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2011-09-24 21:29:16
lipids biochemistry

MS1/Mod 2: Biochemistry; lipids
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  1. Sphingolipids
    sphingomyelin (SP), gangliosides
  2. glyceryl phospholipids
    phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylserine (PS), phospatidylinositol (PI), cardiolipin (CL)
  3. amphipathic molecules
    • phosphoglyceride
    • sphingomyelin
    • archaeal lipid
  4. How are lipid bilayers considered to be formed by self-assembly?
    • 1. structure of LB is inherent in structure of constituent molecules
    • 2. growth is rapid and spontaneous in aq sln
  5. How are LB considered to be cooperative?
    • 1. many non-covalent interactions
    • 2. no edges w/ hydrocarbons next to water...compartmentalization is favored
    • 3. self-sealing (hole unfavorable)
  6. chem forces in LB
    • 1. phobic-primary interaction; btw tails
    • 2. VdW-btw tails; favors close packing
    • 3. electrostatic-leads to H bonds btw polar heads and water
  7. liposome
    LB used for drug delivery; fuses directly w/ PM of target cell so contents are delivered directly and bypasses circulation and digestive system; not v selective unless target signals exploited
  8. integral membrane prot
    require detergent or organic solv to stabilize
  9. peripheral mem prot
    interact w/ integral mem prot or w/ polar head groups of lipids

    solubilized by mild cdns (high ionic strength)
  10. alpha helices in BL
    i.e. bacteriorhodopsin

    most common structural motif for mem spanning regions of prot; composed of phobic AA but has loops w/ philic AA that extend in cytoplasmic and exoplasmic aq env
  11. beta sheets in BL
    i.e. bacterial porin

    phobic AA on outside of pore (touching tails); philic AA line center of pore to make an aq env
  12. prostaglandin H2 synthase-1
    ex of integral mem prot that does not span entire lipid bilayer; dimerization leads to formation of phobic channel in the mem
  13. significance of prostaglandin H2 synthase-1
    dimerization forms a phobic channel in the LB: prostaglandin's subst is arachadonic acid which is phobic; arachadonic acid does not have to leave the phobic env of the LB to find prostaglandin AS

    arachadonic: generated by hydrolysis of lipids; why in BL mem to start w/
  14. Aspirin
    inhibits prostaglandin synthesis by transferring acetyl group to Ser 530 of prostaglandin channel; blocks subst access to AS

    note: Ser is polar AA in polar channel of nonpolar BL
  15. peripheral mem and phobic groups
    prot that are normally soluble are attached to peripheral mem prot through cov interaction
  16. S-palmitoylcysteine
    peripheral mem prot covalently attached to phobic groups through cysteine
  17. C-terminal S-farnesylcysteine methyl ester
    peripheral mem prot covalently attached to phobic groups through cysteine
  18. glycosyl phosphatidyl inositol (GPI) anchor
    peripheral mem prot covalently attached to phobic groups through C terminus
  19. phase transition
    facilitates lateral diffusion of prot
  20. Tm
    temp at which half of lipid mol are solid and half are fluid
  21. rate of diffusion
    proportional to mol diffusion coefficient and conc grad

    rate ~ D x (Cside1/Cside2)
  22. diffusion coefficient (D)
    func of lipid solubility of mol; philic mol diffuse slowly and phobic mol diffuse rapidly
  23. concentration gradient (Cside1/Cside2)
    diff in conc across mem
  24. diffusion across mem
    • occurs from area of higher conc to area of lower conc
    • the greater the conc diff, the greater the rate of diff
  25. sm lipophilic mol
    • use simple diffusion
    • 1. sheds its solvation shell of water
    • 2. dissolves in the hydrocarbon core of the mem
    • 3. diffuses through core to other side of mem along conc grad
    • 4. resolvated by water on other side
  26. passive transport
    does not require E; aka facilitated diffusion
  27. acetylcholine receptor
    • l'esempio di facilitate diffusion and ligand gated channels
    • transports Na and K ions along conc grad in response to neuronal signals
  28. active transport
    goes in opp direction as conc grad; requires E
  29. Na-K pump
    • l'esempio di active transport
    • exchanges Na and K against their conc grad using ATP hydrolysis; essential for synaptic transmission
  30. Na channel
    voltage gated passive transport
  31. AChR
    ligand gated passive transport; allows Na and K down their grad once 2 Ach bind to receptor
  32. Cl- channel
    cAMP regulated passive transport
  33. Pressure sensitive
    passive transport
  34. glucose transporter
    transporter passive transport
  35. Na/K pump
    primary ATPase active transport
  36. respiratory chain ligand
    primary redox coupled active transport
  37. multidrug resistance protein transporter
    ATP binding cassette active transport
  38. Na dep glucose transport
    secondary active transport
  39. primary active transport
    ATP hydrolysis moves mol against its conc grad
  40. secondary active transport
    grad of mol X established by primary active transport; mvmt of X back into cell down its conc grad provides energy to drive co-transport of second mol, S, against its conc grad
  41. uniport
    transports a mol in one direction
  42. symport
    cotransport of two mol in same direction
  43. antiport
    cotransport of 2 mol in opp directions
  44. mvmt of uncharged mol energetics
    • G=RTln(Cside2/Cside1)
    • G changes as a func of concentration ratio; linear relationship
  45. mvmt of mol w/ charge energetics
    G=RTln(Cside2/Cside1) + ZFV

    • F=faraday
    • V=potential in volts across mem
    • Z=charge

    G changes as a func of mem pot; linear relationship
  46. Sarcoplasmic reticulum Ca ATPase
    uniporter; primary active transport

    transports Ca against its conc grad using E of ATP hydrolysis; against conc grad bc going into sER where there is already buttloads of Ca
  47. Na-Glucose symporter
    basolateral side of epithelial cells, symporter; secondary active transport (mvmt allowed by Na/K ATPase)

    transports gluc against its conc grad using downhill flow of Na along its conc grad (from grad set up by Na/K pump)
  48. K voltage gated channel
    uniporter; passive transport; voltage gated ion channel
  49. selectivity for K in K (voltage gated) channel
    once pore becomes too small, K must shed its outer layer of water in order to fit through

    achieved by AA in pore-K can interact w/ TVGYG w/in 3 angstrom diameter pore (other ions are too small or too large to fit through)
  50. "ball and chain" mechanism
    inactivation domain-positively charged ball (tethered by chain domain to channel)

    • closed state: bal is located in cytosol (not yet depolarized from AP)
    • open state: depolarization from AP opens channel and allows for neg binding site for pos ball
    • inactive state: pos ball moves into neg binding site and blocks channel
  51. ionophores
    • drugs that can be used to disrupt ionic grad in microorganisms
    • surround ions and shuttle them across mem
  52. potent toxins
    cmpds that collapse ionic grad (w/o ionic APs and no transport of anything)
  53. valinomycin
    sm, cyclic ionophore that disrupts K gradients by binding K and carrying it across mem
  54. monensin
    ionophore that disrupts Na gradients