Download membranes and transport

Membranes and Transport
(Keeping the in in and the out out)
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
Lipid Structures In water
Fluid Mosaic Model of Cell
Membranes
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
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
Transport across the membrane
• Moving particles
– Diffusion
• Simple
• Facilitated
– Active Transport
– Endocytosis
– Receptor mediated endocytosis
• Moving information
– Signal transduction
Diffusion
• With concentration gradient
– Swimming downstream
• Simple
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Molecules moving with gradient
Osmosis
Uniport
Symport
antiport
• Facilitated
– Uses carrier
– Carnitine example
Active Transport
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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
Active Transport
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.
Voltage Gated Channels
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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
Voltage Gated channel
Endocytosis
• No, its not a disease!
• Use pinching and
blebbing
– Compartmentalization
maintained
– Fate once inside depends
on what endocytosed
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
Receptor Mediated Endocytosis
Clathrin Pits
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
Signaling molecules may trigger
1. an immediate change in the metabolism of the
cell (e.g., increased glycogenolysis when a liver
cell detects adrenaline)
2. an immediate change in the electrical charge
across the plasma membrane (e.g., the source
of action potentials)
3. a change in the gene expression — transcription
— within the nucleus. (These responses take
more time.)
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
Hormones and G-Proteins
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
Phosphorylase Cascade
Physiological Effects Communicated by
cAMP
Epinephrine
Glucagon
Skeletal muscle
Glycogen
degradation
Adipose tissue
Triacylglycerol
degradation
Heart
Increased heart rate
Intestine
Fluid secretion
Smooth muscle
Relaxation: (Ca2+)
Liver
Glycogen
degradation
Blood platelets
Inhibition of secretion
Adipose
Decreased
triacylglycerol
degradation
What is a popular habitforming molecule and how
does it affect cAMP?
(hint…every morning!)
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.
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
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.