1 - BM Flashcards
Is lipid composition the major determinant of membrane thickness? Transition temperature?
Membrane thickness - No, protein composition.
Transition temp - yes, lipid composition.
Membrane fluidity is dependent on these two factors? How?
Lipid composition - longer and more saturated -> higher transition temp
Temp:
low temp -> paracrystalline state
high temp ->liquid-disordered or fluid state
intermediate temp -> liquid-ordered state (little thermal motion in the acyl chains of bilayer)
How to equalize the concentration across the membrane?
- binding of substance to a macromolecule
- maintaining a membrane potential
- coupling transport to an exergonic proces
How to equalize the concentration across the membrane?
- binding of substance to a macromolecule
- maintaining a membrane potential
- coupling transport to an exergonic proces
Catalysis
required by transbilayer movement of lipids
3 types of lipid aggregates
- Micelles - formation depends on the temperature, mixture of lipids and ratio of lipids; impt in intestinal digestion and absorption of lipids
- Bilayer - two lipid monolayers/leaflets forming a 2D sheet, relatively unstable and spontaneously form liposomes
- Liposome - When bilayer folds back on itself to form vesicle; can entrap; used as drug carrier and vectors of gene therapy
Three common types of membrane receptors?
> GPCR
RTK
Ion channel receptors
What are the different solute transport processes? Limitations? Similarities?
- Passive Transport (Diffusion, Facilitated Diffusion)
- Limitations: thermal agitation, concentration gradient, solubility - Active Transport (Primary, Secondary)
Active and Facilitated Diffusion: > w/ specific binding sites > carrier is saturable > binding constant (Km) > structurally similar
Are ion channels selective for one ion?
Yes, highly selective but there are also a few which are nonselective.
What are aquaporins?
Water channels that function as tetramers of identical monomers
Membrane-microdomains of lipid protein complexes?
- Lipid rafts
- Caveolae
- Tight junctions
What are biological membranes?
- Covalent or non covalent assemblies?
- thermodynamically stable or not? How about metabolically?
Char: Highly fluid, dynamic viscous, plastic structures
Fxns:
- Divide cells into discrete compartments
- Define cellular boundaries
- Selective permeability (thus, maintaining differences from inside to outside of cell & free energy to be stored in concentration gradients)
- Establishes order
- Signal reception
- Regulate molecular traffic
- non covalent assemblies that are thermodynamically stable and metabolically active
- For cell recognition
- Maintain cell shape and locomotion
Fundamental properties of all biological membranes?
- Which is more dense -inner or outer layer?
- Movement of molecule based on permeability?
- Thickness and width of interface?
- What does it look like at xs?
- Dense inner layer than outer
- Dynamic
- Impermeable: most polar or charged
Permeable: non polar compounds - 7-10 nm thick; 1.5 nm interface
- Trilaminar
Basic structural unit of a biological membrane
Lipid bilayer
Major components of all membranes? Only organelle different?
Lipid and Proteins
> Inner mitochondrial membrane has higher protein component than lipid
Major lipids in mammalian membranes?
- Glycerophospholipids/Phosphoglycerides
- Sphingolipids
- Cholesterol
Structure of phosphoglycerides?
Glycerol molecule
+ phosphate esterified at the alpha-carbon
+ 2 long FA chains in ester linkages
+ Phosphorylated alcohol
*amphipathic
PPL are more abundant in which part of the membrane?
- Phosphatidylethanolamine
- -choline
- -serine
- -inositol
- Sphingomyelin
- Inner
- Outer
- Inner
- Inner
- Outer
Only membrane with more lipids than protein?
Myelin sheath
What are glycosphingolipids?
Sugar containing lipids built on a backbone of ceramide
Which phospholipid?
1. Major plasma membrane PPL in most cell types?
- Most variable PPL?
- Transfer of information from hormones and NTs across and found at the inner membrane
- Has net (-) which contributes to membrane potential; is important for binding
- Phosphatidylcholine
- Glycosphingolipids
- Phosphatidylinositol
- Phosphatidylserine
Sterols:
- Most common
- Location
- Characteristic
- Function
- Cholesterol
- Resides mainly at Plasma Membrane of mammalian cells
- Compact, rigid C8-branched HC chain attached to a D ring
- Reduces permeability and prevents packing up too closely
What is a glycocalyx?
