module 9 Flashcards
what are the membrane functions?
-separate cells from external environment: create unique intracellular environment
-allow selective transport of substrates in and out of cell
-provide location for specialized pathways and processes
-rapid changes in electric potential across the membranes of neurons
-localization of receptors to facilitate response to physiological signals
-mediate cell-to-cell recognition and interaction
membranes are: (membrane characteristics)
-sheet-like structures, two molecules thick, between compartments
-consist mainly of lipid and proteins, with carbohydrates linked to them
-build from amphipathic molecules
-impermeable to polar molecules (pretty much all biomolecules)
-self-assembling, non-covalent structures
-fluid and dynamic structures
-highly specialized in their composition and distribution (assymetric; outer and inner face)
specific membrane proteins mediate ______________
particular biological functions
what is the basic structural element of membranes?
LIPID BILAYER
-membrane formation is from amphipathic nature of the membrane lipid
-self-assemble through the hydrophobic effect
what causes membranes to have different structures?
the structure formed depends on the ratio of cross-sectional areas of the polar head group and the hydrophobic tai
-fatty acids favor micelle formation
-lipids with two hydrocarbons tails (glycerophospholipids and sphingolipids) tend to form bilayers
how do lipid bilayers form membrane vesicles?
-exposure of hydrophobic tails at the edge of the bilayer to water is energetically unfavorable
-flat bilayer sheets are unstable and spontaneously form membrane vesicles with an internal volume
-these vesicles are the basic of cells and organelles
what are membranes permable to?
-bilayers have a very low permeability to ions and most polar molecules
-permeability of small molecules is correlated with their relative solubility in water
-some small non-polar gases (O2 and CO2) and small hydrophobic molecules (like the fat soluble hormones) can pass directly through the membrane
-NOT WATER, use aquaporin
what are vesicles for drug delivery?
-cell membrane can represent a critical barrier for polar drugs intended for intracellular targets
-encapsulation of a drug within a liposome can facilitate transport across the membrane
-liposomes can also be used to target specific cells or organelles
why are ratios different from membrane to membrane?
-membranes are primarily composed of lipids and proteins
-more active membranes have a higher ration of protein to lipid
-composition of membrane components can be dynamic, in particular for prokaryotes
what is the fluid mosaic model?
SHOW FREEDOM OF LATERAL DIFFSUSION
-membranes are dynamic structures due to the nature of the non-covalent interactions
-lipids and proteins freely diffuse in the plane of the membrane
-lateral movement of proteins and lipids within the membrane is very rapid
-movement across the membrane is restricted
is the composition of the inner and outer sheets the same?
-lipid composition of the inner and outer sheets of the bilayer can be different, allowing for specialization of the membrane faces
transbilayer movement requires ________
CATALYSIS
how does transbilayer movement happen?
-requires a polar head group to pass through hydrophobic environment
-uncatalyzed rate of lipid molecule crossing from one sheet to the other (flip-flop diffusion) is very slow
-translocation of lipids from one side of bilayer to the other is catalyzed by enzymes called flippases
what is membrane fluidity? what are examples of composition
-cells need to maintain appropriate levels of membrane fluidity
cells can adjust membrane composition to maintain liquid-ordered state
-bacteria vary the length and saturation of the hydrocarbon tails of membrane lipids
-animals use cholesterol to mediate membrane fluidity
what are the phase transitions of membrane fluidity?
membranes undergo temperature-dependent phase transitions
-below the phase trans temp, membrane is too solid
-above the phase trans temp, membrane is too fluid
-at the phase trans temp, the hydrocarbon chains are partially ordered but lateral diffusion still possible (just right)
what is the table of examples of temperature-dependent changes to membrane composition
what is the specialization of membrane structure and function ?
-composition of membrane components: lipids and proteins
-distribution of membrane components: static and dynamic
-specialized membrane regions: lipid rafts
what are the specialized compositions of distribution of lipids in membranes?
-varies across species and cell types
-this include dynamic changes to composition and/or positioning to regulate biological events
-for example, the movement of phosphatidylserine to outer leaf functions in initiating cell destruction (apoptosis) (kills itself)
what do lipid rafts arise from?
-the spontaneous association of lipid molecules whose hydrocarbon tails are of similar length
what is an example of something that creates lipid rafts?
-sphingolipids (with longer tails) form clusters that exclude glycerophospholipids
-the longer, saturated hydrocarbons of sphingolipids form stable associations making the rafts thicker and more ordered than the rest of the membrane
what are lipid rafts?
-rafts are docking points in lipid-anchored proteins that contain long-chain saturated fatty acid anchors
-the lipid-linked proteins that associate with rafts often serve signaling functions
active roles of membranes often performed by __________
PROTEINS
-receptors and transporters
what are the three categories of membrane proteins? how are they defined?
defined based on different mechanisms of association with the membrane
-peripheral (c and d)
-lipid anchored (e)
-integral membrane proteins (a and b)
what are peripheral membrane proteins?
-associate with membrane through electrostatic or hydrogen-bonding interactions (easy to get off)
-can dock to either membrane lipids or integral proteins
-the bulk is in the cytosol or extracellular space
-changes in pH or ionic strength often release these proteins from the membrane
what are lipid-anchored membrane proteins?
-covalently attached lipids can anchor proteins to the membrane
-these protein modifications are sometimes reversible, allowing for regulation of cellular location
-GPI anchored proteins always at outer layer
-proteins with single chain hydrocarbons always to inner face
-diff fatty acid attach to diff part of the membrane (amino aicd)
what are integral membrane proteins?
