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69 Cards in this Set

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What is the cell membrane IMPERMEABLE to?
1. Hydrophilic ions
2. Molecules >4 Angst. radii
3. Molecules w/ C-chains 5+
So what items are incapable of passive transport across the membrane?
1. Glucose
2. Amino acids
3. Vitamins
4. Multi-valent anions/cations
What needs to take place in order for Impermeable items to be able to help keep the cell functional?
Maintainence of LARGE TRANSMEMBRANE CONCENTRATION DIFFERENCES.
What are the 4 important features of Membrane-bound Protein Carriers?
1. Intrinsic (integral) proteins
2. Multispan lipids in memb.
3. Cylindrical geometry
4. Central pore
How do membrane carriers NOT act?
AS FERRYBOATS - shuttling 1 molecule at a time; THAT WOULD BE ENERGETICALLY IMPOSSIBLE
How do membrane carriers transport items across the membrane?
By specifically binding item at intrinsic sites INSIDE the channel in sequential steps.
What are the kinetics of carrier-mediated membrane transport very similar to?
(2 concepts)
1. ENZYME-SUBSTRATE REACTIONS
2. Drug-Receptor interactions
At what substrate concentration is carrier-mediated transport -MORE RAPID?
-Slower?
-More rapid: LOW concentration
-Slow: high concentration
Why does low [substrate] allow transport to be faster?
B/c it allows transport to be even faster than predicted by Fick's law of simple diffusion!
Why is transport slower at higher concentration of substrate?
Because the # of carrier proteins becomes saturated and limits the rate of diffusion.
What is a very important feature of Carrier-mediated transport?
Specificity - eg RBCs only will allow d-glucose to be taken up, not l-glucose
What are 2 ways to regulate carrier transport proteins?
1. Regulate the Maximum Number of them in the membrane.
2. Regulate the number of binding sites available on them.
What is a good example of carrier-mediated transport?
Glucose - uptake in RBCs is specific for D isomer, not L.
What are 2 types of mechanisms that can inhibit transporters?
1. Competitive inhibition
2. Non-competitive inhibition
Define competitive inhibition
competition for the same site on the membrane transporter by 2 separate solutes
Give an example of competitive inhibition for the RBC
All different d-hexoses absorbed from the intestine compete for SLGT-1 for uptake.
What is Noncompetitive inhibition?
Stearic inhibition - when a substance attaches to the transporter at a site other than the carrier site
How does stearic inhibition hinder transport?
By reducing the carrier site's affinity for transported substrate.
What is Ouabain?
a cardiac glycoside that is a noncompetitive inhibitor of Na/K ATPase
What is the mechanism of Ouabain?
It binds an Extracellular site that prevents K+ from binding its carrier site.
What are the 3 types of Carrier-mediated transport?
1. Facilitated diffusion
2. Primary active transport
3. Secondary active transport
What is the definition of Facilitated diffusion?
Carrier-mediated transport of a non-charged molecule DOWN its chemical gradient; or an ION down an electrochemical gradient by means of a specific membrane-bound integral protein.
2 Important notes about facilitated diffusion:
-Faster than Fick's law predicts
-Exhibits a Tmax (Vmax)
What is the major function of facilitated diffusion?
To maintain a a rate of transport of essential molecules across membranes that is sufficient to sustain function.
What is the ENERGY source for facilitated transport?
Concentration gradient - chemical potential energy
What is NOT the energy source for facilitated transport?
Metabolic energy - ATP
What are 3 types of proteins that allow passive transport?
1. Pores
2. Channels
3. Carriers
What is the difference between pores and channels?
Pores are always open