CHO short (hydrophilic) chains at the ext surface of some proteins and lipids on the plasma membrane extending to the aq medium
Function: recognition molecules to protect cell from digestion and restricts uptake of hydrophobic compounds
Diffusion within the plane of membrane
Lateral diffusion
50% of the protein component in myelin? What is it?
Proteolipids
-hydrophobic lipoproteins soluble in Cf and mEtOH; insol in aq systems
Major lipoprotein in of brain myelin
Lipophilin
What maintains asymmety in membrane?
Lipid Transporters
Flippase vs Floppase vs. Scramblase
FlIppaSE
- Specific for PPLserine and PPLethanolamine;
- from extra to intra
- ATP dependent
FlOppase
- Not specific for PPL
- ATP dependent
Scramblase
- random; bidir
- nonspecific
- not ATP dependent. Instead, simulated by increase in intracellular calcium
Integral proteins are removable by what?
Detergents because they interfere with hydrophobic interactions
Integral Proteins
-General structure
-Bundle of alpha-helical transmembrane segment
Bonds associating peripheral proteins to membrane
Electrostatic interxn and H bonding with hydrophilic domains of IPs & polar head groups
Major determinant of transition temperature (solid -> semi solid)
Lipid composition
Membrane fluidity is dependent on
Lipid composition
-more saturated & longer = higher transition temp
Temp
-higher temp = ordered to disordered
At low temperature, lipids in a bilayer are in what form? At high temp? Intermediate?
Semisolid gel phase = PARACRYSTALLINE STATE; uniformly arrayed at surface and acyl chains are nearly motionless and packed with regular geometry
At high temp, liquid-disordered or fluid state
At intermediate temp, liquid-ordered state
Equalization of the concentration across the membrane can be circumvented by:
- Binding of substance to macromolecules
- Maintaining a membrane potential
- Coupling transport to an exergonic process
3 types of lipid aggregates
- Micelles
- Bilayer
- Liposome
Micelles
- Characteristics
- Function
- Formation depends on?
Micelles
- Amphipathic lipids that aggregate into spheres
- Important in intestinal digestion and absorption of lipids
- Formation depends on temperature and mixture & ratio of lipids
Bilayer
-Characteristics
- Formation
- Stability
- Two lipid monolayers forming a 2D sheet
- When xs areas of head group and acyl chain are similar
- Relatively unstable and spontaneously form liposomes
Liposomes
- Formation
- Function
Liposomes form when bilayer folds back on itself forming a hollow sphere -> vesicle -> liposome
Lose the hydrophobic edge achieving max stability
Function:
-Can entrap thus can be used as drug carriers and vectors of gene therapy
T or f. Some biological cells have no receptors.
f!!!!!
3 common types of membrane receptor proteins?
- GPCR
- RTK
- Ion channel receptors
What type of receptor?
- Glucagon
- Glutamate
- EPO
- Aminobutyric acid
- Acetylcholine
- Insulin
- GPCR
- Ion channel receptor
- RTK
- Ion channel receptor
- GPCR
- RTK
Limitations of passive transport? Why does this occur?
(1) Thermal agitation
(2) concentration gradient
(3) Solubility of solute
Occurs due to random thermal movement; with the concentration gradient
What is Vmax? Km? Which type of transport are they applicable?
Vmax = maximum rate of transport
Km = binding constant
Applicable for facilitated diffusion and active transport
Facilitated diffusion rate is dependent on which factors?
1 conc gradient
2 amount of carrier available
3 rapidity of solute carrier interaction
4 rapidity of conformational change for both loaded and unloaded carrier
How do hormones regulate facilitated diffusion?
By changing number of transporters available
Facilitated Diffusion vs. Active Transport vs. Simple Diffusion?
Simple Diffusion
-Happens to small or nonpolar particles
Faci Diff
- happens to large or polar particles
- can occur bidirectionally
Active
-unidirectional; against conc gradient
Uniport vs CoTransport?