-immersed in, and usually span, the membrane
-protein positioning withing a membrane is specific and directional
-tend to be of three varieties: single pass a-helical, a-helical bundles (7), and B-barrels
what is the distribution of amino acids in integral membrane proteins?
-blue=charged residues, mostly within the intra and extracellular portions of the protein
-white= residues with non-polar side chains, dominate inside the hydrophobic slab of the bilayer
-red=tryptophan
-orange=tyrosine
cluster at the interface between the hydrocarbon chain and polar head group region
how can we predict membrane spanning regions of integral proteins?
-predicted from the amino acid sequence
-stretch of 20 hydrophobic residues in a row are likely membrane spanning
-a hydropathy index look at the hydrophobic characteristics of a protein to predict transmembrane regions
-magnificent 7
what is hydrogen bonding within membrane-spanning regions?
-side chains within the transmembrane region tend to be non-polar, however the carbonyl and amid groups of each peptide bond are polar
-polar unpaired carbonyl and amide groups in the bilayer core are energetically unfavorable
-carbonyl and amide groups of the proteins backbone within the bilayer have to be hydrogen-bonded
what is the big graph of transport across membranes?
what is the table of transport across membranes?
what is simple diffusion?
-non-polar gases (O2 and CO2) and hydrophobic molecules can directly cross the membrane
-their direction and rate of movement is determined by their concentrations on either side of the membrane
-can only result in the net movement down a concentration gradient
what is facilitated diffusion?
-membrane transporters lower the activation energy barrier of crossing the bilayer
-activation energy for removing the hydration shell from a polar solute and transferring it into the non-polar environment in the core of the bilayer is very high
-membrane transporters lower the activations energy for crossing the membrane by replacing the hydration shell with interactions with polar groups along the transfer path in the protein interior
what are channels?
-membrane pores to transport molecules down concentration gradient
-high conductance rates because they bind the substrate very weakly
-do not saturate
what are carriers?
-membrane proteins that undergo substrate-induced conformational change, or membrane positioning, to release substrate to the other side of the membrane
-slower because they bind the substrate quite strongly
-can saturate
what is glucose permease of erythrocytes (red blood cells)?
facilitated diffusion through a carrier
-facilitated diffusion of glucose at 50,000X faster than simple diffusion
-specific for D-glucose
-the rate of uptake follows a pattern resembling M-M kinetics
-Kt about 1/3 the concentration of blood glucose so the transporter is nearly saturated and operates near V-max (75% of max capacity)
how is co-transport used in diffusion and secondary active?
-in diffusion, co-transport through antiport or symport depends on the charge of the molecules in order to have a net neutral change
-in secondary active co-transport, system couples a molecule moving down its gradient to one moving up its gradient
what is coupled transport?
-uniport=transport of a single molecules
-antiporters= move molecules in different directions
-symporters=move molecules in same direction
what is active transport?
-input of energy allows movement of molecules against concentration gradients
-primary active and secondary active
what is primary active transport?
-driven by direct source of energy (ATP)
-includes P-type, V-type and ABC transporters
what is secondary active transport?
-couples the movement of one molecules up its conc gradient within the movement of another molecule down its gradient
what is V-type ATPases?
vacuoles
-use the energy of ATP to move protons against a concentration gradient
-acidification of organelles
-in chloroplasts and mitochondria, F-type ATP synthases reverse this reaction to use proton gradient to generate ATP
what are ABC transports?
-contain ATP-binding domains (ATP-Binding-Cassette)
-transport a variety of biomolecules out of the cell against a concentration gradient
-multi-drug resistance protein pumps drugs (chemotherapeutic) out of the cell, rendering the drugs ineffective
-detoxifying system
what is P-type ATPase?
-Na, K ATPase uses the energy of ATP hydrolysis to pump three Na out of the cell and two K into the cell
-called a P-type transporter as it undergoes a phosphorylated intermediate
what is Na and K in the cell?
-cells maintain high gradients of Na outside the cell and K inside the cell
-this gradient controls cell volume, electrical excitability, and enables uptake of nutrients through secondary active transport systems
-maintaining the activity of Na K pump requires about a third of your energy
what is an example of secondary active transport?
-glucose uptake into intestinal epithelial cells
what is glucose uptake into intestinal epithelial cells?
-in intestinal epithelial cells, glucose uptake from the gut is driven through symport with Na
-the movement of glucose up its concentration gradient is enabled by the movement of Na ions down their concentration
-active transport of glucose from the gut depends on the action of the Na K ATPase to establish the gradient of Na ions
what are ion channels?
-enable rapid movement of ions across the membrane
-actions of ion channels can cause changes in membrane potential (action potentials) in neurons
-tightly regulated; voltage-gated channels and ligand-gated channels
-are highly selective for the molecule to be transported
ion channels differ from ion transporters (like Na, K ATPase) in three ways:
-faster
-no saturation limits
-gated/regulated (open and close in response to signal)
what is the specificity of ion channels (K channel)?
-K channels allows rapid movement of K ions out of cells
-although Na is smaller, the channel is 100-fold more permeable to K
-selectivity filter discriminates K and Na based on their ability to shed water molecules to form electrostatic interactions within backbone carbonyls
what is the speed of ion channels (K channel)?
-selectivity filter has four equivalent binding sites for K
-as K ions enter the filter, the electrostatic repulsion from other incoming K ions helps to push the flow of ions from inside to outside of the cell
