unit 15: Cell membranes Flashcards

1
Q

what are the functions of lipids in animals?

A

provide structure in cell membranes
energy storage
metabolites and messengers
enzyme cofactors
pigments (light retinal pigments, photosynthetic pigments)

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2
Q

what are the three main types of animal membrane lipids and their components?

A
  1. phospholipids (glycerophospholipids, sphingophospholipids)
  2. glycolipids (glycosphingolipids)
  3. sterols (cholesterol)
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3
Q

what are the general features of fatty acids

A
  • can have varying lengths of hydrocarbon chains w/ terminal COOH group
  • usually even number of carbon atoms in cellular fatty acids
  • can be saturated or unsaturated. and varying degrees of saturation
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4
Q

describe the general features of sterols

A
  • a 4 ring hydrocarbon structure w/ different hydrocarbon tails
  • has a OH- group (equivalent to a polar head group)
  • is only produced by eukaryotes
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5
Q

what are the main functions of membranes

A
  • enclose cell (plasma membrane)
  • intracellular compartmentalization (internal membranes in eukaryotes)
  • controls flow of molecules. between inside and outside of cell and intracellular compartments
  • ATP synthesis: occurs in plasma membrane of prokaryotes, inner mitochondrial membrane/chloroplast thylakoid membrane of eukaryotes
  • cell adhesion
  • cell communication/signaling
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6
Q

composition and fundamental architecture of cellular membranes

A
  • double-layered sheet like structures (leaflets) about 5-10 nm thick
  • composed mainly of lipids and proteins.
  • some carbohydrates can be attached
  • 1:4 to 4:1 lipid: protein ratio
  • non covalent assemblies of phospholipids stabilized by non covalent forces
  • asymmetric composition
  • electrically polarized. usually negative inside. the membrane potential is about 60mV
  • fluid mosaic model
  • dynamic
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7
Q

how do lipids interact with water and the forces contributing to formation of membranes

A
  • lipid bilayers form through self assembly of phospholipids via non covalent forces
  • driven by hydrophobic effect and van Der Waals forces b/w acyl chains
  • stabilized by interaction of hydrophilic head groups w/water. this is electrostatic interactions and hydrogen bonding
  • cooperative structures can be extensive
  • self healing structures: energetically unfavorable when planar. becomes energetically favorable when membranes fuse.
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8
Q

rank the permeability of gases, small uncharged polar molecules, large uncharged polar molecules, ions, charged polar molecules

A

gases - permeable
small uncharged polar molecules- slightly permeable
large uncharged polar molecules- impermeable
Ions- impermeable
charged polar molecules- impermeable

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9
Q

what are the categories of membrane proteins

A

peripheral membrane proteins
lipid-anchored proteins
integral membrane proteins

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10
Q

describe peripheral membrane proteins

A
  • electrostatic interaction and H-bonding w/polar head groups and other proteins
  • easily dissociated by ph, salt
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11
Q

describe integral membrane proteins

A
  • usually span membrane
  • hydrophobic domains interact w/hydrophobic core
  • hydrophilic domains interact w/surface
  • require detergents for disociation
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12
Q

describe lipid-anchored proteins

A
  • covalently attached hydrophobic chain provides membrane anchor
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13
Q

what are the different motifs found in membrane-spanning domains of integral membrane proteins

A
  1. single pass transmembrane protein
  2. multi pass transmembrane proteins
  3. beta strand transmembrane proteins
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14
Q

describe single pass transmembrane protein

A

a-helix
oligomerization by coiled-coil formation
hydrophobic amino acid side chains protrude from helix:
van der Waals interactions w/ lipids
peptide bonds toward interior of helix

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15
Q

describe multi pass transmembrane proteins

A
  • several a-helices
  • bacteriorhodopsin: proton pump, similar to eukaryotic G-coupled protein family, 7 membrane spanning helices connected by loops
  • eukaryotic aquaporins: facilitate diffusion of small hydrophilic molecules, half-helices form channel, tetramers w/ several membrane-spanning domains
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16
Q

describe b-strand transmembrane proteins

A

b-barrel motif formed by H-bonds between neighboring antiparallel beta-strands
- non polar residues outside
- polar residues line interior

