Ch 9: Lipids & Biological Membranes Flashcards
lipids
biological molecules soluble in organic solvents
fatty acid
carboxylic acid (polar head) with long-chain hydrocarbon side groups (nonpolar tail)
Saturated
- only single bonds
- flexible (rotation)
- tightly packed (large # of weak intermolecular forces—Van der Waals + hydrophobic effect)
- melting point increases with molecular mass
no db/triple bonds in saturated fats excluding…
polar head
fats are harder to melt as you increase length of chain bc?
bc it is more stable
is it easier to make even or odd numbered fatty acids?
even
unsaturated
- contain double bond
- rigid, cis configuration
- lose packing, reduced interactions
- lower melting points
- delta 9 = db bond at 9th carbon from carb. acid
the more weak interactions contributing to something…
the stronger the overall forces of that
triacylglycerols
- another form of lipids
- energy reservoirs in animals
- 2-3 diff types of fatty acids
- yield more energy bc less oxidized than carbs
- also provides warmth (animals)
less oxidized…
… yield more energy per mass unit
Fats and oils
complex mixtures of triacylglycerols
triacylglycerols: 2-3 diff types of fatty acids
name by adding -oyl to end of each fatty acid and ending with “glycerol”
adipocytes
- provide energy (2-3 months)
- synthesize triacylglycerols
glycerol
attach all fatty acids to hydroxyl groups
trans fat consumption
- db bonds in unsaturated acids oxidized to aldehydes & carboxylates
- hydrogenated to reduce some of the db bonds
- side effect: convert cis to trans
- causes cardiovascular disease (increase consumption of trans fat, increase of cholesterol)
trans conformation
- have issues digesting this
- increases melting pt as u can pack molecules tightly
- increases Van der Waal interactions
glycerophospholipids
- modification of triacylglycerols
- bind to active site, fatty acid tail hangs out
- aka phosphoglycerides
- amphiphilic
- phosphatidic acid
glycerophospholipids: phosphoglycerides
C1 & C2 esterfied with fatty acids, C3 contains phosphate
glycerophospholipids: amphiphilic
- nonpolar aliphatic tails & polar phosphoryl-x heads
- x can be sugars, AAs, hydrogen, etc.
glycerophospholipids: phosphatidic acid
- X is H
- saturated C16 or C18 at C1 position
- unsaturated C16 to C20 at C2 position
phospholipases
- enzymes that hydrolyze glycerophospholipids
- can disrupt membranes (detergents & in venoms)
- selectively cleaves carbon 2
- use destruction of these as a signal
plasmalogens
- special type of glycerophospholipids
- contain ether linkage
- “X” = Serin, ethylamine
- easily oxidized
react w/ free radical that are naturally produced by metabolism, to prevent damage to other molecules
“sacrificial limbs”
sphingolipids
- membrane component
- amino alcohol derivatives; most derived from C18 amino alcohol sphingosine
- no ester linkages
sphingolipids: ceramide
N-acyl fatty acid derivative of sphingosine
sphingolipids: sphingomyelins
bear phosphocholine or phosphoethanolamine group
sphingolipids: cerebrosides
ceramide w/ single sugar head group
sphingolipids: gangliosides
ceramides with attached oligosaccharides
phosphocholine & phosphoethanolamine
most common sphingolipids that occur in plasma membranes
Steroids
- another form of lipids (eukaryotes), things like cholesterol + hormones
- 4 fused, nonpolar rings
- steroid hormones
steroid hormones
- glucocorticoids
- mineralocorticoids
- androgens & estrogens
glucocorticoids
affect carbohydrate, protein, and lipid metabolism
mineralocorticoids
regulate salt/water excretion
androgens and estrogens
sexual development and function
isoprenoids
- other lipids
- build from 5C units that resemble isoprene
—- Ubiquinone (coenzyme Q—major player in cell respiration as it acts as e carrier in mitochondria)
fat soluble vitamins
- vitamin A
- vitamin K
- vitamin E
- long carbon chains = nonpolar
vitamin A
(retinol)
- derived from plant products like Beta-carotene, part of vision process
- deficiency = blindness
vitamin K
- involved in blood clotting
- excessive bleeding & easy bruising
vitamin E
- group of compounds, prevents oxidative damage
- big group of compounds…needs to be monitored
Vitamin D
- vitamin D1 & D2 —-inactive forms
- active vitamin D promotes intestinal absorption of Ca2+
- water insoluble, can accumulate in fatty tissue
Vitamin D2
- R = Y (ergocalciferol)
vitamin D3
- R = X (cholecalciferol)
cholesterol
- most abundant protein
- tail will change
- OH group makes cholesterol slightly polar
- does better in inorganic solvents
Lipid bilayer formation
- driven by hydrophobic effect
—–size constraints - made up of phosphoglycerides & sphingolipids
hydrophobic effect
not an attraction b/t non polars but exclusion of non-polar tails by water to maximize entropy
liposome
closed, self-sealing solvent filled vesicles bounded by single bilayer
Lipid bilayer: fluidlike properties
- layers are not static (are moving)
- transverse/flip-flopping of lipids is rare (thermodynamic barrier)
- lateral diffusion (movement w/in the same plane)
- constant rotation around C-C bond of lipid tails
——-polar heads nestle in next to each other
transverse diffusion (flip-flop)
- takes massive amnts of energy
- won’t see polar heads flip-flop, but move up & down
lateral diffusion
- moves in same plane
- most likely to happen
- rapid
lipid bilayer: fluidity temperature dependent
- HIGHLY DEPENDENT
- above transition temperature = liquid crystal
——-organized liquid, still have bilayer but a lot of space (movement allowed) - below, gel-like solid
cholesterol decreases membrane what?
