L6 Membranes And Membrane Transport

Front 1

What is the model of membrane structure?

Back 1

FLUID MOSAIC MODEL OF MEMBRANE STRUCTURE“Islands of protein in a sea of lipid

Front 2

What do membranes act as?

Back 2

Biological membranes act as selective permeabilitybarriers that block the passage of almost all water solublemolecules (into cells and organelles)

Front 3

Which molecules can move freely across the bilayer?

Back 3

Small uncharged or hydrophobic (lipid soluble) moleculescan freely traverse the bilayer by simple diffusion downtheir concentration gradients

Front 4

Which molecules require specialist proteins to move them across?

Back 4

Charged polar molecules require specialist proteins(pumps, transporters, pores) to carry them across themembrane

Front 5

What is the permeability of the lipid bilayer higher for?

Back 5

Permeability of lipid bilayer is higher for moleculesthat are uncharged, non-polar, and small

Front 6

Are the concentrations of the ions the same on either side of membranes?

Back 6

Concentrations of ions and charges are different on theinside and outside of cells

Front 7

What is an example of facilitated diffusion?

Back 7

Glucose(GLUT)

Front 8

What is an example of primary active transport?

Back 8

Na+/K+-ATPase

Front 9

What is an example of secondary active transport?

Back 9

Na+/Glucosetransporter(intestine)

Front 10

What is the normal concentration of Na inside and outside the cells?

Back 10

10nM and 140mM respectively

Front 11

What is the normal membrane potential?

Back 11

- inside and + outside

Front 12

What happens in SIMPLE / PASSIVE DIFFUSION?

Back 12

Solute moves from one side of the membrane tothe other along its concentration gradient

Front 13

What does the rate of diffusion depend on?

Back 13

Rate of diffusion depends on the octanol/waterPARTITION COEFFICIENT of the solute

Front 14

What is Kow

?

Back 14

Kow, the equilibrium constant for partitioning of amolecule between oil (octanol) and water

Front 15

What does the higher the value of Kow mean?

Back 15

The higher the value for Kow the more lipid soluble it is.

e.g. diethyl urea has a Kow = 0.01,urea has a Kow = 0.0002

Diethyl urea is 50 times more hydrophobic and travelsthrough a lipid bilayer 50 times faster than urea

Front 16

What is transmembrane movement of mineral ions mediated by?

Back 16

TRANSMEMBRANE MOVEMENT OF MINERAL IONS ANDHYDROPHILIC MOLECULES IS MEDIATED BY PROTEINS

e.g. ion channels, water channels (aquaporins)

Front 17

ION CHANNELS ARE USUALLY GATED. What can these gates be dependent on?

Back 17

Voltage-gated,

ligand-gated (extracellular, intracellular)

mechanically gated

Front 18

What does facilitated diffusion involve?

Back 18

FACILITATED DIFFUSION CAN INVOLVE A CONFORMATIONALCHANGE IN A SELECTIVE CARRIER PROTEIN

Front 19

What are the different transporters?

Back 19

UNIPORT, SYMPORT, ANTIPORT

Front 20

How do we distinguish between simple diffusion and carrier meditiated diffusion?

Back 20

The kinetics of transport distinguish between simplediffusion and carrier mediated transport

Front 21

What is the transporter affinity given by?

Back 21

Transporter affinity for substrate is given by the Km:The lower the Km the higher the affinity

Front 22

What is facilitated glucose transport mediated by?

Back 22

Facilitated glucose transport is mediated by a family of distincttransporters, which show sequence homology but tissue specificdistribution.

Front 23

What is the location of SLC2A1 / GLUT1?

Back 23

Ubiquitous;

Abundant in erythrocytes,low in skeletal muscle

Front 24

What does SLC2A1 / GLUT1 mediate?

Back 24

Mediates basal transport ofglucose to a wide range ofcells (Km ~ 1.8 mM)

Front 25

What is the location of SLC2A2 / GLUT2?

Back 25

Liver, Pancreatic ß-cells

Front 26

What are the features of SLC2A2 / GLUT2?

Back 26

Low affinity (Km ~ 20 mM) forglucose for compared toGLUT-1

Front 27

What is the location of SLC2A4 / GLUT4?

Back 27

Muscle, Adipocytes

Front 28

What are the features of GLUT4?

Back 28

Regulated by insulin (Km ~ 5mM)

Front 29

What are the glucose transporters overall?

Back 29

GLUT1: Low Km (high affinity). Mediates constitutiveglucose uptake in many tissues; Highly expressed inerythrocytes and blood-brain-barrier.

