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37 Cards in this Set

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What is the purpose of biological membranes?
-boundaries of cells, organelles.
-define inside/outside of cells/organelles.
-confer cells/organelles "selective permeability"
What are the major components of biological membranes?
1) LIPIDS
-cholesterol--provide membrane fluidity
-sphingolipids-sphingomyelin (SP), gangliosides
-glycerol phospholipds--PC, PE, PG, PS, PI, CL
2) PROTEINS
-Integral-"INTEGRA"ted into lipid bilayer
-Peripheral-Not integrated, covalently attached.
3) CARBOHYDRATES
-Glycoprotein--attached to protein
-Glycolipid--attached to lipid
What is the generalized structure of biological membranes?
The lipids are ampipathic--with a hydrophobic tail and hydrophilic head. The lipids aggregate into a bilayer, with the hydrophilic heads exposed to the aqueous environment and the hydrophobic tails sandwiched in between. The lipid bilayers provide a selectively permeable fluid barrier to the outside environment.
How are lipids distributed in the membrane?
Lipids are distributed relatively evenly, with glycoproteins and glycolipids interspersed throughout. The membranes are fluid, so lipid molecules freely diffuse laterally.
What is a micelle?
-Microscopic (<20nm diameter), ball of lipids with hydrophilic head groups on the outside.
-Limited structures
What is a lipid bilayer?
-Bimolecular sheet
-Macroscopic (1mm diameter), with much movement of hydrophobic tails
What is a liposome?
-A micelle/lipid bilayer hybrid. A double layer of lipids surround a central aqueous chamber.
-Both the internal and external aqueous environments are exposed to the hydrophilic head groups.
Why are micelles and lipid bilayers important?
They shield hydrophobic regions from aqueous environment, while hydrophilic regions can contact aqueous environment.
Which arrangement--micelles or bilayer--is favored by biological lipids?
BILAYERS. The two fatty acyl chains are too bulky to fit into a micelle.
How do lipid bilayers form?
Self-assembly.
-The structure of a lipid bilayer is inherent in the structure of the individual lipid molecules (they are born to do it)
-The growth of lipid bilayers from phospholipids is rapid and spontaneous in aqueous solution.
How are lipid bilayers "cooperative structures"?
-They are held together by MANY non-covalent interactions, making them extensive.
-They close on themselves, so no edges are exposed to water, favoring "compartmentalization"
-They are "self-sealing"--a hole is energetically unfavorable.
What chemical forces stabilize lipid bilayers?
1) Hydrophobic interactions--"primary force". Occur between hydrophobic tails.
2) Van der Waals--Favor close packing of hydrophobic tails.
3) Electrostatic Interactions--Make hydrogen bonds between polar heads and water molecules in the solution.

(Look familiar? These are the same forces that stabilize proteins)
How can liposomes be used as vehicles for drug delivery?
Drugs/DNA put into liposome-->injected into patient-->liposome fuses with cell membrane-->delivers contents into cells (bypassing circulation and digestive system)-->can add targeting signals to make drug delivery more "selective"

*Really good for hydrophilic molecules--they can hang out in the aqueous center of the liposome.
If a membrane differs in function, what does that mean about its proteins?
Membranes that perform different functions contain different sets of proteins.
What are the two, main types of membrane proteins?
1) Integral
-Interact extensively with bilayer.
-Require detergent or organic solvent to solubize
2) Peripheral
-Loosely associated with membrane either: through interaction with integral proteins or polar head groups of lipids.
-Can also associate through covalently attached hydrophobic groups.
-Can be solubized by mild conditions, like: high ionic strength.
What are the different ways proteins can span the membrane?
1) Alpha helices
-Most common
-Composed of hydrophobic a.acids
-Cytoplasmic loops/extracellular loops composed of hydrophilic a.acids.
2) Beta Sheets
-Can form a channel protein
-Hydrophobic a.acids outside pore.
-Hydrophilic a.acids line aqueous central pore.
Do integral proteins have to span the lipid bilayer?
No. They do not need to span the membrane. Protein dimerization leads to the formation of a hydrophobic channel in the membrane.

Ex: Prostaglandin H2 Synthase-1
Why is the localization of Prostaglandin H2 Synthase-1 in the membrane important?
-Its substrate, arachidonic acid is hydrophobic. So, it does not need to leave the hydrophobic environment of the membrane to reach the active site of the enzyme.
Clinical correlation--how does aspirin inhibit prostaglandin synthesis?
Transfers an acetyl group to Ser 530 of hydrophobic channel, blocking substrate access to active site.
How do lipids move within membranes?
--Lipids rapidly diffuse laterally and don’t diffuse at all (practically) transversely.
--Lipids diffuse more rapidly at higher temperatures because fluidity is increased.
--High levels of cholesterol, short hydrophobic tails, and unsaturated tails increase fluidity also.
What determines the rate of diffusion of a molecule?
1) Diffusion coefficient (D)--describes lipid solubility of molecule.
Hydrophilic--slower diffusion
Hydrophobic--faster diffusion
2) Concentration gradient (Cside1/Cside2)--difference in concentration across membrane
-Always moves from low concentration-->high concentration.
-The greater the concentration gradient, the faster the rate of diffusion. (more molecules--faster diffusion)

*Multiply these values to determine overall diffusion rate:

***Rate-D x (Cside1/Cside2)
Which molecules use simple diffusion?
-Small, lipophilic molecules prefer simple diffusion.
-Sheds its solvation shell of water-->dissolves into hydrocarbon core of membrane-->diffuses through core to other side along conc. gradient-->resolvated by water.

