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Biochemistry - MOD2 - Structure of Membranes and Transport
pgs 1 - 16
40
Chemistry
Professional
09/15/2010

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Term
lipids in membranes (6 types of glyceryl phospholipids)
Definition
cholesterol

sphingolipids (sphingomyelin (SP) and gangliosides)

glyceryl phospholipids:
phosphatidylcholine (PC)
phosphatidlyethanolamine (PE)
phosphatidylglycerol (PG)
phosphatidlyserine (PS)
phosphatidlyinositol (PI)
cardiolipin (CL)
Term
carbohydrates in membranes
Definition
in the form of GLYCOPROTEIN and GLYCOLIPID

NEVER FREE
Term
micelles
Definition
ball arrangement of amphipathic molecules
Term
which amphipathic arrangement is favored?
Definition
BILAYERS

two fatty acid chains of a phospholipid or glycolipid are too bulky for micelle
Term
how are lipid bilayers cooperative structures (3 things)?
Definition
they are held together by NON-COVALENT interactions (makes them extensive)

they close on themselves; no hydrocarbons exposed; favors COMPARTMENTALIZATION

they are SELF-SEALING; hole energetically unfavorable
Term
what forces stabilize lipid bilayers? which is the primary?
Definition
Hydrophobic interactions (primary)

van der waals - happens between hydrocarbon tails; favors close packing

electrostatic interactions - polar head to water molecules
Term
do the same chemical forces that stabilize protein structures stabilize lipid bilayers?
Definition
YES, same thing
Term
how can we form liposomes?
Definition
sonicate suitable phospholipids (high freq sound waves)

form 50nm lipid vesicles called liposomes
Term
liposomes are used for...
Definition
water soluble drugs can be put inside and carried into cell

drugs or DNA for gene-therapy may be incorporated into a liposome

they BIPASS BOTH THE CIRCULATION and DIGESTIVE SYSTEM - go directly into cell
Term
how can you solubilize integral proteins?
Definition
detergent or organic solvent
Term
how can you solubilize peripheral membrane proteins?
Definition
mild conditions - high ionic strength
Term
what is the most common structural motif for crossing the membrane in integral proteins?
Definition
alpha helices

composed of hydrophobic amino acids

cytoplasmic loops and extracellular loops are composed of hydrophilic aa's
Term
what structural motif are channel proteins made mostly of?
Definition
beta sheets (barrel form)p
Term
do integral membrane proteins necessarily span the entire lipid bilayer?
Definition
NO

prostaglandin H2 synthetase-1
Term
prostaglandin H2 synthetase-1
Definition
its dimerization leads to formation of hydrophobic channel

its substrate is arachidonic acid (hydrophobic)

this protein/enzyme needs to be half inside the membrane because arachidonic acid is generated from hydrolysis of membrane lipids - it is important that the substrate doesn't leave this hydrophobic environment before getting to the enzyme

synthesis inhibited by ASPIRIN
Term
aspirin inhibits what and how?
Definition
inhibits prostaglandin synthesis by transferring an acetyl group to ser530 of this channel, which blocks substrate (arachidonic acid) access to active site
Term
in what ways can peripheral membrane proteins covalently attach to hydrophobic groups
Definition
cysteine can attach straight to fatty acids

c-terminus can attach to hydrophobic head (such as glycosyl phosphatidyl inositol (GPI) anchor)
Term
Tm
Definition
melting temperature

temp at which half of the lipid molecules are solid and half are fluid
Term
what controls membrane fluidity?
Definition
controlled by fatty acid composition and cholesterol content