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17
Q

describe a method for prediction of certain motifs

A

hydropathy plot:
- identifies segments w/hydrophobic amino acids from primary seq.
- plots free energy change for transferring 20 amino acid segments from hydrophobic to aqueous environment
- useful for predicting a-helical transmembrane domains

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18
Q

what effect do ionic detergents have on membrane proteins

A
  • bind to hydrophobic regions of proteins (membrane or soluble proteins)
  • denature proteins at high concentration
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19
Q

what effect do non-ionic detergents have on membrane proteins

A
  • milder non-denaturing
  • solubilize membrane proteins at low concentration
  • solubilize membranes by micelle formation at high concentration
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20
Q

define lipide/lipodomics

A

Complement of lipid-containing molecules of a cell/organ/tissue and its analysis

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21
Q

describe unsaturated fatty acids

A
  • cis configuration of double bonds in natural FA
  • double bonds are usually separated by one or more methylene groups in polyunsaturated fatty acids
  • have a lower melting point compared to saturated FA (ex. steric acid has a higher mp than oleic acid)
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22
Q

what are methylene groups

A

CH2

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23
Q

why are fatty acids a good source of energy?

A

they are highly reduced, more than carbs. so they are electron rich

  • this means they can provide a lot more energy than carbs
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24
Q

what do membrane lipids contain

A

polar head group and non polar tail

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25
Q

membrane lipids are___

A

amphiphilic, meaning they contain both polar and non polar portions

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26
Q

contrast phospholipids and glycolipids

A

phospholipids:
- contain a phosphate group
- can have a glycerophospholipids/phosphoglycerides or sphingolipid/ sphingophospholipid

glycolipids:
- contain a carbohydrate
- can have sphingolipid or galactolipid

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27
Q

describe glycerophospholipids

A

glycerol attached to
- 2 FA
- Phosphate - alchohol

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28
Q

describe sphingolipids

A

phospholipid:
sphingosine backbone
- 1 FA
- Phosphate - alcohol

glycolipid:
sphingosine backbone
- 1 FA
- carbohydrate portion

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29
Q

galactolipids

A

glycerol backbone
- 2 FA
- carbohydrate

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30
Q

describe phosphatidic acid

A
  • precursor glycerophospholipids/ Phosphogylcerides
  • is just the phosphate group, no alcohol bound
  • small amount found in membranes
  • glycerol backbone; C1 and C2 are ester to FA one usually has a cis double-bond. C3 ester bound to the phosphate group

in phosphoglycerides the phosphatidate is ester bound to an alcohol

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31
Q

what are common alcohols in glycerophospholipids and their charges once glycerophospholipids

A

serine (PS)- (-)
ethanolamine (PE)- 0, zwitterion
choline (PC) - 0, zwitterion
glycerol (Cardiolipin) - (-)
inositol (PI)- (-)

  • alcohol head group determines glycerophospholipid charge
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32
Q

where are PC, PE, and cardiolipin found

A

PE, PC- most abundant in eukaryotic membranes

Cardiolipin- mitochondrial inner membrane, bacterial membrane

33
Q

describe plasmogens

A

C1= ether bond to FA, and Ca double bonded to Cb

C2= ester linkage

fights against reactive oxygen species (ROS)
increased chemical stability
functional significance not well understood
abundant in nervous tissue
least abundant in liver

34
Q

describe ceramide

A
  • the sphingosine backbone
  • C18 amino alcohol molecule, with long unsaturated chain
  • FA linked by amide bond to C-2
35
Q

C1 in sphingolipids can be bond to?

