Membrane Transport&Membrane Potential

Membranes and Transport

(Keeping the in in and the out out)

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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


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– Molecules moving with gradient– Osmosis– Uniport– Symport– antiport

• Facilitated– Uses carrier– Carnitine example


Active Transport

• 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

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

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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 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


What is a popular habit-forming 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.


Membrane Transport&Membrane Potential

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