Membranes and transport

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MEMBRANES AND TRANSPORT

• M.Prasad Naidu
• MSc Medical Biochemistry, Ph.D,.

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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

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Lipid Structures In water
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Fluid Mosaic Model of Cell Membranes
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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

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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

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Transport across the membrane

• Moving particles
• Diffusion
• Simple
• Facilitated
• Active Transport
• Endocytosis
• Receptor mediated endocytosis
• Moving information
• Signal transduction

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Diffusion

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

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Active Transport

• Requires Energy in the form of ATP
• Against concentration gradient
• Example Na/Kpump
• Enzyme is Na-K-ATPase
• 3 Na ions move in 2 K ions move out

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Active Transport
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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.

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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

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Voltage Gated channel
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Endocytosis

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

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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

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Receptor Mediated Endocytosis
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Clathrin Pits
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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
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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.)

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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

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Hormones and G-Proteins
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cAMP as a secondary messenger

• 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

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Phosphorylase Cascade
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Physiological Effects Communicated by cAMP
Epinephrine Skeletal muscle Glycogen degradation
Adipose tissue Triacylglycerol degradation
Heart Increased heart rate
Intestine Fluid secretion
Smooth muscle Relaxation (Ca2)
Glucagon Liver Glycogen degradation
Blood platelets Inhibition of secretion
Adipose Decreased triacylglycerol degradation
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What is a popular habit-forming molecule and how
does it affect cAMP?

• (hintevery morning!)

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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.

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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

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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.

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