- membrane fluidity
- by getting into spaces b/t fatty acids = motion restricted
how do animals regulate the fluidity of its cells?
by changing the types of lipids that are in it
membrane proteins
- integral (intrinsic) proteins
- asymmetrically oriented amphiphiles
- transmembrane
- glycophorin A
integral (intrinsic) proteins
- associated tightly w membrane via hydrophobic interactions
- anchors
asymmetrically oriented amphiphiles
larger side & smaller side
transmembrane proteins
spans both faces of membrane
glycophorin A
- 3 domains: inside, outside, bilayer interacting portions
- help segregate diff parts of membrane
How to completely disrupt membrane/extract integral proteins?
use a detergent
lipid bilayer: structure
- indicative of the type of protein
- hydrophobic portions interact with lipid bilayer
- shield polar backbone
- alpha-helices common structure (taller than width of mem + common way we see integral proteins sit in mem)
shield polar backbone
- helices w/ nonpolar residues
- nonpolar AAs as part that spans membrane = protection
lipid bilayer: structure (pt 2)
- hydrophobic portions interact w lipid bilayer tails
- shield polar backbone
- Beta-barrel possible (to form channels thru bilayer)
- porins = channel-forming proteins
Lipid linked proteins
- lipid acts as anchor (not like integral proteins)
- prenylated = built from isoprene (isoprene = decorate/identify proteins)
- Cys-X-X-Y
- linked to Cys S atom (thioether + most common way to connect to mem)
- intercellular membranes & cytoplasmic face of plasma membrane
Cys-X-X-Y
- X = often aliphatic amino acid
- Y = Ala, Met, Ser (farnesylated)
OR - Y = Leu (geranylgeranylated)
Lipid linked proteins: fatty acylated
- 2 common ways: myristic acid & palmitic acid
fatty acylated: myristic acid
(C14, saturated)
- amide linkage, thioester
- myristylation stable for life
- located cytosol, ER, inner face of plasma membrane & nucleus
- plays nice, high melt. pt., no rotational restrictions, packs tight
fatty acylated: palmitic acid
(C16, saturated)
- amide linkage, thioester
- palmitoylation reversible, regulates
- located only cytoplasmic face of plasma membrane
—–where we need to regulate which proteins are sitting on membrane
lipid linked proteins: glycophosphatidylinositol-linked (GPI-linked)
- located on exterior face of plasma membrane
- protein attaches at C terminal (n-terminus is free)
fatty acids will vary based off?
