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97 Cards in this Set

  • Front
  • Back
what properties make up a biological cell membrane?
closed boundaries (sheet-like structures)

composed of lipids and proteins with varying ranges

lipids have both hydro-phobic and philic moieties

proteins serve many functions (pumps, channels, receptors, enzymes)

everything is held together noncovalently

two sides are assymetrical and 2-D fluid structures

polarized (inside -60mV)
how thick is a typical membrane?
60 A to 100 A
(6 nm to 10 nm)
what is a fatty acid?
gives membrane hydrophobic quality

long hydrocarbon chains with varying lengths and degrees of unsaturation with a COO- on the end.
C18:0

C18:1

C18:2

C18:3

name these bad boys
C18:0 octadecanOIC ACID

C18:1 octadecENOIC ACID

C18:2 octadecaDIENOIC ACID

C18:3 octadecaTRIENOIC ACID
Where does the numbering start on a fatty acid?
at carboxy terminus

C2 is a
C3 is B
terminal methyl is Omega
what does cis^9 tell you naming wise?

Why is Omega 3 fatty acid confusing from a naming and counting standpoint?
there is a double bond that is cis between 9 and 10

Omega 3 is confusing because you are counting starting from the Omega (distal) end of the thing and the double bond is then starting at 3 to 4.
At pH 7, what form are fatty acids found in?
ionized form

palmitate (not palmitic acid)

oleate (not oleic acid)

refer to them as their carboxylate forms
C14:0
Myristate
n-Tetradecanoate
CH3(CH2)12COO-
C16:0
Palmitate
n-Hexadecanoate
CH3(CH2)14COO-
C18:0
Stearate
n-Octadecanoate
CH3(CH2)16COO-
C20:0
Arachadecaonate
n-Eicosanoate
CH3(CH2)18COO-
C16:1
Palmitoleate
cis-^9-Hexadecenoate
CH3(CH2)5CH==CH(CH2)7COO-
C18:1
Oleate
cis-^9-Octadecenoate
CH3(CH2)7CH==CH(CH2)7COO-
C18:2
Linoleate
cis, cis-^9, ^12- Octadecadienoate
CH3(CH2)4(CH==CHCH2)2(CH)6COO-
C18:3
Linoleate
all cis -^9, ^12, ^15-Octadecatrienoate
CH3CH2(CH==CHCH2)3(CH2)6COO-
C20:4
Arachidonate
all cis-^5, ^8, ^11, ^14-Eicosatetraenoate
CH3(CH2)4(CH==CHCH2)4(CH2)2COO-
What is the typical biological range of Carbons on a fatty acid?
14-24 (usually even #)

16-18 most common
What impact does higher degrees of unsaturation have on a fatty acid?
lowers the melting point

becomes more fluid
what are phospholipids?
water insoluable, but soluable in organic solvents.

serve as hydrophobic and hydrophilic interacter for messaging, transducting and fuel
describe a phospholipid
1 or more fatty acid

platform for fatty acid attachment (glycerol or sphingosine)

phosphate

alcohol on the phosphate
What is this?
phospholipid
Describe phosphatidate
simplest phosphoglyceride

3-Carbon glycerol platform with C-1 and C-2 esterified to fatty acid carboxyl groups
C-3 is esterified to a phosphate group
What are the 2 fatty acids on a phosphoglyceride typically?
C1 is stearate (C18:0)

C2 is arachidonate (C20:0)
what are the major phosphoglycerides?
derived from phosphatidate

add either
Ser
ethanolamine
choline
glycerol
inositol

with an ester bond to the phosphate and hydroxl of alchohol
name these bad boys and memorize their functional groups
Ser

ethanolamine

choline (3 methyls on the amine)

glycerol

inositol
name these phosphoglycerides
Phosphatidylserine (PS)

Phosphatidylcholine (PC)

Phosphatidylethanolamine (PE)

Phosphatidylinositol (PI)
Name these structures
sphingosine

sphingomyelin
where is the fatty acid attached to in sphingomyelin?
the amine of C2
what is a glycolipid?
sugar-containing lipids. Like sphingomyelin it is platformed of off sphingosine.

It is different from sphingomyelin by having a sugar attached to the primary hydroxyl of sphingosine
How is this lipid different from sphingomyelin?
cerebroside

glycolipid
What are gangliosides?

Where are the sugars located with regard to the cell?
more complex glycolipids

branched chain of up to 7 sugar residues

sugars of glycolipids are always extracellular
Describe cholesterol.
steroid with 4 linked hydrocarbon rings.
on one end is a hydrocarbon tail and a hydroxyl group on the other end.
What is the orientation of cholesterol in the cell membrane?
parallel to phospholipids because the hydroxyl tail interacts with the proximal phospholipid head
cholesterol is found in all membranes of every kind of life form. verdad o falso?
False. Prokaryotes do not have cholesterol.
How are archea membranes unique?
non-polar chains attached to glycerol backbone

glycerol stereochemistry is inverted compared to phosphatidate

alkyl chains are branched and saturated

due to ether linkage they are resistant to hydrolysis and due to alkyl chains resistant to oxidation

lipids help archea withstand high temps, high salt, low PH
what is this structure and why is it unique?
archea lipid

branched, saturated alkyl chains with ether linkage

inverted stereochem of glycerol
what is an amphipathic molecule?
molecule with both hydrophilic and hydrophobic moieties

circle likes water, green tails hate water
what is a micelle?
small globular structure <200A (20nm) in diameter
what is a lipid bilayer?
2 sheets of lipids.

