M&R 1 Flashcards
Name the 3 main types of lipid:
1) Phospholipids
2) Sphingolipids
3) Cholesterol
Where in a cell are phospholipids synthesised?
Endoplasmic Reticulum
Give an example of a phospholipid:
Phosphatidylcholine
Phosphatidylserine
Phosphatidylinositol etc
What are the 2 types of sphingolipids?
1) Sphingomyelin
2) Glycolipids
What name is given to the type of sphingolipid which has a sugar monomer head group?
Cerebroside
What name is given to the type of sphingolipid which has an oligosaccharide head group?
Ganglioside
How can cholesterol increase the integrity and decrease the fluidity of a membrane?
Its rigid planar conjugated ring closely associates with the nearest fatty acid chain of a phospholipid, reducing aliphatic tail mobility
How can cholesterol decrease the integrity and increase the fluidity of a membrane?
Its rigid planar conjugated ring intercalates between phospholipids, separating them, preventing crystallisation
Approximately what percentage of a membrane is cholesterol?
~45-50%
What are the 4 possible mobility modes of a phospholipid in a bilayer?
1) Lateral diffusion
2) Flip-flop
3) Rotation
4) Flexion
What mode of phospholipid mobility is rare, and why?
Flip-flop
Thermodynamically unfavourable
What is an integral membrane protein?
A membrane protein which has 1+ transmembrane domains, and interacts with both the hydrophobic and hydrophilic domains of the bilayer
What are the possible ways a membrane protein can interact with the hydrophobic region of the bilayer?
- alpha-helix insertion from the cytoplasmic side
- fatty acid post translational modification
What is used to remove integral membrane proteins for the lipid bilayer?
- Solvents
- Detergents
What is the average length (in amino acid residues) of a transmembrane domain?
~ 18-22 amino acids
What are peripheral membrane proteins?
Proteins associated with the hydrophilic domain of a bilayer
What forces bind a peripheral membrane protein to a bilayer?
Electrostatic forces
Hydrogen bonds
Disulphide bridges
What are the 3 types of mobility of an integral membrane protein?
1) Fast lateral diffusion
2) Fast axial rotation
3) Conformation changes
Name the transmembrane glycoproteins which anchor ribosomes onto the endoplasmic reticulum:
Ribophorins
What is the average length of the signal sequence of an integral membrane protein, and what particle recognises this?
~ 18-30 amino acids
SRP = Signal Recognition Particle
Via which complex does integral membrane protein synthesis occur through, to enter the ER?
Peptide Translocation Complex
What are the main properties of a stop transfer signal?
- Highly hydrophobic
- 18-20 amino acids long
Which enzymes cleave signal sequences?
Signal peptidases
Why is membrane asymmetry of proteins so important?
Proteins must face the direction of the signal to complete its function.
Ex: A receptor for an extracellular messenger MUST face the ECM
How do unsaturated fatty acids affect membrane fluidity?
Unsaturated fatty acids have a double bond, creating a kink in their structure, which reduces packing and prevents crystallisation
What is a Band 3 anion exchanger?
Cl-/HCO3- exchanger on the plasma membrane
What is Glycophorin A, and on what cell type is it expressed?
It is an antibody
Erythrocyte membranes
What is the function of Ankyrin, and in what cell type it is expressed?
It attaches the spectrin-actin cytoskeleton to integral membrane proteins
Erythrocytes
Which proteins form the alpha2/beta2 heterotetramer meshwork of the erythrocyte cytoskeleton?
- Spectrin
- Actin
What is the role of Band 4.1 in an erythrocyte?
Stabilises spectrin-actin interaction
What kind of interaction does Band 4.1 make with an erythrocyte membrane?
It is a peripheral membrane protein, so interacts with the interior hydrophilic domain of the bilayer
What kind of interaction does Ankyrin make with an erythrocyte membrane?
It is a peripheral membrane protein, so interacts with the interior hydrophilic domain of the bilayer
What kind of interaction does Glycophorin A make with an erythrocyte membrane?
It is an integral membrane protein, so interacts with both the hydrophilic and hydrophobic domains of the membrane bilayer.
What kind of interaction does Band 3 anion exchanger make with the erythrocyte membrane?
It is an integral membrane protein, so interacts with both the hydrophilic and hydrophobic domains of the membrane bilayer.
Name 2 peripheral erythrocyte membrane proteins which bind the spectrin-actin cytoskeleton to intergral membrane proteins:
1) Ankyrin
2) Band 4.1
To which integral membrane protein does Ankyrin bind to?
Band 3 anion exchanger
To which integral membrane protein does Band 4.1 bind to?
Glycophorin A
How does hereditary spherocytosis cause anaemia?
- Mutation causes reduced expression of spectrin by ~ 40-50%
- Deformed cytoskeleton causes cell to round up, and cannot change shape to pass through capillaries without lysing
- Reduced number of circulating red blood cells
What is the name of the condition in which expression of spectrin is reduced by ~ 40-50%?
Hereditary Spherocytosis
How does hereditary elliptocytosis cause anaemia?
- Mutation causes defective spectrin formation
- Cannot form heterotetramer with Actin
- Deformed cytoskeleton prevents cell from regaining its bi-concave shape after becoming elliptoid through capillaries
- Trapped and lysed by spleen
- Reduced number of circulating red blood cells
What is the name of the condition which prevents the formation of the spectrin-actin heterotetramer?
Hereditary elliptocytosis
Name 4 molecules which can freely diffuse across a biological membrane:
O2 CO2 N2 H2O Benzene Ethanol Urea Glycerol Fat-soluble vitamins (ADEK)
Name 4 atoms/molecules which cannot freely diffuse across a biological membrane:
Glucose Sucrose Na+ Ca2+ K+ Mg2+ H+ Cl- HCO3-
What does the rate of passive diffusion depend on?