A

phosphodiester bond to phosphate-alcohol= sphingophospholipids
- can be Phosphocholine or phosphoethanolamine

glycosidic bond to sugar= glycosphingolipids

36
Q

what are the subclasses of sphingolipids

A
  • sphingomyelins
  • glycosphingolipids
  • gangliosides
37
Q

describe sphingomyelins/phosphosphingolipids

A
  • head group is phosphocholine or phosphoethanolamine
  • found in plasma membranes of animal cells (eukaryotes)
  • lots in myelin
38
Q

describe glycosphingolipids / sphingosine derivatives (cerebrosides + Globosides)

A
  • head group is one or more sugars
  • sugar is always extracellular
  • used for cellular recognition (e.g blood groups)
  • neutral
  • cerebrosides: 1 sugar (can be glucose or galactose).
  • Globosides: 2 or more sugars.
39
Q

describe gangliosides

A
  • sphingosine derivative
  • several sugars with sialic acid
  • negative charged
40
Q

describe the clinical correlation of gangliosides with botulinum toxin

A
  • toxin binds to protein receptor and ganglioside for uptake
  • interferes with vesicle trafficking by blocking release of acetyl choline from motor neurons into synapsis
  • causes flaccid paralysis
41
Q

what do Amphiphilic/ amphipathic lipids do

A
  • Determine physical features of membrane (thickness, fluidity)
  • which determines barrier function
    (regarding molecules like polar and charged molecules)
42
Q

what do Membrane proteins do

A
  • give specific functions to membrane that determine transport and communication)
43
Q

what do free fatty acids and detergents form in water

44
Q

what do phospholipids and sphingolipids form in water

A

bilayers or liposomes

45
Q

what are the biological consequences of membranes

A
  • Closed compartments
  • Internal and external
    faces/leaflets
    cytosolic leaflet , exoplasmic leaflet
46
Q

define cytosolic and exoplasmic leaflet leaflet

A

cytosolic: it is found on the internal side of the plasma membrane, but the external side of organelles

exoplasmic: it is found the external side of the plasma membrane, but the internal side of organelles

47
Q

what happens to cytosolic and exoplasmic leaflets during budding and fusion (endocytosis and exocytosis)

A

they are persevered

48
Q

ways to study membranes

A
  1. generate liposomes or planar
    bilayers with different lipid composition
    • Can extract cellular membrane lipids with organic solvents
    • create synthetic lipids
  2. study Liposomes
    • study membrane features
    • include other molecules for use of transfection and drug delivery
  3. Planarbilayertostudymembrane
    permability
49
Q

rank according to increasing permeability
K+
Na+
Glucose
Cl-
indole
H20
Glycerol
Tryptophan
urea

A

Na+
K+
Cl-
Glucose
Tryptophan
urea and glycerol
indole
H20

50
Q

for small molecules, permeability depends on?

A

the solubility of the molecule in nonpolar solvent relative to its solubility in water

51
Q

what does Membrane crossing involve?

A

shedding water solvation shell
dissolving in hydrophobic core
diffusing through core
and becoming resolvated by water

52
Q

what are the motions of lipids within membranes

A
  • Rapid lateral diffusion
  • rotational motion
  • depend on fluidity

-Very slow transverse lipid diffusion (flip-flopping) *very unlikely if uncatalyzed
– Helps to preserve membrane asymmetry
– Catalyzed by translocases (flippase, floppase, scramblase)

53
Q

effect of heat on membrane fluidity

A
  • heat increases disorder
  • goes from gel-like or rigid to fluid like
54
Q

what are membranes at physiological ph

A

fluid like (disordered)

55
Q

how to quantify lateral motion of membrane components

A
  • use Fluorescence recovery after photobleaching (FRAP)
  • bleach area with laser beam
  • then measure the time it takes for fluorescence to recover
  • the bleached area is replaced with unbleached components by lateral diffusion
  • can be restricted b/c of tethering to other molecules
56
Q

factors that affect membrane fluidity

A
  • temperature
    phase-transition temp (melting temp) when membrane goes from solid like to fluid like
  • membrane composition
    fatty acid length
    fatty acid saturation
    cholesterol content
57
Q

what does fatty acid length do to membrane fluidity

A
  • longer FA decrease fluidity b/c more interactions
  • cis double bonds increase fluidity b/c less interactions
58
Q

how does cholesterol affect fluidity

A
  • more unsaturated FA. becomes stiffer. decreases fluidity
  • prevents crystallization at lower temps
  • in biological membranes with alot sphingolipids
59
Q

cholesterols correlation with spur cell anemia

A

-reduced fluidity of RBC b/c of high cholesterol content
- produces RBC with shortened life spans (acanthocytes)
- results in spur cell anemia
- caused by chronic liver disease, alcoholic cirrhosis

