Membrane Structure + Synthesis Flashcards
Features of membrane?
Flexible Self-sealing Selectively permeable Define external boundaries Divide internal space
eg of polar head group?
Choline, Serine, Ethanolamine, Inositol
Define membrane asymmetry
cytosolic side of membrane diff from ECF side
What’s the distribution of Sphingomyelin (SM)?
phospholipid where glycerol replaced by sphingosine Present in myelin. Exoplasmic
What’s the distribution of Phosphatidylcholine (PC)?
head group is choline. Exoplasmic
What’s the distribution of Phosphatidylserine (PS)?
in healthy cell. Cytosolic
What’s the distribution of Phosphatidylethanolamine (PE)?
Cytosolic
What’s the distribution of Phosphatidylinositol (Pl)?
minor involved in intercellular signal transduction. Cytosolic
What’s the distribution of Cholesterol (Cl)?
equally
What factors affect fluidity?
temp, FA composition, chain length, degree + extent of saturation, cholesterol content
How does saturated fatty acyl chains affect fluidity?
increased rigidity as they pack closer together so stronger interactions
How does chain length affect fluidity?
increased rigidity as increased interactions
How does cholesterol hydroxyl group affect fluidity?
forms H bonds w phospholipids the hydrophobic tail disrupts the regular interaction between fatty acyl chains
How does low temp affect fluidity?
Low energy of molecules, so decreased motility of membrane (molecules closer together) but cholesterol (in small numbers) interferes w interaction between phospholipids to increase fluidity
How does high temp affect fluidity?
High energy of molecules, so increased motility of membrane (molecules far) but cholesterol (in high numbers) stabilises membrane by bringing phospholipids closer together to decrease fluidity
How does spur cell anaemia affect fluidity?
increased cholesterol by 25-65% decreases membrane fluidity –> spikey 🔴 which are fragile + obstructive
Why is transverse diffusion slower than lateral diffusion?
requires 3 enzymes
takes energy getting hydrophilic head via fatty membrane
Role of Floppase?
moves phospholipids from inner to outer leaflet, requires ATP
Role of Flippase (flipase)?
moves phospholipids from outer to inner leaflet, requires ATP
Role of Scamblase?
bidirectional movement
Describe membrane synthesis of lipids
- enzymes in cytosolic ER
- as new lipids inserted, bilayer starts to bow as one side enlarged
- newly synthesized lipids move to luminal side by flippase so both sides enlarged
Why would the synthesis of ER lipids be altered?
membranes flow from ER to golgi to vesicles (Except sphingomyelin + glycolipids start in ER to golgi)
What’s apoptosis?
Cells that want programmed cell death display eat me signals for macrophages on their plasma membrane. Marker is Phosphatidylserineis inside of membrane but undergo transverse diffusion when needed so exposed on surface
What are the major lipid classes?
phospholipids, glycolipids, cholesterol
Features of integral membrane proteins?
- Single or multi pass
- Strong non-covalent bonds
- Trans-membrane domain often an α-helix
- can be predicted from sequence
- interact extensively w lipid bilayer
Features of peripheral membrane proteins?
- on the extracellullar or cytosolic membrane
- associated by non-covalent bonds
- interact w integral proteins or lipid polar head groups
Features of lipid anchored membrane proteins?
Covalently linked to lipid molecule (glycero-phosphatidylinositol)
Features of membrane carbohydrates?
- Carb associated w membrane lipids + proteins
- Form 2-10% of membrane weight
- Carb faces away from cytosol
- Involved in cell-cell interactions or cellular recognition
- 8% of 🔴 weight
Function of plasma membrane?
barrier, transport, signal transduction
Function of mitochindria membrane?
barrier, E transduction
Function of RER + SER membrane?
translation, complex lipid synthesis
Function of golgi membrane?
post-transational modification, processing for secretion
Function of nuclear membrane?
attachment of chromatin
Function of lysosome membrane?
hydrolytic enzymes
Function of peroxisome membrane?
FA oxidation
Chemical composition of myelin membrane?
protein 18%
lipid 79%
carb 3%
Chemical composition of erythrocyte membrane?
protein 49%
lipid 43%
carb 8%
Chemical composition of hepatocyte membrane?
protein 54%
lipid 39%
carb 7%
Chemical composition of outer mitochondrial membrane?
protein 50%
lipid 46%
carb 4%
Chemical composition of inner mitochondrial membrane?
protein 75%
lipid 23%
carb 2%
Which molecules can pass via simple diffusion?
lipid soluble molecules : N2, O2
small uncharged polar molecules : Urea, H2O, glycerol, CO2
Which molecules can’t pass via simple diffusion?
large uncharged polar molecules : Glucose
ions : H+, Na+, HCO3-, K+, Ca2+, Cl-, Mg2+
What’s a uniporter?
transports single type of substrate species across membrane, active/passive
What’s an antiporter?
moving 2 molecules in opposite directions
What’s an symporter?
moving 2 molecules in same direction
What’s co-transport?
when transporter moves 2 molecules simultaneously
can be antiporter or symporter
What does a low Kt value?
shows affinity of transporter for glucose
HIGHER affinity - readily bind to glucose
Describe GLUT1
in all mammalian tissues for basal glucose uptake
Kt = 1mM
Describe GLUT2
in liver to remove excess glucose from blood
in pancreatic β cells for regulation of insulin
Kt = 15-20mM
Describe GLUT3
in all mammalian tissues for basal glucose uptake
Kt = 1mM
Describe GLUT4
in muscle plasma membrane + adipocytes for increasing endurance training
Kt = 5mM
Describe GLUT5
in small intestine for fructose transport
How glucose transporter works?