# of carbons if have same number of double bonds (higher the #, higher the Tm;low # = more fluid)

presence and # of double bonds greatly decreases Tm
Term
diffusion coefficient (D)
Definition
function of the lipid solubility of the molecule

hydrophilic molecules diffuse more slowly while hydrophobic molecules (steriods fatty acids) diffuse more rapidly
Term
concentration gradient
Definition
Cside1/Cside2

difference in concentration across the membrane

diffusion occurs from a region of higher concentration to a region of lower concentration

for any given molecule, the greater the concentration gradient the greater the rate of diffusion
Term
overall rate of diffusion
Definition
determined by multiplying the diffusion coefficient and the magnitude of the concentration gradient

rate = D x (Cside1/Cside2)
Term
how do we get large polar molecules across the membrane
Definition
can't simple diffusion

use membrane translocation systems (proteins)
passive transport
active transport
Term
passive transport
Definition
facilitated diffusion

same direction as concentration gradient - thus, does not require input of energy

ex - acetylcholine receptor: passively transports sodium and potassium ions along their concentration gradients in response to neuronal signals (ligand-gated ion channel)
Term
active transport
Definition
transport goes in opposite direction of concentration gradient - thus, requires energy

ex - sodium-potassium pump: actively exchanges sodium and potassium against their concentration gradients utilizing the energy of ATP hydrolysis

establishes the concentration gradients of sodium and potassium essential for resting membrane potential and thus synaptic transmission
Term
types of channels (passive transport)
Definition
voltage gated

ligand gated

cAMP regulated

other (pressure sensitive)
Term
types of transporters (passive and active transport)
Definition
glucose transporter (passive)

1*-ATPase (Na/K pump)

1*-redox coupled (respiratory chain linked)

ATP-binding cassette (multidrug resistance protein transporter)

2* (Na-dependent glucose transport)
Term
primary active transport
Definition
ATP hydrolysis used to transport a molecule AGAINST its concentration gradient

ex - Na/K pump
Term
secondary active transport
Definition
gradient of molecule X first established using primary active transport

movement of molecule X back down its concentration gradient then provides energy to drive COTRANSPORT of second solute S against its concentration gradient
Term
types of cotransporters
Definition
symport (two molecules in the same direction)

antiport (different directions)
Term
prostaglandin H2 synthase-1
Definition
half within lipid bilayer

important that this enzyme is within the membrane so that its substrate, ARACHIDONIC ACID, which is a hydrophobic molecule generated by the hydrolysis of membrane lipids, doesn't have to leave the hydrophobic environment of the membrane to reach the active site of the enzyme.

CC - Aspirin blocks prostaglandin synthesis by transferring an acetyl group to ser530 of the channel - blocks substrate access to active site
Term
what does aspirin do?
Definition
it inhibits prostaglandin H2 synthase-1

blocks active site from arachidonic acid by acetylating Ser530 inside the hydrophobic channel
Term
Tm (melting temperature)
Definition
temperature at which half of the lipid molecules are solid and half are fluid
Term
sarcoplasmic reticulum Ca++ ATPase
Definition
moves 2 calcium per ATP
Term
what are the 6 steps of calcium movement in the sarcoplasmic Ca++ ATPase
Definition
1. Binding (ATP + 2Ca++ --> SRC ATPase)
2. Phosphorylation
3. Eversion (conformational change)
4. Release (of Ca++ to other side)
5. Hydrolysis (of Pi group on protein)
6. Eversion (change back to original conformation)
Term
what are the side chains that allow K+ to be selected to go down a K+ voltage gated channel
Definition
TVGYG

Threonine
Valine
Glycine
Tyrosine
Glycine
Term
briefly describe the opening/closing steps involved in K+ ion channel
Definition
membrane depolarizes, causing channel change conformation (more + charges move towards ECM while more - charges move closer to cytosol end)

negative charges now on the cytosolic side attract the positively charged ball (INACTIVATION GATE)

ball then binds to and closes the channel - inactivation
Term
what are ionophores

give an example of an ionophore

what does it do?
Definition
Valinomycin

ionophores are small molecules that surround ions and shuttle them across membranes, disrupting ion gradients = VERY HARMFUL

ionophores specific for certain microorganisms are potent antibiotics

VALINOMYCIN disrupts K+ gradients; MONENSIN disrupts Na+ gradients
Term
VALINOMYCIN
Definition
disrupts K+ gradients
Term
MONENSIN
Definition
disrupts Na+ gradient
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