60
Q

how is membrane thickness affected

A
  • saturated FA increase thickness
  • Cholesterol increases thickness of membrane regions with a lot of phosphoglycerides
  • Cholesterol has no effect on thickness of membrane regions with a lot sphingomyelin (SM) or phospho- sphingolipids
61
Q

how is membrane curvature affected

A
  • by lipid shape
  • More curvature with cone-shaped lipids (PE) vs. cylinder-shaped (PC)
  • inserted proteins
62
Q

why is membrane curvature important

A
  • for membrane budding and vesicle formation
63
Q

describe membrane lipid asymmetry

A

exotoplasmic side
- Glycolipids
- Cholin-containing lipids (PC, SM)

cytosolic side
- NH2-group-containing lipids (PS, PE), and PI (negative charge)

Cholesterol evenly distributed in both leaflets

64
Q

what are the consequences of membrane asymmetry

A

Affects membrane curvature
– Less fluid outer leaflet with SM, PC
– More fluid inner leaflet with PI, PE, PS
– natural curvature

Mediates cell signaling
– Phospholipid cleavage by
Phospholipase C
– PI Phosphorylation by PI Kinases
– Platelet aggregation (PS)
– Detecting apoptotic cells by externalized PS

65
Q

describe membrane raft domains

A
  • Microdomains with a lot of SM, cholesterol and certain glycolipids
  • thicker and less fluid than sea domains
  • a lot in certain membrane proteins (lipid- or GPI-anchored)
  • Identified by resistance to detergents
66
Q

do membrane protein content vary in different membranes? most abundant?

A

yes; in mitochondria

67
Q

protein composition is…

A

cell-type specific

68
Q

proteins mediate all membrane functions except?

A

the barrier
* mediate transport and signal transduction/communication

69
Q

what are the types of lipid-anchored proteins

A
  • Long-chain Fatty Acids
  • Isoprenoids
  • GPI-anchor
70
Q

describe lipid-anchored protein: long-chain fatty acids

A

Palmitate, myristoate
* Linked by amide bond to N-terminal gly or thioester bond to internal cys

71
Q

describe lipid-anchored protein: isoprenoids

A
  • Prenyl group
  • Linked by thioether bond to C-terminal cysteine
  • Often second group linked to internal cysteine
72
Q

describe lipid-anchored protein: GPI- anchor

A
  • Glycolipid with PI linked to C-terminus
  • Always extracellular
73
Q

describe membrane carbs

A

Bound to proteins and membrane lipids
- most transmembrane proteins are glycosylated

  • on the exoplasmic side
  • Creates protective coating on
    cells (glycocalix)
  • Prevents inappropriate cell-cell interaction
74
Q

how to solubilize lipids and membrane proteins

A
  • detergents (for lipids and integral membrane proteins)
75
Q

detergents are what type of molecules

A

amphiphatic

76
Q

describe detergents

A
  • can be Ionic and non-ionic detergents
    – Can get into bilayer and disrupt forces
    – Water-soluble at low concentration
    – Form micelles at higher concentration
77
Q

which of the following are ionic detergents and which are non ionic:

A. sodium deoxycholate
B. Sodium dodecylsulfate (SDS)
C. Triton X-100
D. Octylglucoside

A

ionic: A,B
non ionic: C,D

78
Q

What do ionic detergents do vs. non ionic detergents

A

ionic detergents:
– Bind to hydrophobic regions of proteins (membrane or soluble proteins)
– Denature proteins at high concentration

non ionic:
– Milder, i.e. non-denaturing
– Solubilize membrane proteins at low concentration
– Solubilize membranes by micelle formation at high concentration