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32 Cards in this Set

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Describe how energy from ATP hydrolysis is used by P-Type, primary active ATPases to transport ions such as sodium potassium and calcium across membranes
w
understand the catalytic cycle of Na/K atpase and know similarities and diff of it to Ca atpase
w
specific drugs that inhibit p-type atpases
w
wilsons and multidrug resistance/ new atpase transporters
w
descr the basic secondary active transport mechanism (alt access model)
co transporters
Counter transporters
w
what are the two main classes of transport proteins?
Carrier proteins and channel proteins
Carrier proteins
carriers/permeases/transporters
BIND solute and undergo conf change

2 classes:

Primary active:NA K atpoase
Secondary Active: NA/CA exchange
Channel proteins
do NOT really bind substrates
Name the three vital P-Type atp-ases
P-Type ATPases: a large family of related proteins that transport ions, most usually cations, across biological membranes in nearly all species

Na/K
Ca
H/K
also under the non-heavy metal transporters
Name the three primary active transporters
Non-heavy metal transporters

Heavy metal transporters

ABC (ATP binding cassette) transporters
Primary active transporters

catalytic subunit (alpha) has two parts
1) alpha helices that traverse mem
2) large cytosol part (bulk of enz)
has three domains
P (phos)
N (nt binding)
A (actuator)
Na/K-ATPase aka the Na pump
in virtually every cell
for every ATP pumps 3 Na out and 2 K in
electrogenic (moves more pos out of the cell than in

Inhibited by:
cardia glycosides(steroids) ouabain and digitalis)
Describe E1 of the Na/K pump
E1 - LOW energy state, has Na binding sites, is open to the Cytosol
steps:
E1 + ATP
E1-P*(Na)3 (high energy)
ATP hydrol->P of the alpha subunit -> conf change and Na is encased

E2-P?: ECM side opens
Describe the E2 state of the Na/K pump
E2 - has K binding site, is open to the ECM

Steps:
E2-P + 3 Na (with ECM side open)( low affinity ) --> Na leaves

2 K from ECM bind E2-P ( high affinity)

P leaves E2 encases K (high energy conformation)

ATP binds E2 returns it to E1 (LOW affinity, K in E1) and K is released
explain osmotic balance through the Na pump
neg charged anions in cytosol, accompanying cations to balance this draw water into the cell,
is Na out of cell and accompanying Cl- kept out my mem pot
Ca-ATPase pump
high or low Ca in cell
name the two primary active transporters
how many Ca's pumped per ATP
LOw inside cell
two primary active transporters
PM (plasma mem)(calmodulin binding to C terminus)
SR (moves Ca into organelles)

1-2 Ca per ATP
Post albers E1 E2 transport cycle of Ca
E1 + 2Ca --> E1*2Ca
--> E1 ATP 2Ca -->E1-P 2Ca --> --> E2P --> E2 -(spontaneous)->E1 (low E)
Ca binding E1
water problem
(-) charged aa's in the alpha helix have high affinity for Ca when exposed to cytosol, lots of water in the cation binding vestibule, cations are surrounded by water, need to strip it in order to get through the plasma membrane, water carries cations to aa residues, ATP binds, causing M1 to get bent in half and pushes the water out

in occluded state no water!
ATP binding to E1-Ca
closes the three domains (A N P)

A pulls on M1 and M2 displacing water and trapping Ca in mem. N domain closes in on the P domain, so asp can be P'd by ATP
Cation dissocation from E2
The major E1 to E2 conformational transition disrupts Ca coordination


alpha helices undergo twisting in the E2 form to completley disrupt the Ca binding sites, twists make E2 a low affinity binding for Ca therefore it will be released
H/K atpase (proton pump)
found in parietal cells(HCl)

60% seq ID with Na/K
both have beta subunit vital for targeting of the pump to the Plasma Membrane
Omeprazole -
inhibits activity of proton pump
Wilsons disease
AR disease of copper metabolism
Menkes disease
inborn Cu deficiency, high [Cu] in organs damages liver and CNS, cirrhosis, mottor problems and psych disturbances
MDR ATP-ases
multi-drug resistance
ABC transporter
pg 199
Secondary active transport
what is it?/ how different from primary?
2 types
two or more molecule mvmt is coupled, ATP NOT used directly

2 types cotransport
countertransport
Cotransport
dir of solute flow?
3 ex?
all solutes in same dir
ex) Na/gluc
Na aa
Na/K 2Cl
Na gluc and Na aa
location
binding sites
specificity
location - luminal membraneof small intestines and proximal tubule
2 binding sites on ECM side (one for na and one for gluc
for Na aa, each protein (5) is responsible for a spec subset of aa's based on molecular specificity

SEE PAGE 200
Na/K Cl transporter
important location
important in kidney and intestine
CounterTRansport
solutes move in opp dir

ex) Na/Ca - downhill mvmt of na into cell drives Ca out of cell, 3 Na for each Ca, ELECTROGENIC - 3 pos enter cell, 2 pos leave it

and Na/H - inward mvmt of 1 Na , outward mvmt of 1 H
cardia glycosides
inhibit the sodium pump, increase Na on inside.
ouabain and digitalis
changes sodium gradient
change the driving force for Ca expulsion out of cardiac myosite
Ca overview
E1, calcium binds
E1*Ca ATP binds
clam shell closes(water leaves)
E2P Ca leaves
E2 phosphate leaves
E1