Lecture 9 - Exam Flashcards
What is the purpose of proteins embedded in membranes?
Water channels, ion channels, receptors and cell attachment
What are the different types of membrane proteins?
Transmembrane, integral, and peripheral
What are the components of the transmembrane proteins?
Extracellular domain, transmembrane spanning domain, and intracellular/cytosolic domain
What are integral membrane proteins?
Embedded in membrane, but do not span it
What are peripheral membrane proteins?
Proteins on either the intra- or extracellular domains that can interact with the other proteins
What is an additional function of anchoring proteins that interact with membrane proteins?
Cell signaling
What are caveolae? And what do they play an important role in?
Flask shaped invaginations on the cell surface - type of membrane raft - regulate expression of receptors and transporters by controlling how many are present on the surface of cells
What is the order of membrane rafts?
Ordered phase that float in sea of poorly ordered lipids
What can membrane fluidity affect?
Function and organization of rafts - spatially organize signaling molecules to promote kinetically favorable interactions necessary for signal transduction - can also conversely separate signaling molecules inhibiting interactions and dampening signaling responses
What is the membrane permeable to? and what kind of transport do these molecules use?
Gases and small uncharged polar molecules - passive diffusion
What is the membrane impermeable to?
Large, uncharged polar molecules, ions, charged polar molecules (hydrophilic) - need transporters
What is the partition coefficient?
K, ratio of solute concentration in oil: solute concentration in water - K>1 is more lipid soluble and K<1 is more water soluble
What is LIpinskin’s Rule of Five?
In the absence of a transporter, diffusion across a membrane can not have more than 5 hydrogen bond donors (N or O with one or more hydrogen atoms), not more than 10 hydrogen bond acceptors (N or O), molecular mass no greater than 500 daltons, and an octanol-water partition coefficient log P not greater than 5 - must be transported if it doesn’t meet these rules
What are active transporters?
ATPases that require energy to move things against a gradient
What are secondary active transporters? And what is another name for it?
Facilitated diffusion - Require another molecule to work and the other molecule is driven by an active transporter
What are proteins that move phospholipids from one side of a bilayer to the other called? Does it require energy?
Flippases, can require energy or be passive - but reduces half time for the movement significantly
What are the classes of ATPase active transport pumps?
P-class, F- and V- class, ABC superfamily
What are P-class pumps? and where are they found?
A type of active transporter - proton pumps - H+K+ pump in the stomach gives acidic environment when parietal cells produce HCl and pumps H in, H+ pump on PM of plants, fungi, bacteria and as Na+K+ pump on PM of euk, Ca2+ pump in PM of all euk cells and sarcoplasmic reticulum
What drug inhibits P class pumps?
Esomeprazole - Nexium brand name for stomach (HK), oubain and digoxin (NaK)
What is the ABC superfamily of active transporters? and where are they found? What is an example?
Large family of pumps that move hydrophobic substrances - prevent xenobiotics from entering - normally move cholesterol and phospholipids out, inducible expression - found on bacterial and mammalian PM - p-glycoprotein is an example and is part of the multi-drug resistance family - MDR1
What is the V class of active transporters? and where are they found?
Only pump Hydrogen ions - found on vacuolar membranes, endosomal and lysosmal membranes, and PMs of osteoclasts and kidney tubules
How does the sodium-potassium pump work?
It brings two potassium ions in and three sodium ions out by undergoing phosphorylation conformational change to create an electrical potential that can be used to do work to move co-transporters
What causes muscle contraction? And what blocks the channel?
Depolarization of the sarcoplasmic reticulum activates the ryanodine channel to release Ca++ causing contraction - blocked by dantrolene - caffeine can reduce the threshold for calcium release
What is an important function of a v-class proton pump? And what can this activity lead to?
Maintains acidity inside of organelles (keeps pH inside lysosomes at 4.5 ) - trigger function to create a gradient that can drive co-transport (VMAT - vesicular monoamine transporter)
What is Marble bone disease and Albers-Schonberg and what causes is?
AKA Osteopetrosis - genetic disorder in which bones harden and become denser and is a result of a V-pump mutation or channelopathy
What is ion trapping?
V-class pumps are able to trap NTs inside of their vesicle through use of the VMAT
What inhibits VMAT and where are VMATs found?
VMAT2 found on synaptic vesicles inhibited by reserpine and tetrabenazine
VMAT1 found in adrenal medulla
What does ABC superfamily stand for?
ATPase Binding Cassette
Which pumps cause issues with cancer treatment and those involved in the BBB and GI brush border?
ABC superfamily - give multi drug resistance
What drugs did MDR-1 become resistant to?
Vincristine - Oncovin brand name - aka leurocristine - a mitotic inhibitor used in cancer chemotherapy
What inhibits p-glycoprotein?
Favinoids naringin and naringenin
What are some characteristics of transport proteins?
Faster than passive diffusion,partition coefficient K is irrelevant, it is saturable, it is specific and it is subject to inhibition by competition at binding site
What is a uniporter and what is a common example?
Transfer one molecule down a concentration gradient, glucose transporters
What are symporters and antiporters?
Secondary active transporters that move substances against concentration gradients by taking advantage of a molecule that is moving down its gradient - sodium dependent glucose transporters - VMAT can act as an antiporter
What is Donnan Equilibrium?
Cell contains more negative proteins and so ion distribution distributes accordingly
How can ion channels be gated?
Ligand, voltage, pH, oxygen tension
What can enhance or inhibit the effects on ligand gated ion channels?
Multiple regulator sites - not the same for everyone
What can facilitate the transport of water through membranes and what is it regulated by?
Aquaporins - prevent ions from crossing - regulated by ADH production form pituitary
What is tonicity?
Amount of solute in the extracellular space
What is hypotonic and hypertonic?
Hypotonic - less solute outside than inside
Hypertonic - more solute outside than in
Moves from low to high
What is oncotic pressure?
AKA colloid osmotic pressure - A form of osmotic pressure exerted by proteins (albumin) in a blood vessel’s plasma that tends to pull water into the circulatory system
Do transport proteins exist by themselves?
No - they must be coupled with other transporters to ensure pH, osmotic, oncotic, concentration and electrochemical gradients
How do cell’s maintain pH gradient?
Different antiporters that neutralize to maintain proper pH
Na/H antiporter becomes more active to pump more H ions out if pH becomes too acidic
Bicarb/Cl antiporter does as well
How does the NaK pump create action potential? And what is the rate of change dependent on?
Sodium channels open and sodium enters cell –> Potassium channels open and potassium begins to leave cell (raising potential) –> Sodium channels close –> Rest of potassium leaves cell (lowering potential and creating overshot) –> Potassium channels close and excess potassium diffuses away - dependent upon density of channels
What are graded potentials?
Depolarizations that do not reach adequate voltage change or threshold potential to activate voltage gater chanels
