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Cell membrane, transport
Prof. Gábor Szabó, 2017
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This lecture:
• Essential Cell Biology: chapters 11-12
All the pages are required, except:
• ion channels, the pumps and mechanisms relevant to
Ca, osmo- and pH regulation, also included in this
chapter of the book, will be discussed in other
lectures
• Text briefly describing the various membrane
transporters discussed in this lecture is
downloadable from our website! Together with the
- marked lecture slides, that text is
required material for the tests and exam!
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Keywords
• amphiphylic (amphipathic)
compounds
• lipid bilayer
• electrochemical gradient
• lipid-water partitioning
coefficient
• Henderson-Hasselbach equation
and its meaning
• facilitated diffusion
• carrier mediated passive
transport
• passive and active transport
• coupled transport (secondary
active) transport, examples of
(Na/glucose and Na/Ca)
• Na/K pump,
• glucose uniport
• P-type, V-type transporters
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Lipid
bilayer
5 nm
Functions of the
plasmamembrane:
barrier
transport
signal transduction
Composition:
40-60 % lipid
30-50 % protein
10 % carbohydrate
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Glycocalix
Glycolipids,
glycoproteins
Actin cell cortex
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Membrane proteins
RBC: ~50 membrane
proteins
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(„Gram-negative”) bacteria have two cell membranes
outer membrane: porins render it permeable
inner membrane: transporters
Lodish, Fig.
15-15
Alberts, Fig.
11-17
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Lipid synthesis and steady-state composition of cell membranes
Mitochondria
have bacterial
lipids.
Low cholesterol
in Mit/ER/NE
Nat. Rev. Mol. Cell. Biol. 2008
Major
differences
between
organelles
site of synthesis
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Asymmetric
lipid
composition
1. lipid incorporation into cytoplasmic leaflet
2. selective retention
3. flippases
/floppases
curvature
Asymmetric lipid
composition
scramblases
PS exposure on the surface of dying
cells: eat-me signal for the phagocytes
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Lipid shape and supramolecular organization (polymorphism).
Kai Simons, and Julio L. Sampaio Cold Spring Harb
Perspect Biol 2011;3:a004697
©2011 by Cold Spring Harbor Laboratory Press
curvature
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Cytosolic and exoplasmic surface
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Mobility may be restricted by clustering and molecular fences
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Examples of heterogenous distribution of proteins in the plasma
membrane of mammalian cells. (PMC5040727/figure/F4/)
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Cell 2015
Transbilayer lipid
interactions
mediate
nanoclustering of
lipid-anchored
proteins*.
*
!
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Intimate relationship with the cell cortex
RBC
Intracellular side
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Figure 4. Red cell morphology. Hereditary
spherocytosis (HS; top panel); nonhemolytic
hereditary elliptocytosis (HE; middle panel);
elliptocytes, poikilocytes, and fragmented red cells in
hemolytic HE (bottom panel). BLOOD, 2008, 112(10)
mutation
altered morphology
Cell shape is determined by the
cell cortex cytoplasm
Defects that interrupt the vertical spectrin interactions
are the biochemical and molecular basis for hereditary
spherocytosis (HS), whereas defects in horizontal
interactions cause hereditary elliptocytosis (ES).
BLOOD, 2008, 112(10)
ES
HS
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rso
isohypotony normotony
ghostRBC
Membrane fluidity - permeability, deformability,
regenerative capacity
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Transport
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Categories of membrane transport, according to…
→ Energetics
– passive
– active
→ Transported
substance
solubility
– hydrophylic
– hydrophobic
→ Membrane structure
– lipid bilayer
– complete biological
membrane
→ Number of different
transported
substances/direction of
transport
– uniport
– symport, antiport
1C
C
aq
m
>=R
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5-8
nm
Lipid bilayers (arteficial membranes)
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Vesicles and MBLs
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Hundertwasser,
Vienna
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Real membranes: passive and active transport
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Carrier-mediated - passive - transport
uniport ……. mechanism resembles that of
the ionophore Valinomycin
K+
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Main categories of active transport
symport antiport
P V F ABC
Na/K* Pgp,etc
vacuolar
mitochondrial
Secondary active
transporters, carriers
* The Na/K-ATPase is also
antiport by directionality, but it is
not a coupled/secondary active
transporter; it is a P-type pump.
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Intestinal glucose
transport
What do you expect to
occur as a result of
inhibiting the Na/K-
pump?
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Why is intestinal glucose transport unidirectional (rectified)?
Why do coupled transport processes depend on transmembrane Na+
gradient?
http://academic.brooklyn.cuny.edu/biology/bio4fv/page/sympo.htm
~ 30% of total energy consumption
in the cell!
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A rise in the intracellular Ca2+ concentration causes muscle cells
to contract. In addition to an ATPdriven Ca2+ pump, muscle cells
that contract quickly and regularly, such as those of the heart,
have an additional type of Ca2+ pump—an antiport that
exchanges Ca2+ for extracellular Na+ across the plasma
membrane. The majority of the Ca2+ ions that have entered the
cell during contraction are rapidly pumped back out of the cell by
this antiport, thus allowing the cell to relax. Ouabain and digitalis
are used for treating patients with heart disease because they
make heart muscle cells contract more strongly. Both drugs
function by partially inhibiting the Na+ pump in the plasma
membrane of these cells.
Can you propose an explanation for the effects of the drugs in the
patients? What will happen if too much of either drug is taken?
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Categories of transport according to
solubility of
„S”:
A. hydrophylic substrates
B. hydrophobic substrates
1C
C
aq
m
>=R
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Transport of hydrophobic molecules
• Passive
– R (lipid / water partition coeff.)
– i.c. partition - Henderson-Hasselbach eq.
• Active
– ABC (ATP binding casette) transporters
– Other transporters
pH = pK + log(M/M+)
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~lipid-water partition coeff.
~ m
inim
al
eff
ecti
ve c
c.
1. lipid-water partition
coeff. determines the efficiency
of general anaesthetics
P
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Conformation of proteins is sensitive to the
distribution of lateral pressure across the membrane
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ion
channels
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R-NH2
lysosome
pH ≈ 5cytoplasm
pH ≈ 7
R-NH2
R-NH3+
R-NH3+
The lipid-water partition coefficient may
be pH-dependent
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Daunorubicin distribution in cytoplasts
Selwyn J. Hurwitz et al. Blood 1997;89:3745-3754
©1997 by American Society of Hematology
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Live cells incubated simultaneously with
MitoTracker® Deep Red FM,
LysoTracker® Green DND-26, and
Hoechst 33342 (InvitrogenTM)