1. Chapter 9 (part 3) Membranes

2. Membrane transport Membranes are selectively permeable barriers Hydrophobic uncharged small molecules can freely diffuse across membranes. Membranes are impermeable to polar and charged molecules. Polar and charged molecules require transport proteins to cross membranes (translocators, permeases, carriers)

3. Transport of non-polar molecules Non-polar gases, lipids, drugs etc… Enter and leave cells through diffusion. Move from side with high concentration to side of lower concentration. Diffusion depends on concentration gradient. Diffusion down concentration gradient is spontaneous process (-  G).

5. Transport of polar or charged compounds Involves three different types of integral membrane proteins 1.Channels and Pores 2.Passive transporters 3.Active transporters Transporters differ in kinetic and energy requirements

6. Channels and Pores Have central passage that allows molecules cross the membrane. Can cross in either direction by diffusing down concentration gradient. Solutes of appropriate size and charge can use same pore. Rate of diffusion is not saturable. No energy input required

7. Porins Present in bacteria plasma membrane and outer membrane of mitochondria Weakly selective, act as sieves Permanently open 30-50 kD in size exclusion limits 600-6000 Most arrange in membrane as trimers

8. Passive Transport (Facilitated Diffusion) Solutes only move in the thermodynamically favored direction But proteins may "facilitate" transport, increasing the rates of transport Two important distinguishing features: –solute flows only in the favored direction –transport displays saturation kinetics

9. Three types of transporters Uniporter – carries single molecule across membrane Symport – cotransports two different molecules in same direction across membrane Antiport – cotransports two different molecules in opposite directions across membrane.

10. Saturation Kinetics of transport Rate of diffusion is saturable. K tr = [S] when rate of transport is ½ maximun rate. Similar to M-M kinetics The lower the K tr the higher the affinity for substrate.

11. Transporters undergo conformational change upon substrate binding Allows substrate to transverse membrane Once substrate is released, transported returns to origninal conformation.

12. Active Transport Systems Some transport occur such that solutes flow against thermodynamic potential Energy input drives transport Energy source and transport machinery are "coupled" Like passive transport systems active transporters are saturable

13. Primary active transport Powered by direct source of energy(ATP, Light, concentration gradient) Secondary active transport Powered by ion concentration gradient. Transport of solute “A” is couple with the downhill transport of solute “B”. Solute “B” is concnetrated by primary active transport.

14. Na + -K + ATPase Maintains intracellular Na low and K high Crucial for all organs, but especially for neural tissue and the brain ATP hydrolysis drives Na out and K in

15. Na + -K + ATPase Na + & K + concentration gradients are maintained by Na + -K + ATPase ATP driven antiportsystem. imports two K + and exports three Na + for every ATP hydrolyzed Each Na + -K + ATPase can hydrolyze 100 ATPs per minute (~1/3 of total energy consumption of cell) Na + & K + concentration gradients used for 2 o active transport of glucose in the intestines

16. 1 o active transport of Na+ 2 o active transport of glucose

17. Transduction of extracellular signals Cell Membranes have specific receptors that allow cell to respond to external chemical stimuli. Hormone – molecules that are active at a distance. Produced in one cell, active in another. Neurotransmitters – substances involved in the transmission of nerve impulse at synapses. Growth factors – proteins that regulate cell proliferation and differentiation.

18. External stimuli(first messenger) – (hormone, etc…) Membrane receptor – binds external stimuli Transducer – membrane protein that passes signal to effector enzyme Effector enzyme – generates an intracellular second messenger Second messenger – small diffusible molecule that carrier signal to ultimate destination

19. G-Proteins Signal transducers. Three subunits, (  )  and  anchored to membrane via fatty acid and prenyl group Catalyze hydrolysis of GTP to GDP. GDP bound form is inactive/GTP bound form active When hormone bound receptor complex interacts with G-protein, GDP leaves and GTP binds. Once GTP -> GDP G-protein inactive GTP hydrolysis occurs slowly (kcat= 3min -1 ) good timing mechanism

20. Epinephrine signaling pathway Epinephrine regulation of glycogen degradation Fight or Flight response Ephinephrine primary messenger G-protein mediated response. G-protein activates Adenyl-cyclase to produce cAMP cAMP is the second messenger Activates protein kinase Activates glycogen phosphorylase

22. Effect of Caffeine Caffeine inhibits cAMP phosphodiesterase, prevents breakdown of cAMP. Prolongs and intensifies Epinephrine effect.

23. Phosphatidylinositol (PI) Signaling Pathway G-protein mediated G-protein activates phospholipase C (PLC) PLC cleaves PI to form inositol- triphosphate (IP 3 ) and diacylglycerol (DAG) both act as 2 nd messengers IP 3 stimulates Ca 2+ releases from ER DAG stimulates Protein kinase C