*Large, polar molecules do not use simple diffusion--they are too big and moody!
What are membrane translocation systems?
-Membrane protein facilitates diffusion of molecule across membrane. Proteins can be saturated, so there is a transport maximum. Proteins are highly specific for charge/size and an be regulated by voltage or ligand gating.

Types:
1) Passive transport (aka: facilitated diffusion)
-No energy required
-High concentration-->low concentration
Ex: ACh receptor

2) Active Transport
-Needs energy
-Low concentration-->high concentration
Ex: Na+/K+ pump
Which molecules use membrane translocation systems?
Large, polar molecules!
What are two, good examples of membrane translocation systems?
1) Sodium-Potassium Pump (active):
-Uses ATP
-Exchanges Na/K against their conc. gradients.
-Establishes conc. gradients essential for synaptic transmission.

2) Acetylcholine receptor (passive):
-No ATP used.
-Exchanges Na/K along conc.gradients in response to neuronal signals.
-Example of ligand-gated ion channels.
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--sorry about that, ya'll! keep studying ;)
What is difference between primary and secondary active transport?
Primary--Uses ATP hydrolysis to transport ion against chemical gradient.

Secondary--Uses downhill flow of one gradient to power formation of another gradient.
What is difference between: uniport, symport, antiport?
uniport--one molecule diffuses at a time.

*symport--two molecules diffuse in same direction

*antiport--two molecules diffuse in opposite directions.

*examples of "cotransport"
Describe energetics of membrane translocation systems
1) Movement of UNCHARGED molecule from side 1-->side 2:

ΔG=RTxln (C side1/C side2)

2) Movement of CHARGED molecule (Z)

ΔG=RTxln(C side1/C side2) + ZFΔV

F=Faraday's Constant (23.1 kcal..)
ΔV=Potential (in volts) across membrane.
May be redundant, but..

What are key features and examples of membrane channels?
Features:
1) Passive transport
2) Faster translocation than transporters
3) May be gated.

Examples..

Voltage gated: Na+ channel
Ligand gated: AChR
cAMP regulated: Cl- channel
Other: Pressure sensitive
What are characteristics of transporters? What are some examples?
Transporter
-moves molecules slower than channels.

I) Passive
Uniporter
-K+channel-selectively transports K+. K+ions interact with carbonyl groups of the TVGYG sequence in selectivity filter. Na+ are too small to make interactions with channel.

2) Active

Primary/Uniporter
-Sarcoplasmic Reticulum Ca++ ATPase: transports CA++agains conc. gradient, using ATP.

Secondary/Symporter
-Na+-glucose Symporter--transports glucose against conc. gradient using downhill flow of Na+ along its conc. gradient.
What are characteristics of ionophores? Why can they be used for antibiotics?
-Ionophores are small molecules that surround ions and shuttle them across membranes.
-They allow free diffusion of ions across membranes which destabilizes membrane potential and can lead to the death of cells. They may be targeted for specific types of cells and thus act as antibiotics.
OVERALL--they transport ions and collapse gradient, which makes the cell mad.

Ex: Valinoycin-K+--small cyclic peptide that binds K+and carries it across the membrane.
Redundant, but..WHAT is the summary of all membrane transport types?
1) Simple diffusion
--High conc-->low conc.
--No ATP
--No transport system
--Non-polar compounds only.

2) Facilitated diffusion
--High conc-->low conc.
--No ATP

3) Active (transport systems)
--Low conc-->High conc.
--ATP needed.
Primary
--Uses ATP directly
Secondary
--Coupled to positive chem. gradient.

4) Ion channels
-High conc-->low conc.
-Can be gated or not.

5) Ionophores
-Used in medications; etc.
-Moves ion, destroys conc. gradient, destroys cell.
this card was made accidentally
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What are the TWO types of transport that exist using membrane translocation systems?
Passive (aka:facilitated)
--ACh receptor

Active
--Na+/K+ pump
How do membrane translocation systems differ?
--In NUMBER and DIRECTIONALITY of the solutes.

--Can be uniport, symport, or antiport.

--Classification is INDEPENDENT of whether transport is active or passive.
What is MAIN difference between membrane CHANNELS vs. membrane TRANSPORTERS?
--They are both types of membrane translocation systems.

--They have different rates of translocation (channels are faster than transporters)

CHANNELS
--ONLY passive transport
Ex:
Voltage gated-->Na+ channel, K+ channel
Ligand gated-->ACh Receptor
cAMP regulated-->Cl- channel
Other-->pressure sensitive

TRANSPORTER-->BOTH passive and active transport

Ex:
Passive-->glucose transporter

Primary Active
--> Na+/K+ pump (ATPase)
--> Respiratory chain linked (redox-coupled)
-->Multidrug resistance protein transporter (ATP Binding cassette)

Secondary Active
-->Na+ dependent glucose transport