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BCHOBI 812

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Digitalis inhibits pump by blocking K -activated dephosphorylation: Molecular mechanism for Na /K transport: The formation of a b-aspartyl ... – PowerPoint PPT presentation

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Title: BCHOBI 812


1
BCH/OBI 812 September 19, 2002 C. Waechter
MEMBRANE CHANNELS AND PUMPS Stryer-Chapter 13
Sodium Pump a Na/K-ATPase Structure
Heterotetramer a 112 kDa-8 TMDs b 35 kDa
2
Molecular mechanism for Na/K transport The
formation of a b-aspartyl phosphoryl intermediate
causes a conformational change in the pump
everting the Na- binding site to face the
outside of the cell.
(P-type ATPase)
Digitalis inhibits pump by blocking K-activated
dephosphorylation
Loss of sodium gradient increases intracellular
calcium ions which increases force of
contraction Used to treat congestive heart
failure
3
The sarcoplasmic reticulum (SR) Ca-ATPase pumps
calcium ions into the SR by a mechanism similar
to the sodium pump.----a single 110 kDa
polypeptide Another P-type ATPase
4
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5
Active versus passive transport Calculation
of free energy change(Stryer-p. 347)
C1
C2
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
6
The electrochemical gradient created by the
sodium pump can be used for the active
transport of glucose via the Na/glucose symporter
7
Antiporters and symporters are two basic types of
secondary transport sytems
The sodium/calcium exchanger in the plasma
membrane of animal cells is an example of an
antiporter
8
Lactose permease in E. coli is an example of a
symporter utilizing the free energy of the proton
gradient across the cytoplasmic membrane
(symporter)
9
Acetylcholine Receptor structure and function as
a channel (Stryer-p. 355)
10
(Heteropentamer)
11
Sodium Channel A voltage-gated channel with 24
transmembrane helices that was first isolated as
a tetrodotoxin receptor. Structure has four
repeating units (I-IV) S1, S2, S3, S5 and S6 are
hydrophobic segments and S4 is highly positive
with many Arg and Lys residues which serves as
the voltage sensor.
12
Potassium channels are homologous to sodium
channels Two site model for rapid rates in
potassium channel K ejected by electrostatic
repulsion--------
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