chapter 13 Flashcards
(55 cards)
pumps
use a source of ree energy such as atp or light to drive thermodynamically uphill transport of ions or molecules (active transport
channels
enable ions to flow rapidly through membranes in a downhil direction (passive/faciliatited transport)
3 type of pumps
- p-type ATPase
- atp binding casette (abc) transporters
- secondary transporters
2 energy sources for pumps
atp or concentration gradient
p-type atpases
use atp to drive active transport of a specific ion
3 p-type atpases
ca2+ atpase: transports calcium from cytoplasm to sarcoplasmic reticulum of muscle cells
2. H+ K+ atpase enzyme responseible for pumping sufficient protons into the stomach to lower the pH below 1.0
- na+ k+ atpase - pumps na+ out of the cell and k+ into the cell
structure of sarcoplasmic reticulum ca2+ ATPase (SERCA)
110-kd polypeptide with a transmembrane domain consisting of 10
ALPHA helices. transmembrane domaine includes sites for binding 2 calcium ions. each calcium ion is coordinated to 7 oxygen atoms
3 domains: N binds atp nucleotide, P accepts phosphoryl group on aspartate residue, and A serves as an actuator for N domain
what does SERCA do?
maintains a calcium ion concentration of about .1 mM in the cytosol compared with 1.5 mM in the sarcoplasmic reticulum
what is muscle contraction and relaxation triggered by?
contraction: Abrupt rise in cytosolic calcium level. relaxation depends on rapid removal of ca2+ from cytosol into sarcoplasmic reticulum
sarcoplasmic reticulum:
contains large stores of calcium
what happens to SERCA after atp hydrolysis
N and P domains move toward one another during catalytic clycle. closure is facilitated by atp binding and binding of ca2+ to the membrane spanning helices
what happens when a phosphoryl analog binds, but no calcium
very different compared to structure without atp but with calcium
simple pump action mechanism
pump interconverts between 2 conformational states, each with a binding site acccessible to a different side of the membrane
serca mechanism
- atp binds into n domain, atp cleaved to adp, clacium is released
finally calcium goes back in
digitalis
plants that inhibit na+ K+ pump. digitoxigenin and ouabain are membres of this class as inhibitors
they inhibit dephosphorylation of ep-2 form of the atpase when applied on the extracellular face of the membrane.
digitoxigenin and ouabain are known as?
cardiotonic streoids becasue of their strong effects on the heart
how is digitalis used for congestive heart failure
increases force of contraction of heart muscle. inihibition of the na k+ pump leads to higher Na+ inside the cell. this risults in slower extrusion of CA2+ by sodium calcium exchanger. increase in intracellular level of ca2+ enhances contractility of cardiac muscle
multidrug resistance
tumor cells in culture often becoem resistant to drugs that were intialy quite toxic to the cells. development of resistance to one drug also makes the cells less sensitive to a range of other compounds
what causes multidrug resistance
multidrug resistance protein acts as an atp dependent pump that extrudes a wide range of small molecules from cells that express it. when cells are xposed to the drug, the MDR pumps the drug out of the cell before the drug can exerti ts effects
common architecture of MDR and homologous proteins
each protein has 4 domains: 2 membrane binding domains and 2 atp binding domains (abc transporters atp binding casettes). they are members of the p-loop NTPase super family
bacterial abc transporters are usually what compared to eukaryotic ones?
Bacterial ABC transporters are usually multimeric whereas
eukaryotic ones are monomeric
Mechanism of abc transporter mechanism
- opening of channel toward inside of teh cell
- substrate binding and conformational changes in the atp-binding casettes
- atp binding and further conformational changes
- speapartion of the membrane binding domains and relase of the substrate to the other side of the membrane
- atp hydrolysis to reset the transporter to its intitial state
how do abc transporters differ from p-type atpases?
different mechanism
what is a secondary transporter
membrane proteins that pump ions or moelcules uphill by coupling with the dowhill flow of a different species