Membranes and Transport

1. Membranes and Transport (Keeping the in in and the out out)

2. Lipid Aggregation • Like dissolves like • Polar part interacts with water • Head groups • Cholines, phosphates, serines etc • Nonpolar parts stay away from water • Fatty acid tails • Form micelles or bilayers

3. Lipid Structures In water

4. Fluid Mosaic Model of Cell Membranes

5. Fluid Mosaic Model of Cell Membranes • Membrane mostly lipid • PC, PS, PE etc • Also glycolipids • Cerebrosides and gangliosides • Protein scattered throughout • Integral • Peripheral • Specifics depend on membrane • Proteins in a lipid ocean • 2D diffusion

6. Membranes Assymetrical • Lipids • Inner v outer leaf • Large barrier to transfer between leaves • In general smaller on inner leaf • Inner leaf less roomy • Gangliosides on outer • Proteins • Different in different leaves • Different roles

7. Transport across the membrane • Moving particles • Diffusion • Simple • Facilitated • Active Transport • Endocytosis • Receptor mediated endocytosis • Moving information • Signal transduction

8. Diffusion • With concentration gradient • Swimming downstream • Simple • Molecules moving with gradient • Osmosis • Uniport • Symport • antiport • Facilitated • Uses carrier • Carnitine example

9. Active Transport • Requires Energy in the form of ATP • Against concentration gradient • Example: Na+/K+pump • Enzyme is Na+-K+-ATPase • 3 Na+ ions move in 2 K+ ions move out

10. Active Transport

11. Sodium Potassium Pump • Maintains an electrical gradient that is the basis for excitability in nerve and muscle cells. Where is the cell more negative? Inside or out? Inside! This is important for propogation of signals in neurons • Export of sodium from the cell provides the driving force for several facilitated transporters, which import glucose, amino acids and other nutrients into the cell. • Creates an osmostic gradient that drives absorption of water. Examples are found in small intestine and in the kidney.

12. Voltage Gated Channels some electrical event triggers the voltage-gated channels to open • Changes in cell voltages such as a signal moving down a neuron • the Na+ V-gated channel opens immediately • Na+ ions flood into the cell (along their concentration gradient) • the K+channel opens AND the Na+ V-gated channel inactivates • K+ ions flood out of the cell (along their concentration gradient) • the Na+/K+ pump uses ATP to try to restore the concentration gradients

13. Voltage Gated channel

14. Endocytosis • No, its not a disease! • Use pinching and blebbing • Compartmentalization maintained • Fate once inside depends on what endocytosed

15. Receptor Mediated Endocytosis • Very specific • First step is binding event • Clathrin pits • Binding of receptor to ligand causes cytoplasmic change so receptor binds to clathrates • Causes clathrates to polymerize • Causes pinching in of vesicle • Fate depends on what brought in

16. Receptor Mediated Endocytosis

17. Clathrin Pits

18. Receptor - Mediated Signal Transduction • Binding event on receptor on outside of cell causes information to pass into cell • Hormone: Endocrine system responds to messages sent by nervous system and synthesizes chemical messengers off on

19. Signaling molecules may trigger • an immediate change in the metabolism of the cell (e.g., increased glycogenolysis when a liver cell detects adrenaline) • an immediate change in the electrical charge across the plasma membrane (e.g., the source of action potentials) • a change in the gene expression — transcription — within the nucleus. (These responses take more time.)

20. Second messengers • Often binding event (hormone on receptor) causes the formation of another molecule on the inside of the cell called secondary messengers • cAMP • Inositol • Ca2+ • Release causes cascade of events on inside

21. Hormones and G-Proteins

22. Hormone binding on outside Receptor is membrane bound G-proteins relay hormonal signal to other proteins by Phosphorylase Cascade Adenylate cyclase is activated: converts ATP to cAMP Release of c-AMP Activates cAMP dependent proteins in cell interior such as protein kinases Target enzyme either increases or decreases activity cAMP as a secondary messenger

23. Phosphorylase Cascade

24. Physiological Effects Communicated by cAMP

25. What is a popular habit-forming molecule and how does it affect cAMP? (hint…every morning!)

26. Caffeine • cAMP is regulated by the action of an enzyme: cAMP phosphodiesterase • Caffeine inhibits this enzyme and so cAMP remains active and its stimulatory effects too.

27. Ca2+ as a secondary messenger • Influences • Rates of lipids and glycogen degradation • Release of chemical transmitter in nerve cells • Muscle contraction • Beating of cilia and flagella • Involves binding protein called calmodulin • Ca2+ binds to Calmodulin causing conformational change • Active calmodulin binds to target enzyme

28. Phosphatidylinisitol 4,5 biphosphate (IP3) as a secondary messenger • G-proteins are activated by binding enzyme • Protein activates phospholipase C • The enzyme hydrolyzes phosphatidylinisitol 4,5 bisphosphate to IP3 • IP3 binds to Ca channel in ER causing Ca2+ to be released into cytosol.