GLUT2: High Km (low affinity) and large Jmax (highcapacity). Transports glucose into hepatocytes andpancreatic ß-cells when [glucose]blood is high to regulateblood glucose levels.

GLUT4: Km similar to upper range of blood glucoseconcentrations. Found in muscle and adipocytes.Activity regulated by insulin, which recruits GLUT4 tothe plasma membrane.

GLUT3: Low Km (high affinity). Highest expression inneurons.

GLUT5: Fructose transporter

Front 30

What is ACTIVE TRANSPORT?

Back 30

MOVEMENT OF SOLUTE AGAINST THE CONCENTRATIONGRADIENT, THIS REQUIRES ENERGYPRIMARY – HYDROLYSIS OF ATPSECONDARY – ELECTROCHEMICAL GRADIENT

Front 31

What happens in the REGULATION OF GLUT4 BY INSULIN

Back 31

INSULIN Binds tomembrane receptor

Signals(phosphorylationcascade) tointracellular poolof GLUT4

Translocation ofGLUT4 tomembrane

WhenInsulinlevels fallGLUT4recycled topool

Front 32

What is PRIMARY ACTIVE TRANSPORT?

Back 32

Energy supplied by the hydrolysis of ATPATPADP + Pi

This drives energetically unfavourable biochemical processes

Na+/K+-ATPase in PLASMA MEMBRANE

H+-ATPase in LYSOSOMAL MEMBRANE

Ca2+-ATPase in PLASMA MEMBRANE ANDSARCOPLASMIC RETICULUM OF MUSCLE

Front 33

What happens in the Na+/K+-ATPase transporter?

Back 33

1. Na+ BINDS TO INTRACELLULAR SITE

2. THIS TRIGGERS AN AUTOPHOSPHORYLATION OF THEPUMP

Front 34

What happens when K+ binds inside the cell?

Back 34

1. PHOSPHORYLATION CAUSES A CONFORMATIONALCHANGE TO RELEASE Na+ TO THE EXTERIOR AND TO EXPOSEA K+ BINDING SITE

2. BINDING OF K+ TRIGGERS DEPHOSPHORYLATIONOF THE PUMP

PUMP RETURNS TO ORIGINAL CONFORMATION AND K+IS DISCHARGED INTO THE INTERIOR OF THE CELLWHOLE PROCESS ~10 ms

Front 35

What type of process is this?

Back 35

An “electrogenic” process

Front 36

How is the THE Na+/K+-ATPase IS A DRUG TARGET IN THETREATMENT OF CONGESTIVE HEART FAILURE?

Back 36

In the heart muscle, the Na+/Ca2+ antiporter (NCX) contributes toremoval Ca2+ from the cytosol allowing cardiac relaxation to occur.

1. Oubain inhibits the Na+/K+-ATPase by preventing K+ binding,decreasing the rate of Na+ extrusion from cardiac muscle cells.

2. This increases the intracellular [Na+], which reduces the activity ofNCX, resulting in slower Ca2+ efflux and therefore prolonged highcytosolic [Ca2+] to maintain cardiac muscle contraction.

Front 37

What happens in secondary active transport?

Back 37

UTILISATION OF AN ELECTROCHEMICAL GRADIENTe.g. Na+/Glucose Transporter (SGLUT1)

Front 38

What is secondary active transport important in?

Back 38

1. Intestinal epithelial cells for the absorption of dietary glucose

2. Epithelial cells in proximal tubules of the kidney for reabsorptionof glucose from the primary urine

Front 39

What is the cholera toxin?

Back 39

Cholera toxin, produced by Vibrio cholerae causes hugeelectrolyte and fluid losses in the intestine

Front 40

What is the process involved in the cholera toxin?

Back 40

1. Cholera toxin (CT) binds to theGM1 ganglioside receptor on theapical membrane of intestinal cells

2. CT is internalised by endocytosisand transported through the Golgito the ER

3. In the ER subunits of the toxin aresplit and the A1 subunit escapes tothe cytosol.

4. A1 binds to and overactivates theheterotrimeric GTPase Gsa,leading to an activation of AdenylylCyclase and an increase in cAMPlevels

5. This activates the CFTR Clchannelleading to large Clsecretion

6. Na+follows the electrical gradient

7. H2O follows the osmotic gradient

Front 41

What is the Role of the Na+/Glucose Cotransporter in ElectrolyteReplacement Therapy in Cholera?

Back 41

Replacement therapy includes ahigh concentration of glucose(~110 mM), which drives Na+(and consequently Cl- and H2O)back into the intestine throughthe Na+/glucose cotransporter(SGLUT)