Uniport
-moves 1 type of molecule bidirectionally
Co-Transport
-Transfer of system of one solute depends upon stoichiometric simultaneous or sequential transfer of another solute
Symport vs. Antiport
Symport
-moves 2 solutes in the same direction
Antiport
-moves 2 solutes in different direction
The specificity of channels and pores depend on?
Size and charge of the substance
Pore vs. Channel vs. Carrier
a. Conduit through membrane
b. Unitary event
a. Always Open - Intermittently open - never open
B. None (continuously open) - open/close - cycle of conformational changes
T or F. Ion channels are opened transiently and thus called gated.
T!!!
Water channels?
a. Name
b. Characteristic/structure
c. How does it exclude H3O+
A. Aquaporins <3
B. Functions as tetramers of identical monomers; Each monomer had 6 spanning helices that contain a conserved N terminal Asn-Pro-Ala (NPA)
C. By electrostatic repulsion due to presence of Arg at the constriction
Membrane-microdomains of lipid protein complexes?
- Lipid Rafts
- Caveolae
- Tight Junctions
What are lipid rafts? Function
Dynamic areas of exosplasmic leaflet of lipid bilayer enriched in cholesterol, sphingolipids, and certain proteins
Segregate and cluster increasing efficacy of signal transduction and other processes
Caveolae
- Derived from lipid rafts
- contains caveolin 1
- Flask shaped indentations of cell membranes
A special class of membrane rafts which consists of an integral membrane protein with 2 globular domains connected by a hairpin shaped hydrophobic domain which binds the protein to the cytoplasmic leaflet of the PM
Caveolin
Aka little caves which is responsible for signal transduction of insulin; membrane trafficking within cells and transduction of external signals into cellular responses
Caveolae
What are integrins
Heterodimeric proteins anchored to PM by a single hydrophobic transmembrane helix in each subunit
-Regulator of many processes e.g. platelet aggregation
Cross membrane movement of small molecules?
> Diffusion
> Active transport
Cross membrane movement of large molecules?
> Endocytosis
> Exocytosis
Signal transmission across membranes
> CSR (Signal transduction and signal internalization)
> Movement to intracellular receptors
Cell Transport of Macromolecules?
Endocytosis, Exocytosis, Phagocytosis, Pinocytosis
What is absorptive pinocytosis
Receptor mediated selective process primarily responsible with finite binding sites on PM
3 fates of molecules released by exocytosis
- Attach to the cell surface and become a peripheral protein
- Become part of ECM
- Can enter ECF and signal other cells
Classifications of Transporters
- ATPase
- ABC
- Solute Carrier Transport
ATPase
-Types
- E-type (involved in extracellular transport)
- F-type (for translocation of H in mitochondria)
- P-type (at PM)
- V-type (vacuoles and lysosomes)
4 steps in transport of solute molecules
- Recognition
- Translocation
- Release of substrate
- Recovery
Glut
Glut5
Glut - uniport from out to in; except erythrocyte glut (bidirectional)
Glut 5: prefers fructose
Where is this molecule more abundant?
Na, K, Ca, Mg, Cl, HCO3, PO4, Glucose, Protein
ECF - Na, Ca, Cl, HCO3, Glucose
ICF - K, Mg, PO4, Protein
Which compartment contains more water?
Intracellular contains 2/3 of TBW
Mutations of gene encoding AP-2
Nephrogenic Diabetes Insipidus
In Diptheria toxin, what is affected?
Ionophores
Mutation in gene encoding FGF3 receptor
Achondroplasia
Mutation in gene encoding LDL receptor
Familiar hypercholesterolemia
Abnormalities in CFTR protein and CI transport
Cystic fibrosis
Abnormalities in the ion channels of the heart
Congenital long QT syndrome
Copper dependent ATPase
Wilson’s Disease
Abnormalities in GlcNac phosphotransferase resulting in absence of Man-6-P signal for lysosomal localization of certain hydrolases
I cell disease
Abnormalities in spectrin and other structural proteins in RBC
Hereditary spherocytosis
Abnormalities in oligosaccharide chains of membrane glycoproteins and glycolipids
Metastasis
Deficiency in the attachment of GPI anchor to certain proteins of the RBC
Paroxysmal Nocturnal hemoglobinuria