Tails interact with eachother while the heads face out and interact with water.

middle part is now a permeable barrier

can form more extensive dimensions (1mm) over the micelle config. (those fatty acids won't fit in the middle)
Give an example of a molecule that readily forms a micelle?
sodium palmitate
(only has one single fatty acid chain)
describe the forces that make for lipid bilayers forming rapidly and spontaneously.
hydrophobic tail forces and van der waals forces between the hydrocarbon tails

hydrophilic forces of water interacting with heads
(electrostatic and H bonding)
what does cooperative structure mean?
many reinforcing, noncovalent interactions

makes lipid bilayers extensive, compartmentalized and self-sealing
what is a liposome?
the creation of a lipid vessicle with an aqueous center

important because it allows us to study membrane permeability and to deliver drugs in the aqueous bit
how do you form a liposome?
put PC in aq medium and sonicate

vessicles are uniform, spherical and about (50nm) in diameter
describe molecular trapping.
first you make the liposomes with GLY in the vessicle.

Then you can observe how the GLY gets out and determine the lipid bilayers permeability to GLY

You can also insert proteins using a detergent to see how permeability is effected
what is doxil?
long-acting liposomal version of doxorubicin used to treat a variety of cancers

greater efficacy and lower cardiotoxicity
What is Lipoplatin?
liposomal cisplatin 110 nm

treat karposi's sarcoma and multiple myeloma

reduced nephrotoxicity, peripheral neuropathy, ototoxicity, myelotoxicity, and less nausea and vomiting
How is the permeability of a lipid bilayer different for water and Na or K?
lipid bilayers are relatively impermeable to ions and polar molecules

But water, with its small size, abundance and lack of charge goes through easily
describe how a small molecule might make "break on through, to the other side"
solvates in water, dissolves in hydrocarbon core of membrane, diffuses on through and gets re-solvated on the other side.

So those that easily replace their coordination shell are more quickly permeable
Are ions more or less permeable than glucose?

Is Glucose more or less permeable than indole?
ions less permeable than glucose

glucose less permeable than indole?
Why is Tryptophan less permeable than indole?
indole lacks ionic groups--more energetically favorable to pass through the hydrophilic center of membrane
describe the relationship between membrane lipids and proteins
protiens transport chemicals and info across a membrane

membrane lipids create the appropriate environment for the action of these proteins
what is the concentration of proteins for an electrically insulated environment like a nerve cell membrane?
18% proteins in myelin and those proteins will be found in the synapses
what is the concentration of proteins in a metabollically active membrane?
50% proteins in plasma membranes
pumps channels receptors and enzymes
What concentration of proteins make up an energy transducing membrane?
inner mitochondrial membrane is a whopping 75% proteins.
Not as much lipids but a lot of cardiolipin
what are the 3 ways proteins can be associated with membranes?
peripherally
integrally
half and half (bottom half of protein has series of a helices that interact with hydrophobic middle of membrane)
how are peripheral membrane proteins attached to membrane?
electrostatic and H bonded to lipid heads

bind to integral proteins

hydrophobic fatty acid chain attaches to lipid bilayer
How are integral proteins anchored in membrane?
They interact extensively with the hydrocarbon middle tails
What are 2 types of structures for integral membrane proteins?
a helices

B strands
describe bacteriorhodopsin
7 perpendicular a helices span 45 A width of cell membrane

H+ gradient uses light energy to pump H+ out and synthesize ATP

a helics are hydrophobic with non polar residues sticking out
what are the most common structural motif in membrane spanning proteins?
a-helices
what is a porin?
channel protein

single antiparallel B-sheet which folds in a way to make a cylindrical channel

The outside surface is nonpolar

The inside surface is hydrophilic and water filled
Where are porins commonly found?
E. coli
How is the compatible structure of a porin created?
alternating hydrophobic and hydrophilic residues that are h-bonded diagonally.
draw the structure for arachidonate
what is prostaglandin H2 synthase-1 and what does it do?
an enzyme that catalyzes the conversion of arachidonic acid into prostaglandin H2

Initiates COX-1 (cyclooxygenase rxn)
(perioxidase rxn)
what does prostaglandin H2 do in the body?
promotes inflammation and modulates gastric acid secretion
how does prostaglandin H2 differ synthase-1 differ from bacteriorhodopsin?
it has a-helices, but they are on the bottom of the protein and their hydrophobic amino acid side chains are what is imbedded in the membrane
What is thromboxane A2?
prothrombolitic
activation and aggregation of platelets

causes vasoconstriction

BAD

aspirin works for keeping blood thinner by irreversibly inhibiting COX-1 and thus the formation of Prostaglandin H2 and thus TXA2
What is PGI2 (prostacyclin)
eicosanoid

decreases platelet aggregation

causes vasodilation

GOOD
Is prostaglandin H2 synthase 1 an integral or peripheral protein?
integral, even though it is not fully imbedded.

