Exocytosis – stuff out Endocytosis – stuff in Diffusion Fick’s Law of Diffusion F = j x a F is flow (mol/sec) j is flux (mol/sec/cm2) a is area (cm2) Molecules diffuse from high to low concentrations. Membrane Transport Four different types: -­‐ Simple diffusion -­‐ Passive transport (facilitated diffusion): o Channel-­‐mediated diffusion o Carrier-­‐mediated diffusion -­‐ Active Transport Nernst Equation Gives membrane For mammal cells: potential at equilibrium. V = -­‐61/z x log(x1)/(x2) Assumes only one ion is permeable. For reptilian cells: Units are mV V = -­‐58/z x log(x1)/(x2) If less inside then outside, ion will enter. X1 is inside conc. Osmosis Shrunk <-­‐> Normal <-­‐> Swollen <-­‐> Lysed 100mM NaCl = 200mOsmol/L Hypertonic <-­‐> Isotonic <-­‐> Hypotonic <-­‐> V. Hypotonic If more mOsmol/L inside then outside, water will diffuse into the cell. If more mOsmol/L outside then inside, water will diffuse out of the cell. Diffusion of urea into cells adds to the internal osmolarity so water follows the urea. Goldman Voltage Equation +
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K[K ]in + PNa[Na ]in + PCl[Cl ]out V = -­‐61 x log ( + + = ) PK[K ]out + PNa[Na ]out + PCl[Cl ]in Gives net effect of movement of many ions. If less inside then outside for positive ions, top line is in. If less inside for negative ions, top line is out. * Pores are conducts that are always open whereas channels are To get from current to flux/flow: conducts that are gated by a “door”. j = i/zFA * Cell membranes are permeable to lipid soluble molecules (O2). Simple diffusion Rate of Transport Rate of Transport Jmax Carrier-­‐mediated transport down conc. gradient Conc. Of Transported Molecules In simple diffusion there is no rate limit. Pores and channels increase permeability. Carrier mediated transport shows saturation and a rate limit. Facilitated diffusion is still powered by the energy in the conc. grad. but stops at equilibrium. Co-­‐Transport Some carriers facilitate the diffusion of more than one molecule. Co-­‐transporters are carriers that move several molecules in a fixed ratio. Eg. Na+-­‐Glu transporter moves 1 Glu for 1 Na+ This allows Glu to diffuse down Na+ conc. grad. Active Transport ATP powers movement through conformational change using phosphorylation. This allows substances to be pumped against their conc. grad. Active transport uses pumps. Equation – ATP <-­‐> ADP + PO43-­‐ Good example is the Na+K+ATPase pump à Which maintains low intracellular Na+ and high K+ by moving them against their conc. grad. using ATP. 3 Na+ out = 2 K+ in The phosphorylated conformation has high affinity for Na+ and low affinity for K+ when exposed to ICF. The dephosphorylated conformation has high affinity for K+ and low affinity for Na+ when exposed to ECF. Secondary Active Transport Gradients produced by a pump can be used to power movement of other substances eg Glu uptake in intestine. Primary active transport keeps Na+ low. Na+ linked to Glu entry on apical side. Na+grad powers Glu uptake into cell High Glu in cell powers facilitated diffusion Carrier on basolateral side moves Glu out. Release of Insulin Catalytic Receptors A kinase uses ATP to phosphorylate something. Five known types of catalytic receptors: 1. Receptor tyrosine kinase eg. insulin receptor (turned on by the ligand) 2. Tyrosine Kinase Associated Receptor (have the kinase as a separate subunit that binds the receptor) 3. Receptor serine/threonine kinase (phosphorylate target proteins on serine or threonine) 4. Receptor tyrosine phophotases (dephosphorylate target protein on a tyrosine) 5. Receptor guanylate cyclase (activated by NO, makes cGMP from GTP) Effects of Insulin -­‐
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increase Glu storage and oxidation increase protein synthesis decrease proteolysis increase triglyceride synthesis decrease lipolysis and lipid oxidation increase gene expression and growth signaling through protein phosphorylation modifies existing proteins and DNA transcription Protein Kinase B (PKB) Signaling Insulin Two major pathways: 1. through PI-­‐3P and PKB, activated glycogen synthesis and translocates GLUT4 glucose transporters to the cell membrane 2. Through MAPK, changing gene expression which alters the amount of an enzyme in a cell Lots of amplification. Slow to turn on, but long lasting effects