Chapter 9 (part 3)

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Chapter 9 (part 3)

• Membranes

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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)

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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 (-DG).

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Transport of polar or charged compounds

• Involves three different types of integral
  membrane proteins
• Channels and Pores
• Passive transporters
• Active transporters
• Transporters differ in kinetic and energy
  requirements

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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

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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

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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

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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.

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• Rate of diffusion is saturable.
• Ktr S when rate of transport is ½ maximun
  rate.
• Similar to M-M kinetics
• The lower the Ktr the higher the affinity for
  substrate.

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

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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

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• 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.

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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

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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 2o
  active transport of glucose in the intestines

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

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• 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

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G-Proteins

• Signal transducers.
• Three subunits, (a,b, g) a and g 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 -gt GDP G-protein inactive
• GTP hydrolysis occurs slowly (kcat 3min-1) good
  timing mechanism

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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

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Effect of Caffeine

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

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Phosphatidylinositol (PI) Signaling Pathway

• G-protein mediated
• G-protein activates phospholipase C (PLC)
• PLC cleaves PI to form inositol-triphosphate
  (IP3) and diacylglycerol (DAG) both act as 2nd
  messengers
• IP3 stimulates Ca2 releases from ER
• DAG stimulates Protein kinase C

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