows for Myosin-Actin Binding Actin How does digoxin affect muscle contraction? Actin

18. Digoxin Na+-K+ Pump Inhibition via Dephosphorylation Blocking Calcium ion export via a Na+-Ca+2antiporter How does digoxin affect Ca+2 abundance? Digitalis purpurea

19. Size Selective Channel Only Allows Potassium Ion Passage • K+ movement: • Down the concentration gradient • From cytosol to cell exterior Cell exterior Cytosol

20. Selectivity Filter Determines the Preference of K+ Over Other Ions Two of four trans-membrane alpha helices shown Dehydrated K+ ions move across the membrane Ionic diameter K+ = 2.66 Å and Na+ = 1.9 Å Why does Na+ not move through this pore?

21. Energetic Basis of Ion Selectivity K+ energy balance: Dehydration versus Carbonyl oxygen resolvation in selectivity-filter lining Does tight K+ binding slow transport across the channel?

22. Electrostatic Repulsion Forces Pushes and Speeds K+ Through Ion Channel • Selectivity filter contains 4 binding sites • Ions move down the concentration gradient

23. Na+ Channel Blocker Specific in blocking Na+ while having no effect on K+ Reversible binding: hydrated Na+ (nsec), tetrodotoxin (0.3 min) Lethal dose in humans: 10 ng Pufferfish: a Japanese delicacy and highly toxic How does this cork-like toxin position itself? Host-toxicity prevention mechanism?

24. Chapter 11 Problems: 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, and 17