Requires organic solvent or detergent to isolate that sucker.
which residue inside the COX-1 protein channel gets the inhibiting aspirin acetyl group?
Ser 530
What are 2 important feature of how proteins interact with membranes?
1). parts of protein that interact with hydrophobic part of membrane are coated with non-polar amino acids side chains and parts interacting with aq part are hydrophilic

2). imbedded structures are quite regular participate in H bonding which are difficult to sever
name the anchors for

palmitoyl

farnesyl

GPI
thioester

C-terminus

C-terminus
name the 10 non polar amino acid residues
P-lease
M-ail
I-n
L-ove
C-ards
Tr-pping
A
Th-reesome
Girly Gly
What is the "window" in hydropathy plot?
sequence of 20 residues in which the calculations of free energy will determine whether they are imbedded o or not.

The calculations are plotted against the first amino acid at the start of the window and anything over +20 kcal/mol indicates a likely membrane spanning window.
what is glycophorin?
an erythrocyte membrane protein that has a predicted membrane spanning region from a hydropathy plot which has been proven experimentally.
Are hydrophathy plots always correct?
No, even some soluable proteins contain large non-polar regions and some membrane spanning protein segments go undetected by hydropathy plots, like porin.
Describe the FRAP process of determining lateral diffusion
--cell surface fluoresces with labled surface

--fluorescent area is bleached and destroyed

--fluorescence intensity recovers as diffusion occurs.

--the rate of recover depends on the diffusion coefficient
what is the diffusion coefficient of phospholipids?
1 Mm2s-1

diffuses ~2Mm / s

(this ~100x that of water--more like olive oil)
what is the diffusion coefficient of proteins?

what is a fast protein?

What is a slow protein?
a range

fast protein is photoreceptor protein rhodopsin
0.4 Mm2/s

slow protein is peripheral glycoprotein fibronectin
<10-4 Mm2/s
Why is fibronectin a slow diffuser?
anchored to actin filaments through transmembrane protein integrin (stuck in the extracellular matrix and cytoskeleton)
what is the fluid mosaic model?
membranes are 2-D solutions of oriented lipids and globular proteins

lipid bilayer is a solvent for integral proteins and a permeability barrier

membrane proteins are free to diffuse laterally in lipid matrix.
what is transverse diffusion
flip flop.

takes a long time 10 to 9th as long as a lipid laterally diffuses 50 A.
Where are PE and PS predominantly located?
The aminophospholipids, phosphatidylethanolamine (PE) and in particular phosphatidylserine (PS) are preferentially located in the inner leaflet of the membrane bilayer
Where are sphingomyelin and PC predominantly located?
the other major components sphingomyelin (SM) and phosphatidylcholine (PC) are more abundant in the outer leaflet
what are flippases?
translocater which flip flops PE and PS from outer to inner
What are floppases?
move phospholipids from inner to outer

needs ATP
ABC transporter family
What are scramblases?
move any phospholipid across bilayer down its concentration gradient

does not need ATP
What is membrane fluidity depend upon?
The composition of fatty acids and their properties.

rigid fatty acids are saturated and unbent with lots of good H bonding and thus higher melting points

more fluid membranes have unsaturated fatty acids that are bent and thus less H bonds and thus lower melting points.
How does fatty acid chain length influence fluidity of membranes?
each additional -CH2- adds -0.5 kcal/mol to free energy of interaction between 2 adjacent hydrocarbon chains.

longer chains interact more strongly
How does E. coli alter its fatty acid chains when it is trying to grow in colder temps?
decreases the ratio of saturated to unsaturated so that there are less rigid (saturated) fatty acids which prevents the membrane from becoming too rigid in this colder environment
How do animals regulate membrane fluidity?
cholesterol
what structurally about cholesterol helps it regulate membrane fluidity?
bulky steroid nuclues with a hydroxl group at one end and a flexible hydrocarbon tail at the other.

hydroxyl group interacts with aqueous environment (head group)

hydrocarbon tail is in non-polar core
what is a lipid raft?
cholesterol forms complexes with certain phospholipids concentrated in certain areas of the membrane.

These guys serve to moderate membrane fluidity. Makes them less fluid but also less likely to experience phase change
asymmetric membranes means what?
inside and outside have different components and enzymes and thus different activities.

Na+ and K+ ATPase pump

Na+ and ATP inside cell

K+ outside
what is ouabain?
cardiotonic steroid that inhibits the Na+ and K+ pumps

ONLY works on outside of cell.