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31 Cards in this Set

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  • Back
What molecules can freely diffuse across the membrane?
1. Small hydrophobic molecules (O2, CO2, N2, benzene)
2. Small uncharged polar molecules (H2O, glycerol, ethanol)
What molecules cannot freely diffuse across the membrane?
1. Larger uncharged polar molecules (amino acids, glucose, nucleotides)
2. Ions (ie: H+, Na+, HCO3-, K+, Ca2+, Cl-, Mg2+)
What is the Solubility-Diffusion model of permeability?
A solute diffuses from water into the lipid bilayer -> solute diffuses across the lipid bilayer -> solute diffuses in water on far side of the membrane.
* There is equilibrium between water and the solute on both sides of the bilayer.
What is the partition coefficient equation?
P = [Drug]organic/[Drug]aqueous
What is the partition coefficient?
The ratio of concentrations on two sides of a bilayer.
What is the relationship between partition coefficients of two drugs?
They typically have similar P values.
If a compound is very water-soluble how well can it cross the bilayer?
Not well, it cannot cross the hydrophobic portion of the bilayer.
If a compound is very organic-soluble how well can it cross the bilayer?
Too well, it has a hard time leaving the hydrophobic membrane.
How do protein metabolites cross the membrane?
Via transport proteins
How do drug molecules cross membranes?
Via diffusion
What is the Henderson-Hasselbalch equation?
pH = pKa + log [A-]/[HA]
When does the pH = pKa?
When equal concentrations of the acid and conjugate base are present
What form is an acid in, at an acidic pH?
The acid is in the neutral, unionized, form.

*because the solution is rich in protons the acid doesn't need to give one up.
What form is an acid in, at a basic pH?
The acid is ionized, deprotonated, at basic pH
When are bases neutral? ionized?
Bases are generally neutral at higher pH and become more ionized at lower pH.
What happens to the percent ionized each time the pK and pH increases by one unit?
The percent ionized increases 10 times each time the difference between the pK and pH increases by one unit.
If an acid has a pKa of 3.5, what percent of the acid are neutral in blood (pH=7.4)? stomach (pH = 2.5)?
1. <0.1%
2. 91%
If an acid has a pKa of 3.5, what percent of the acid are ionized in blood (pH=7.4)? stomach (pH = 2.5)?
1. 99.9%
2. 9%
If a base has a pKa of 9.5, what percent of the base are neutral in blood (pH=7.4)?
.99%
If a molecule has a pKa of 8.5, what percent of the molecules are ionized in blood (pH=7.4)?
91%
If an acid has a pKa of 7.4, what percent of the acid are neutral in blood (pH=7.4)? ionized?
1. 50%
2. 50%
What is the pore model of permeability?
Hydrated pores through the lipid bilayer are transiently formed because of thermal fluctuations.
What is the importance of the pore model of permeability for diffusion?
The pore model of permeability allows molecules to bypass the high thermodynamic barrier that dissolving in the lipid bilayer requires.
What affect does membrane thickness have on permeability of small polar molecules?
Thickness relates to distance required to diffuse, so the greater the thickness, the greater the distance the molecule must diffuse, which means less likely the molecule will diffuse across the membrane.
What diffusion model is dependent on membrane thickness?
Pore model of permeability
How do protons diffuse across a membrane?
A "water wire" carries the protons across the membrane.
What essential feature of aquaporins prevents protons to transport across the membrane?
Aquaporin proteins break up the water-wire and prevent the proton from being transported through the membrane.
How do you calculate osmolarity?
pi = nCRT

pi = osmolarity
n = number of dissociable particles per molecule
C = solute concentration
R = gas constant
T = temperature in Kelvin
What is the transition temperature?
The set-point at which below this temperature lipids behave more like solids, above this temperature lipids behave more like liquids.
How does cholesterol affect the transition temperature?
*Cholesterol lowers the transition temperature, allowing lipids to behave more like a fluid at lower temperatures.
*Prevents a drastic change in transition between solid and liquid lipid states.
What is the solubility of glycerol in the bilayer dependent on?
1. Cholesterol composition of bilayer
2. Ratio of saturated to unsaturated lipids.