- transporter binds to glucose
- conformational change : opens inner portion to cytoplasm so glucose diffuses in
- glucose is phosphorylated as it enters to maintain conc grad
How glucose transporter works?
- transporter binds to glucose
- conformational change : opens inner portion to cytoplasm so glucose diffuses in
- glucose is phosphorylated as it enters to maintain conc grad
How can glucose uptake be increased + eg?
increasing the number of transporters
GLUT4 in adipocytes + muscle stimulated by insulin
Features of facilitative transport AT?
selective + needs integral membrane protein
Features of facilitative transport AT?
selective
needs integral membrane protein
Sodium linked to antiport system w potassium using Na+/K+ATPase pumps 3Na+ out for every 2K+ in
Describe facilitative diffusion
- transporter binds to glucpse
- conformational changes
- opens inner portion to cytoplasm
- glucose diffuses in
- transport
- driven by conc grad
- bidirectional transport
- gradient maintained by phosphorylation
What are the kinetics of glucose transport?
-Transporter specific for molecules they transport (D-glucose, not L-glucose)
-Interactions exhibit saturation type
kinetics (plateaus) + can be regulated
-
What’s glucose transport increased by?
increasing number of transporters on cell surface
eg GLUT4 in adipocytes + skeletal muscle stimulated by insulin
eg of AT?
[Na] outside cell is 140mM is higher than inside 15mM but no free movement as they cannot get through membrane so requires integral membrane protein
eg of antiporter?
Na/K ATPase
How does Na/K ATPase work?
Requires ATP, pumps 3Na+ out for every 2K+ in which establishes conc gradient between inside + outside
What’s foxglove?
- Contains chemical digitalis (a cardio tonic steroid which inhibits the Na/K pump)
- Increases force of contraction of heart, so is treatment for congestive heart disease
- Inhibits pump leading to increased intracellular Na+ which leads to slower removal of Ca2+ by Na/Ca exchanger so increased ability of the muscle to contract.
Sodium dependent glucose transporters?
SGLUT-1 + SGLUT-2
How do SGLUT-1 + SGLUT-2 work?
- Sodium dependent glucose transporters
- Symporters only work if both Na + glucose bound then both transported into cell (passive)
Why’s SGLUT-1 + SGLUT-2 indirectly active process?
glucose phosphorylated while Na pumped actively out by Na/K ATPase to maintain the Na conc gradient
Describe cellular asymmetry
- Allows transport of molecules
- SGLUT-1 (Na+ driven glucose symporter) is on gut lumen side of enterocyte + transports glucose from lower to higher conc using conc gradient of Na+
- GLUT-2 on basal domain of cell transports glucose down its conc gradient (from higher in cell to lower in ECF)
- Na/K ATPase pump also works down here
Role of oral rehydration therapy?
Targets co-transport of glucose + Na for replenishment of sodium + water losses by ORT (or IV infusion)
Describe oral rehydration therapy
-fluid from body entersintestinallumenduringdigestion
-fluid isisosmoticwith blood + contains high Na(142
mEq/L)
-healthy individual secretes 2000–3000 mg of Na daily into intestinal lumen
-all reabsorbed so Na remain constant
-diarrheal illness, sodium-rich intestinal secretions lost before reabsorbed
-dehydrationorelectrolyte imbalanceswithin hours when severe fluid loss
How are transport proteins associated with disease?
Chloride channel mutation (CTFR) causes cystic fibrosis
protein involved in multi drug resistance pumps out small molecules
1 in 20 caucasians carriers of single deletion at position 508, if carry deletion in both copies, gene produce a
protein that fails to insert into membrane
Key facts about membrane?
Membranes act as semi-permeable barriers
Transport across them may be passive or active
ATP production is dependent on the properties of membranes
Cystic fibrosis is a disease of transport across membranes
Role of compartmentalization?
Separates reactions
Enables local environment to be regulated eg pH
Brings reactants together
How do these proteins get to correct compartment/organelle?
signal sequences which target them to specific organelles.
can also target a protein to a diff location by changing the signal sequence
Describe disease of misdirection
- Not all proteins targeted using their AA seq since lysosomal enzymes targeted by carbohydrate mannose-6 phosphate
- If deficient in a phosphotransferase present in golgi, then cannot modify mannose normally present on enzymes targeted to for lysosomal enzymes, they appear in blood + urine
Why are diseases caused by inability of cell to target the
enzyme to the lysosome?
-Lysosomes acidic environment due to proton pump that pumps H+ into lysosome
-Lots of transporters/enzymes associated with inner
mitochondrial membrane
What are membrane carbohydrates involved in + eg?
- Cell recognition eg blood antigens which are glycolipids, lymphocyte trafficking down blood vessel wall by selectins – requires a type of glycoprotein
- Glycolipids the carbohydrate is almost the same just on modification which is dependent on the expression or not of specific glycosyltransferases
