Lecture 6 - iowacellbiologyspring2011

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Lecture 6
1. General types of membrane transport
a. Passive transport
i. Transport of a solute down its electrochemical energy gradient
1. [High]  [Low}
ii. Non-directional
1. Solute can move in either direction depending of
electrochemical gradient
iii. Glucose Transporter (GLUT1)
1. Plasma membrane Uniporter that catalyzes movement of
glucose down its concentration gradient.
2. Shuttles between two conformation states
3. Glucose binding site alternately faces outward and inward
4. Kinetics: Rate can saturate
5. Michaelis menton (1/2 Vmax)
6. Can be blocked by specific inhibitors
7. Rate of glucose can be lowered
b. Active Transport
i. Moves solutes up concentration or electrochemical gradient
ii. Always requires input of energy
1. From ion gradient
2. ATP hydrolysis
3. Light
iii. directional
1. Usually transports a given solute only in one direction
across the membrane
iv. Major functions in cells and organelles
1. Provides for uptake of essential nutrients even when their
concentration in the environment is much lower than in the
cell or organelle.
2. Allows various substances to be removed even when the
concentration is much greater outside the cell or organelle
3. Enables cell or organelle to maintain constant nonequilibrium concentrations of specific ions (K+, Na+, Ca++,
H+)
c. Types of Active Transport
i. Indirect Active Transport
1. Co-transport of two substrates
2. One substrate moves down its energy gradient
a. Usually an ion
i. Na or H
ii. Drives the movement of the other substrate
up its energy gradient
b. Example: Na+-glucose symporter
ii. Anti-transport of substrates
1. Only one substrate can bind at a time
2. Transporter re-orients only if substrate bound
3. No re-orientation if transporter empty
4. Example: Na+/H+ Antiporter
a. Controls pH in cells
d. Direct Active Transport
i. Movement of solute coupled directly to a chemical reaction
1. Usually ATP hydrolysis
ii. At least 4 general types of transport ATPases:
1. P-class
a. H, Na, K, Ca 2+
b. Alpha subunits (2) phosphorylated during solute
transport
c. Smaller Beta subunits regulate transport
d. Locations
i. Plants, fungi, bacteria
1. Plasma membrane
2. H+ pump
ii. Higher Eukaryotes
1. Plasma membrane
2. Na+/K+ pump
iii. Mammalian Stomach Cells
1. Apical Plasma Membrane
2. H+/K+ pump
iv. All Eukaryotic Cells
1. Plasma Membrane
2. Ca 2+ pump
v. Muscle Cells
1. Sarcoplasmic Reticulum membrane
2. Ca 2+ pump
3. Example: Na+-K+-ATPase
a. Active Transport mediated by a
carrier protein
b. Found in an Animal cell plasma
membranes
c. 3 Na+/2 K+ transported per
ATP molecule hydrolyzed
d. Na goes to extracellular space
e. Electrogenic
f. 100 molecules ATP/sec
2. F-Class
a. H+ only
b. Multiple Transmembrane and Cytosolic Subunits
c. Synthesize ATP on Beta Cytosolic subunits
d. Powered by movement of H+ down an
electrochemical gradient
e. Locations
i. Bacterial Plasma membranes
ii. Inner mitochondrial membrane
iii. Thylakoid membrane of chloroplast
3. V-Class
a. H+ only
b. Multiple Transmembrane and Cytosolic Subunits
c. Energy released by ATP hydrolysis used to pump H+
ions from cytosol to organelle lumens, acidifying
them
d. Protein doesn’t become phosphorylated
e. Locations
i. Plants, yeast, other fungi
1. Vacuolar Membranes
ii. Animal Cells
1. Endosomal and lysosomal membrane
in animal cells
iii. Acid-Secreting Animal Cells
1. i.e. osteoclasts and some kidney
tubule cells
2. excreted as urine
3. Plasma Membrane
4. ABC Class (superfamily)
a. Ions and various small molecules
i. Amino Acids
ii. Sugars
iii. Inorganic ions
iv. Polysaccharides
v. Peptides
vi. Proteins
b. 2 Transmembrane domains form the pathway for
c.
d.
e.
f.
solute.
Two Cytosolic ATP-binding domains
Couple ATP hydrolysis to solute movement
Domains may be in one or separate subunits.
Locations
i. Bacterial plasma membranes
1. Transports
a. Amino acids
b. Sugar
c. Peptide
ii. Mammalian Endoplasmic reticulum
1. Transports
a. Peptides associated with
antigen presentation by MHC
proteins.
iii. Mammalian Plasma Membranes
1. Transports
a. Small molecules
b. Phospholipids
c. Small lipid like drugs
g. Uses
i. Cancer
1. Multidrug Resistance Protein (MDR)
ii. Malaria
1. Parasite Plasmodium develops
resistance to anti-malarial drugs by
upregulating ABC transporters
iii. Cystic Fibrosis
1. Cystic Fibrosis Transmembrane
Conductance Regulator CFTR
iv. Functions as a Cl- channel in plasma
membrane of epithelial cells
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