Physiology Muscle Weakness Membrane Transport

Front 1

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

Back 1

w

Front 2

understand the catalytic cycle of Na/K atpase and know similarities and diff of it to Ca atpase

Back 2

w

Front 3

specific drugs that inhibit p-type atpases

Back 3

w

Front 4

wilsons and multidrug resistance/ new atpase transporters

Back 4

w

Front 5

descr the basic secondary active transport mechanism (alt access model)
co transporters
Counter transporters

Back 5

w

Front 6

what are the two main classes of transport proteins?

Back 6

Carrier proteins and channel proteins

Front 7

Carrier proteins

Back 7

carriers/permeases/transporters
BIND solute and undergo conf change

2 classes:

Primary active:NA K atpoase
Secondary Active: NA/CA exchange

Front 8

Channel proteins

Back 8

do NOT really bind substrates

Front 9

Name the three vital P-Type atp-ases

Back 9

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

Front 10

Name the three primary active transporters

Back 10

Non-heavy metal transporters

Heavy metal transporters

ABC (ATP binding cassette) transporters

Front 11

Primary active transporters

catalytic subunit (alpha) has two parts

Back 11

1) alpha helices that traverse mem
2) large cytosol part (bulk of enz)
has three domains
P (phos)
N (nt binding)
A (actuator)

Front 12

Na/K-ATPase aka the Na pump

Back 12

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)

Front 13

Describe E1 of the Na/K pump

Back 13

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

Front 14

Describe the E2 state of the Na/K pump

Back 14

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

Front 15

explain osmotic balance through the Na pump

Back 15

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

Front 16

Ca-ATPase pump
high or low Ca in cell
name the two primary active transporters
how many Ca's pumped per ATP

Back 16

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

Front 17

Post albers E1 E2 transport cycle of Ca

Back 17

E1 + 2Ca --> E1*2Ca
--> E1 ATP 2Ca -->E1-P 2Ca --> --> E2P --> E2 -(spontaneous)->E1 (low E)

Front 18

Ca binding E1
water problem

Back 18

(-) 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!

Front 19

ATP binding to E1-Ca

Back 19

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

Front 20

Cation dissocation from E2

Back 20

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

Front 21

H/K atpase (proton pump)

Back 21

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

Front 22

Omeprazole -

Back 22

inhibits activity of proton pump

Front 23

Wilsons disease

Back 23

AR disease of copper metabolism

Front 24

Menkes disease

Back 24

inborn Cu deficiency, high [Cu] in organs damages liver and CNS, cirrhosis, mottor problems and psych disturbances

Front 25

MDR ATP-ases

Back 25

multi-drug resistance
ABC transporter
pg 199

Front 26

Secondary active transport
what is it?/ how different from primary?
2 types

Back 26

two or more molecule mvmt is coupled, ATP NOT used directly

2 types cotransport
countertransport

Front 27

Cotransport
dir of solute flow?
3 ex?

Back 27

all solutes in same dir
ex) Na/gluc
Na aa
Na/K 2Cl

Front 28

Na gluc and Na aa
location
binding sites
specificity

Back 28

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

Front 29

Na/K Cl transporter
important location

Back 29

important in kidney and intestine

Front 30

CounterTRansport

Back 30

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

Front 31

cardia glycosides

Back 31

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

Front 32

Ca overview

Back 32

E1, calcium binds
E1*Ca ATP binds
clam shell closes(water leaves)
E2P Ca leaves
E2 phosphate leaves
E1