Membrane Structure and Transport of Small Molecules Flashcards
Lipid protein interactions
Noncovelent-can move in bilayer
Phosphoglycerides strucutre (3 names too)
Two fatty acid chains attached to to of three carbons of glycerol backbone
- one chain is nonsaturated-leading to kink-increases fluidity
- remaining hydroxyl attaches to phosphate, then to one of three head groups
- Usually no charge, unless serine is the head protein
phosphatidyl ehanoloamine, serine (negative), chline
Sphingolipds
Sphingosine backbone
- sphingomyelin
- fatty acid tail and phophocholine head group
Glyoclipids
Derived from sphingoseine with sugars added rather than phosphate
- asymmetric-sugar on external face of PM
- entry point for cholera toxin
- can be charged
Sterols
Polar OH-locaed near membrane surfaces (both leaflets)
- rigid sterol ring stiffens regions of membrane
- strengthens PM
Lipid hydropathy?
Amphipathic
- allows to form into a bilayer
- assuemble spontaneously
- micelle, or bilayer-keeping hydrophobic dry
- Try to keep as genetically favorable as possible
Lipid compostion
Depends on membrane type and cell type
- cholesterol and SM sit outside PM
- phoshphochoine/phosphotidylethanoloamine d structures are in intracellular membranes
- glycolipids in PM and inriched in myelin-little in internal membranes
Lipid movement
Diffuse between inner and outer layers but no flipping, also rotation occurs
-flipping creates and maintains assymetries
Assymetric distribution of leaflets
Innner-phosphodylethanolamineand phosho serine (negative)
Outer-sphingolipds, glycolipids, phospho choine
Cholestrol-roughly equal between leaflets
Lipid rats
Areas of non-random lipid distribution
- enricehd in cholesterol and sphingomyelin-thick structure that causes long SM chains
- sequesters subsets of membrane proteins
PI
Phosphotidlinositol-major role in cell signaling
- PIP3-serves as dock for downstream signaling molecules when they are soluble-precursor to IP3
- PIP3 can be cleaved and be active in cell signalling
Integral vs peripheral membrane proteins
Integral-incorporated into membrane with stretches of hydrophobic AA, either alpha helix of 15-20 aa or barrel with hydrophilic aa buried
-integral proteins have lipid covalently attached that can reversibly interact with membrane
Periperhal-associate with membrane via charge
Post translations that mediate association with membrane
Amide linkage, thioester linkage
Covalent attachment but is reversible and can be regulated
Cytoskeleotn and membrane proteins
Membrane proteins can diffuse within membrane-but are anchored to internal cytoskeleton
Small molecules/ions crossing PM rate
Hydrophobic easily go across
Small/large uncharged+polar go through very slowly
Ions never go through
Passive Transports
Channel mediated/Transporter mediated
- channlels are ion specific pores that open and close in regulated manner
- carriers-enzyme-like proteins that mediate passive transport down concentration gradient without chemical change
Active transport
Puumps-need energy, move against concentration gradient, ATP
Multiple of the same concentration gradients
Additive-potential can promote or oppose ion movements driven by concentration gradients-produce electrochemical gradient
Ion channels are critical to… by means of
muscle and nerve function
thousands of K+, N+, and Ca2+ channels
Types of carrier type transporters
Uniport-passive, transport down concentration gradient
symport/anticoupled
- sym-cotransported ion
- anti-something out, makes free for other to go in
Carrier uniporters transport
Oscillate between which side is open-whether or not solute bound
- solutes bind when oscillation occurs go in
- move down concentration gradient at higher rate than by diffusion
Na glucose symporter
Coupled carrier transport
Sodium binds, results in increase affinity for glusce, when both bind increase open and close rate
-both sites need to be occupied for conforation switch to occur
-allows transport of glucose against concentration gradient without direct energy expenditure
Polarity determination
By which receptor proteins are on top vs bottom
-nonrandom distribution of membrane proteins!
Transceullular glocose transport
- na down gradient dragging glucose inside-symporter-versus gradient
- Glucose down gradient through different transporter
Moves from digestive system, to epithelial, then out-down gradient-uniporter
Na/K pop towards EC-keep Na low in epithelial cell so system can work
Three classes of ATP driven pumps
Active transpot
Ptype=multpass TM domains
- autophosphorylate themselves with P from ATP
- Conformatinal change
- Pumps Ions
ABC transporter
-pumps small molecules (rather than ions)
Ca2+ ATPase
90% membrane protein in muscle cell
takes calcium from cyto-sequeesters in membrane space
- kinases bind ATP and can have specific AA phosphorylated=conformatinal change
- Ca enters bidning site-comes in , released into cell
- energy is from hydrolysis of ATP that leads to conformational change
Na+/K+ ATPase
Both transported against concentration gradient
1/3 of cellular energy used to maintain this pump
Na+ inside cell binds, phosphorylation, conformational change, Na+ transproted and released
K+ binds outide cell binds-dephosphorylation-induces another conformational change, K+ then enters cytoplasm and released
ABC transporters
ATP binding casettes
Two ATPase domains
- small molecule (ions) bonds to non-ATP bound state
- When ATP is bound, two ATPase binding domains can dimerize to produce conformation change that exposes substrate to opposite side of membrane for release
- ATP hydrolysis releases substrate, then prepares transporter for another round-conformational change when both ATP send the ion through
High levels of one type of ABC transporter
Multiple drug resistance
-allows more of hydrophobi drug to be cleared from cytoplasm
Chlorquine resistance (amiplifed transporter from malaria genome pumping drugs out)
ATP binding CFTR -drives opening and closing of Cl- channel-so an function as channel as well as transporter