- Concentration gradient
- Permeability of the membrane
What does the rate of facilitated diffusion depend on?
- Number of transport proteins available
- Temperature
Define active transport:
Transport against an unfavourable concentration and/or electrical gradient, using energy directly or indirectly from ATP hydrolysis
What is the difference between primary and secondary active transport?
Primary active transport uses energy directly from ATP hydrolysis
Secondary active transport uses energy indirectly from ATP hydrolysis (uses mvt of 1 molecule to drive another)
Name the 2 types of primary active transporters:
1) ATPase ion transporters
2) ATP-binding cassette transporters
Name the 3 types of ATPase ion transporters:
1) P-type
2) F-type
3) V-type
Generally, how does a P-type ATPase ion transporter function?
- ATP hydrolysis causes phosphorylation of the transporter
- Causes conformational change
- Ion channel opens/closes
Give an example of a P-type ATPase ion transporter:
Na+/K+ ATPase pump
What are the subunits of the NA+/K+ ATPase pump, and what are their functions?
alpha subunit: contains the ligand- and nucleotide- binding sites
beta subunit: directs channel to the plasma membrane from the endoplasmic reticulum
gamma subunit: anchors the channel within the plasma membrane
Name 4 molecules which can bind to the alpha subunit of the Na+/K+ ATPase pump:
Na+
K+
ATP
Ouabain
What type of ATPase ion transporter sets up and maintains the pH gradient between the ICM and ECM?
V-type ATPase
ie H+-ATPase
What is the role of a V-type ATPase?
Set up and maintain the pH gradient between the ICM and ECM
What type of ATPase ion transporter uses the H+ gradient for ATP synthesis?
F-type (ATP synthase)
What is the role of an F-type ATPase ion transporter?
Uses the H+ gradient to drive ATP synthesis
Name an F-type ATPase ion transporter:
ATP synthase
What type of ATPase ion transporter does Ouabain bind to?
P-type : Na+/K+ ATPase pump
What is the pH of the exctracellular fluid?
~ 7.4
What is the pH of the cytosol?
~ 7.1
What is the pH within mitochondria?
~ 7.7
What is the pH within a lysosome?
~ 4.6-6
What is the pH within secretory vesicles?
~ 5-6
In which cell component does pH = 7.7?
Mitochondria
What is the [Ca2+] of the extracellular fluid?
~ 2mM
What is the [Ca2+] of the cytosol?
~ 10-100 nm
Name the 2 types of secondary active transporters:
1) Symporters
2) Antiporters
What type of transporter is the Na+/Ca2+ exchanger?
Secondary active transporter (antiporter)
What are the 4 types of stimuli which may open channel proteins?
- Mechanical stretch
- Extracellular messengers
- Intracellular messengers
- Membrane voltage
Name the 3 ion proteins which are most important in regulating [Ca2+] inside a cell:
1) PMCA (Plasma Membrane Ca2+ ATPase)
2) SERCA (Sarco- and Endo-plasmic Reticulum Ca2+ ATPase)
3) NCX (Na+/Ca2+ Exchanger)
Which Ca2+ channel(s) have high affinity but low capacity for Ca2+?
- PMCA (Plasma Membrane Ca2+ ATPase)
- SERCA (Sarco- and Endo-plasmic Reticulum Ca2+ ATPase)
Which Ca2+ channel(s) have low affinity but high capacity for Ca2+?
NCX (Na+/Ca2+ Exchanger)
Which Ca2+ channel removes most of the Ca2+ from a cell after muscle contraction? Why?
NCX (Na+/Ca2+ Exchanger)
It has a much higher capacity for Ca2+ transport, compared to the other Ca2+ channels
Why does the intracellular [Ca2+] increase during ischaemia?
- Glycolysis stops due to lack of O2
- ATP levels are depleted
- Na+/K+ ATPase stops due to lack of ATP
- Intracellular [Na+] increases
- NCX reverses, extruding Na+ from the cell, but bringing Ca2+ into the cell, increasing the [Ca2+]i
How does glucose enter the apical side of intestinal epithelial cells? What ion channel is this mechanism dependent on?
Na+-Glucose cotransporter
Dependent on Na+/K+ ATPase
Name 4 types of acid extruders:
- V-type H+-ATPase
- Na+/H+ exchanger
- Cl-/HCO3- exchanger
- NA+/HCO3- cotransporter
Name 2 types of base extruders:
- Band 3 anion exchanger (Cl-/HCO3-)
- Na+/HCO3- cotransporter
Which channel in the ascending limb of the loop of Henle is blocked via loop diuretics?
NKCC
Na+/K+/Cl2- Cotransporter
What type of diuretic blocks the Na+/K+/Cl2 cotransporter in the ascending limb of the loop of Henle?
Loop diuretic
In what part of the kidney does a Loop diuretic work?
Ascending limb of the loop of Henle
What channel is blocked in the distal convoluted tubule of the kidney via Thiazide diuretics?
NCCT
Na+/Cl2- Co-transporter
What type of diuretic blocks the Na+/Cl2- cotransporter in the distal convoluted tubule of the kidney?
Thiazide diuretic
In what part of the kidney does a Thiazide diuretic work?
Distal convoluted tubule
What channel is blocked in the Cortical Collecting Duct of the kidney via Amiloride?
ENaC
Epithelial Na+ Channels
What type of diuretic blocks the Epithelial Na+ Channels in the cortical collecting ducts of the kidney?
Amiloride
In what part of the kidney does Amiloride work?
Cortical collecting duct
Name 3 types of diuretics:
Loop diuretics
Spironolactane
Amiloride
Thiazine
Which diuretic inhibits Aldosterone action at the kidney?
Spironolactone