Channels have gates
How are carriers different from pores and channels?
They allow facilitated diffusion, and have 2 lids that are never open at the same time.
What are the steps in facilitated diffusion?
#1
1. Outside-open carrier spontaneously binds solute to specific site in pore; causes outside gate to close.
What are the steps in facilitated diffusion?
#2
Inner gate opens and solute can move into cell
What are the steps in facilitated diffusion?
#3
Inner gate re-closes, then outer gate reopens.
Again, what is the energy source for this transport?
Chemical gradient - potential energy
What determines the direction of flux in facilitated diffusion?
Direction of chemical gradient
What will happen to net flux if the chemical gradient equalizes on both sides of membrane?
Flux will cease.
What is the classic example of facilitated diffusion?
Glut2 and Glut4 - on RBCs, liver , and fat cells.
What increases Glut2 in RBCs and myocytes?
Insulin - but not in liver cells.
What is Primary Active Transport?
ATP-driven transport of charged or uncharged molecules up their chemical or electrical gradients.
3 agents that inhibit primary active transport:
1. Cyanide
2. Dinitrophenol
3. Azide
Prime example of Primary active transport:
Na/K ATPase
What is the initial state of Na/K ATPase?
E1 - atp binds the alpha subunit and the pump is open to the intracellular space.
What binds Na/K ATPase when it is in the E1 state? Where on Na/K ATPase?
3 Na+ ions from inside the cell - to lumen sites on the alpha subunit.
What happens after Na binds the alpha subunit of Na/K ATPase?
ATP is hydrolyzed to ADP and the Pi phosphorylates the alpha subunit.
What is the result of phosphorylating the a-subunit of Na/K ATPase?
A conformation change to the E2-P state.
What does the E2P change cause?
Opening of the extracellular side of the channel - Na+ exits and E2P then switches to low-energy state.
What happens to Na/K ATPase in the Low-Energy E2P state?
2 K+ ions bind luminal sites in the membrane.
What happens to Na/K ATPase after K+ binds its lumen?
A conformation change back to the E1 state - hence K+ ions release
What is the stoichiometry of Na/K ATPase?
-3 Na+ out
-2 K+ in
Net of one Pos charge extruded
What term describes Na/K ATPase net pumping of one charge?
Electrogenic
What does electrogenic mean?
That Na/K ATPase contributes to the magnitude of the cell Em
What are the Cardiac Glycosides?
-Oubain
-Digoxin
-Digitalis
What is the mechanism of the cardiac glycosides?
Non-competitive inhibition - Binding of the empty E2P and changing its conformation to block K+ before it has the chance to bind.
Which cardiac glycosides are plant-derived steroids?
-Oubain
-Digoxin
Give another example of primary active transport that is NOT Na/K ATPase:
Ca2+ ATPases
What are two primary active transporters of calcium?
1. Ca2+ ATPase in the SR membrane of all myocytes
2. Ca2+ ATPase in the plasma membrane of all cells.
What is the function of the Ca2+ ATPase that is in the SR membrane of myocytes?
To sequester 2 Ca2+ ions (and 2 H+) from the myocyte cytoplasm into the SR per one ATP.
What is the function of the Ca2+ ATPase that is in all cell membranes?
To extrude one Ca2+ (and take up 1 H+) per ATP
What is one other example of an important primary active transport protein?
The H+/K+ pump
Where is the H+/K+ pump found?
In Parietal cells of
-Gastric glands
-Kidney tubule cells
-Intestinal cells
What is accomplished by the H+/K+ pump?
Puts 2 H+ into gland lumen and takes up 2 K+ per ATP molecule.
What is the functional importance of the H+/K+ pump?
Gastric digestion and K+ and Acid/base balance in the kidney.
So what are the three important types of Primary Active Transport?
Na/K ATPase
Ca ATPase (both types)
H+/K+ ATPase
What is the 3rd type of Carrier-mediated transport?
Secondary active transport
Define 2ndry active transport:
Same thing as primary but a different energy source.
What is the energy source for 2ndry active transport?
Chemical potential energy released when a couple molecule (Na) moved passively down its own electrochemical gradient.
So by definition what is secondary active transport?
Coupled transport - either:
-Co-transport (symport)
or
-Counter-transport (antiport)
Define Secondary Active Co-Transport:
Mvmt of 1 solute down its electrochem gradient coupled to mvmt of another solute AGAINST its own gradient, but both in the SAME DIRECTION.
What is an important 2ndry Active Counter-transport protein at the end of muscle contraction?
Na-Ca exchange
-3 Na+ go into cell
-1 Ca++ goes out
In general, what do counter-transport proteins exchange?
-Cations for cations

-Anions for anions