protein we’re trying to attach to
peripheral membranes
- aka extrinsic
- bind to membrane via electrostatic & hydrogen bonding
- easiest to dissociate from mem
- still important (cytochrome C)
membrane structure
fluid mosaic model- membrane is not static, proteins can be imbedded
- constant movement
fluid mosaic model
- fluorescence recovery after photobleaching (FRAP)
photobleaching
put sm energy/light into fluorescent molecule “essentially turns it off”
defining cell shape
- sub membranous (inside mem) network of proteins as membrane skeleton (proteins under mem)
- certain things will be anchored/immobile
- spectrin
- ankyrin
- gate & fences model (herding sheep)
spectrin
- protein that provides membrane skeleton of erythrocytes (dense, triple stranded alpha helical coil coils)
ankyrin
- binds integral membrane ion channel protein
- anchor mem skeleton to membrane
membrane lipids
- asymmetrically distributed (will find one type of lipid in one leaflet vs the other more frequently)
- carb tail interior of mem, polar head exterior membrane
- synthesized on cytoplasmic face of mem (inner leaflet)
- flip-flop to get to correct side
flip-flop
- conformational change, push lipid thru enzyme
- flippase
- phospholipid translocase
- new membrane created from expanding existing membranes
flippase
- enzyme, catalyzes outer to inner leaflet flip of lipid
- anchored in mem
phospholipid translocase
- transport specific phospholipids across a bilayer
- LOW TO HIGH CON
- “taking it up”
- enzyme itself will move across bilayer then release it when it’s on other side
floppase
- opp fucntion of flippase
- catalyzes inner to outer leaflet
scramblase
- do it in either direction
lipid rafts
- small, closely packed glycosphingolipids & cholesterol (lil thicker, less fluid like)
- glycosphingolipids associate laterally via weak interactions of head group, cholesterol fills the gaps
- expedite the process?
secretory pathway
- pathway of proteins from ribosomes thru rough ER mem. embedded into matrix
- an assembly of complex structure made of multiple enzymes & activated by GTP in order to get protein embedded in membrane
- harvest energy from cleavage of phos. groups from GTP to drive this process
translocon
- pore/hollow cylinder that we can send things through
- transmembrane channel facilitates protein transport thru ER reticulum and into lipid bilayer
—– alpha, beta, gamma subunits (10,1, and 1 TM alpha- helices respectively)
—– small helix blocks entry acting as plug to prevent unwanted leaking of other small mol
—— soluble proteins move enter channel
——- transmembrane proteins enter channel, alpha helix opens to lipid bilayer releasing into lipid bilayer
main function = create soluble conduit for polar protein to move thru
Intracellular vesicle transport
- translation (syn of polypep. from an mRNA transcript from ribosome)
- golgi where posttranslational modifications made
- transportation thru golgi
movement is progressive
transportation thru golgi
- anterograde transport
—- move from backfold (closest to ER) to the end furthest away from ER - cisternal progression (maturation)
—– when ur going thru golgi parts (change & mature into next type)
transportation coated vesicle
- membrane secretory & lysosomal proteins transported in coated vesicles
- coated vesicle
- doesn’t change protein environment = highly favorable
coated vesicle
- encased by proteins acting as flexible scaffolding
—- buds of originating membrane
—- fuses to target membrane - preserves orientation of transmembrane protein
—-portions of the proteins in the vesicle that are in cytosol environment remain in cytosol
coated vesicle: parts
- clathrin
- COPI
- COPII
Clathrin
- forms flexible cages/protein called triskelions
—-transport mem and secretory proteins b/t golgi and plasma mem
—– participate in endocytosis (vacuole from mem for the purpose of taking in something)
COPI
- transports proteins b/t golgi compartment
- never leaves golgi
COPII
- transports proteins from Er to golgi
directing proteins
- carbohydrate recognition
- C-terminal sequences
carbohydrate recognition
- sugar code
- trafficking of lysosomal proteins depend on oligosaccharide
C-terminal sequences
- soluble resident ER proteins have C-terminal -Lys-Asp-Glu-Leu, -Lys-Lys-X-X, or -Lys-X-Lys-X-X-X where X = any AA
- if altered, secreted out of ER
vesicle fusion
- new membranes generated by expansion of existing membranes
—–vesicle buds off membrane and fuses to target membrane - biological membranes don’t spontaneously fuse, mediated by proteins called SNARE’s
R-SNAREs
- conserved Arg, associate w/ vesicle membranes
- single letter code
Q-SNAREs
- conserved Gln, associate w/ target membranes
- single letter code
- form coiled coils (a-b-c-d-e-f-g, a and b hydrophobic)
- see pseudo repeats = holds coil shape
membrane fusion
- zipping
- hemifusion
- two bilayers leflets farthest apart are brought together
- fusion pore formation
- fusion pore expands
virus fusion proteins
- mechanism & machinery diff from membrane fusion
- budding from infected cell - membrane enveloped virus
1. host cell recognition by virus
2. activation of viral membrane fusion machinery
3. fusion of viral membrane w host
(genetics) - integral proteins that recognize specific glycoproteins are gonna act as the cell surface receptors
- virus vesicles taken up by receptor mediated endocytosis (resembles of fusion of a vesicle w/in a mem)
