BICD 110 Lecture Notes - Lecture 3: Chloroquine, P-Glycoprotein, Potassium Channel
28 Jun 2018
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BICD110 Lecture 3 Notes 4/10/18
- Due to hydrophobic interior, lipid bilayer surrounding cells and organelles acts as a highly
impermeable barrier to most water-soluble (polar) molecules
oMechanisms evolved mediated by special transmembrane proteins to take up nutrients,
secrete waste, and transport molecules
- Simple diffusion: given enough time, any molecule will cross membrane
oRate at which this occurs depends on size and solubility in hydrophobic environment
oFrom fast to slow:
Oxygen, nitrogen, and carbon dioxide can cross
109 faster than charged ions
Large hydrophobic molecules (benzene, steroid
hormones)
Small polar molecules: water, urea, glycerol
Large polar molecules: sugars, nucleotides, amino
acids (don’t really get through)
Charged ions: H+, K+, Cl-, Na+, Ca++
- Membrane proteins convey specific permeability to a bilayer
oPolar molecules and ions must get help from membrane transport proteins to cross the
plasma membrane; transmembrane proteins act as selective entries, composing of 10%
of total human proteins. There are different types of membrane transport proteins
(carriers, pumps, ion channels, etc.)
oEx: bacterial lactose permease mutant showed that very specific transport proteins
existed; lactose wasn’t allowed in, but glucose and galactose could enter cell
oEx: human cystinuria mutant shows that cells can’t transport certain AAs like cystine
(dimer of cysteine) out of the urine or intestines into the blood. These accumulate as
kidney stones
- Basic types of transport mechanisms
oPassive transport: transport down a concentration gradient
Simple diffusion
Ion channel
Carrier proteins, transporters (glucose)
oActive transport: transport up a concentration gradient; uses energy
Pump
- Electrochemical gradient (membrane potential)
oAverage cell is -70 mV; if cell membrane is 3.5 nm thick, this provides 200,000 V/cm of
energy to do work
oIn passive transport:
For uncharged molecules, only the concentration matters
For charged molecules, both concentration and charge matter
oSince the inside of the cell is negatively charged, favors entry of Na+ ions into the cell
and opposes entry of Cl- ions into the cell
- Na+ K+ ATPase controls many cell activities (active transport)
find more resources at oneclass.com
find more resources at oneclass.com
oSets up 10% of the electrochemical gradient; drives import of many substances
oPumps 3 Na+ out for every 2 K+ in; uses ATP to do so
oResults in Na+ concentration of 145mM outside and 15mM inside. K+ concentration of
5mM outside and 140 mM inside cell. Difference produces chemical gradient and
electrical gradient, setting up electrochemical gradient
oCell activities the ATPase controls
Controls ion concentration of cell
Helps control membrane potential across the plasma membrane
Controls the cell’s volume
Drives active transport of amino acids, sugars, and nucleotides
A third of the average cell’s energy fuels the ATPase
For the brain, 2/3 energy of neuronal activity depends on fluxes of Na+/K+
oHow ATP drives transport
Features
1) ATPase has 2 different subunits. One is 100 kDa (transmembrane protein) and
the other is 45 kDa (associated transmembrane protein)
2) the 100 kDa subunit has multiple transmembrane domains
3) the 100 kDa subunit has binding sites for Na+, K+, ATP and ouabain
4) Ouabain is an inhibitor that binds to K+ site so K+ cannot cross membrane
5) For every cycle of 3Na+ out and 2K+ in, ATP split to ADP and phosphate group
o100 ATP split per second (300 Na+ out and 200 K+ in per second)
oA. Setting up an ion gradient
phosphorylation and
dephosphorylation are automatic:
autophosphorylation in step 2 and
autodephosphorylation in step 4;
drive conformational change
oB. Controlling cell’s volume
Normally, Na+ kept at
low concentration inside the cell by
the Na+/K+ ATPase
If the ATPase is
blocked by ouabain, then Na+
quickly goes to high concentrations
in the cell by flowing through different transmembrane proteins. Na+ concentrations
inside the cell is high, causing water to move into the cell by osmosis, and cell bursts
oC. Driving active import of sugars, amino acids, and nucleotides, etc.
ATP used to set up electrochemical gradient (Na+ 145mM out/15mM in)
The energy stored in the Na+ gradient drives the transport of other molecules
Ex: glucose transporter protein in the gut and kidney uses energy stored in
electrochemical gradient to transport a little glucose up its concentration gradient
with 2x amount of Na+ flowing down its concentration gradient (2 Na+ / 1 glucose)
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Due to hydrophobic interior, lipid bilayer surrounding cells and organelles acts as a highly impermeable barrier to most water-soluble (polar) molecules: mechanisms evolved mediated by special transmembrane proteins to take up nutrients, secrete waste, and transport molecules. Simple diffusion: given enough time, any molecule will cross membrane: rate at which this occurs depends on size and solubility in hydrophobic environment, from fast to slow: Oxygen, nitrogen, and carbon dioxide can cross. Large polar molecules: sugars, nucleotides, amino acids (don"t really get through) Charged ions: h+, k+, cl-, na+, ca++ Membrane proteins convey specific permeability to a bilayer: polar molecules and ions must get help from membrane transport proteins to cross the plasma membrane; transmembrane proteins act as selective entries, composing of 10% of total human proteins. Basic types of transport mechanisms: passive transport: transport down a concentration gradient. Carrier proteins, transporters (glucose: active transport: transport up a concentration gradient; uses energy.
