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Red cell membrane

Alick Mwambungu
Red cell membrane
 The primary function of the red cell is the
transport of respiratory gases to and from
the tissues.

 To achieve this task the red cell should be


capable of traversing the microvascular
system without mechanical damage,

 and that the cell should retain a shape


which facilitates gaseous exchange.
Red cell membrane
 In order to meet with the demands of
function, the red cell membrane should be
extremely tough yet highly flexible.
 This strength and flexibility of the red cell
membrane is due to the design of its
protein cytoskeleton and the way the
cytoskeleton interacts with the membrane
lipid bilayer.
Functions of red cell membrane
o Toseparate the contents of the cell
from the plasma.
To maintain the characteristic shape of
the red cell.
To regulate intracellular cation conc.
To act as the interface between the cell
and its environment via membrane
surface receptors.
Red cell membrane
 The red cell membrane consists of:
Proteins~50%
Lipids ~ 40%
Carbohydrates~10%
General structure of a Cell Membrane
Composition of the red cell membrane

MEMBRANE CARBOHYDRATES

 They occur only on the external surface of


the red cell.
 They occur as glycoprotein and glycolipids.
 The antigens of the ABO blood group are
examples of membrane carbohydrates.
Composition of the RBC memb. (cont.)

Membrane Lipids
Lipid components of the red cell
membrane are:
30% free unesterified cholesterol.
10% Glycerides and free fatty
acids.
60% Phospholipids
Membrane Phospholipids

 Phospholipids are fat derivatives in which


one fatty acid has been replaced by a
phosphate group and one of several
nitrogen-containing molecules.

 Phospholipid molecules are characterized


by a polar head group attached to a non-
polar fatty acid tail.
Membrane Phospholipids

 The polar head group is hydrophilic


(water loving)

 The charges on the phosphate and amino


groups make that portion of the molecule
hydrophilic

 The fatty acid tail(Hydrocarbon chains) is


hydrophobic (water fearing).
RBC Membrane Phospholipids
 Thus the phospholipids in the cell
membrane tend to arrange themselves in
a bilayer.
 Hydrophilic heads pointing towards the
inner and outer aqueous phases ( the
cytoplasmic and extracellular phase),
 The hydrophobic tails point towards each
other.
 The red cell membrane phospholipids,
are: Phosphatidyl choline(Lethicin),
Phosphatidyl ethanolamine,
Sphingomyelin and Phosphatidyl serine
Phosphatidyl ethanolamine
Phosphatidyl Serine
RBC Membrane Phospholipids

 The choline phospholipids-Phosphatidyl


choline and sphingomyelin are mainly
present in the extracellular layer.

 Amino phospholipids-Phosphatidyl
ethanolamine and phosphatidyl serine are
restricted to the cytoplasmic layer.
Membrane Cholesterol

 The membrane cholesterol is


unesterified and lies between the two
layers of the lipid bilayer.

 The cholesterol molecule inserts itself


in the membrane with the same
orientation as the phospholipid
molecules.
Membrane Cholesterol
Membrane Cholesterol

 The concentration of cholesterol in the


membrane is an important determinant of
membrane surface area and fluidity.
 An increase in membrane cholesterol
leads to an increased surface area and
decreased deformability.
 In extreme circumstances, decreased
deformability can lead to premature RBC
destruction.
Composition of the red cell

Membrane Proteins
 These are either:
-Peripheral or
-Integral
Membrane Proteins

 RBC membrane proteins have been


named according to their relative
positions on SDS-PAGE electrophoresis
SDS-PAGE separation of red
blood cell proteins after

A, gel stained with


• coomassie Glycophorin
blue labled
indicating it is
exposed
B, drawing of the positions
on theproteins
of some major outer surface
of the
membrane
Red cell membrane proteins
Peripheral Proteins
 The red cell peripheral proteins interact to
form a cytoskeleton.
 The cytoskeleton acts as a tough
supporting framework for the lipid bilayer.
 Four peripheral proteins play a key role in
the structure of the red cell cytoskeleton:
- Spectrin
- Ankyrin
- Protein 4.1 and
- Actin
Red Cell Membrane
Red cell membrane proteins
Spectrin(Bands 1 and 2)
 Is the most abundant membrane protein
 consists of two chains, α and β, wound
around each other to form heterodimers
which then self-associate head to head to
form tetramers.
 These tetramers are linked at the tail end
to actin and are attached to protein band
4.1.
 At the head end, the β-spectrin chains
attach to ankyrin which connects to band
3(anion channel). Protein 4.2 enhances
this interaction.
Red Cell Membrane Proteins

Ankyrin(Bands 2.1-2.3)
 This serves to anchor assembled spectrin
molecules to the lipid bilayer.
 Accomplished by binding simultaneously
to the spectrin tetramers and to the
interior domain of the integral protein-
Band3
Red Cell Membrane Proteins

Actin(Band 5)
 It is a globular protein
 Composed of filaments
 The filaments bind weakly to the tail end
of both α and β spectrins.
Red Cell Membrane proteins

Band 4.1
 It’s a globular protein

 Binds to spectrin close to the actin


binding site thereby strengthening
and stabilizing the cytoskeletal
lattice.
Band 4.1 Cont....
 Also binds directly to Glycophorins A
and C and Band3.
 It therefore strengthens the links
between the lipid bilayer and the
protein cytoskeleton.
Red cell membrane proteins

Integral Proteins

 These penetrate the lipid bilayer and are


firmly anchored within it.
-Band 3
-Glycophorins A, B, and C.
-Na+/K+ ATPase.
-glucose transport protein.
-surface receptors.
Red cell membrane proteins
BAND 3
o It is a single molecule with a molecular
weight of 95000.
o It accounts for 25% of total protein
content of the RBC membrane.
o Has two major functions within the red
cell membrane:
1-To facilitate anion transport via the
red cell membrane.
2- It is an important binding site for
cytoskeletal and other red cell proteins.
Red Cell Membrane
Glycophorins
 Three members of the RBC glycophorin
family:
 Glycophorins-A,B and C
 These are sialoglycoproteins.
 A sialoglycoprotein is a combination of
sialic acid and glycoprotein (which is,
itself, a combination of a sugar and
protein)
Red Cell Membrane Proteins

 Glycophorins act as transmembrane


signal transducers.
 Also acts as the receptor for the
Plasmodium falciparum protein PfEBP-2
(erythrocyte binding protein 2)
Red cell membrane proteins
Na+/K+ ATPase
 This enzyme catalyses the hydrolysis of
ATP to ADP, liberating energy in this
process.
 Each ATP molecule hydrolysed via this
system results in the ejection of three Na+
ions from the cell and the transport of two
K+ ions into the cell.
Na/K ATPase pump Mechanism
Na/K ATpase pump Mechanism
 The pump, with bound ATP, binds 3
intracellular Na+ ions.
 ATP is hydrolyzed, leading to
phosphorylation of the pump and
subsequent release of ADP.
 A conformational change in the pump
exposes the Na+ ions to the outside.
 The phosphorylated form of the pump has
a low affinity for Na+ ions, so they are
released.
Na/K ATpase Pump
 The pump binds 2 extracellular K+ ions. This
causes the dephosphorylation of the pump,
 reverting it to its previous conformational
state, transporting the K+ ions into the cell.
 The unphosphorylated form of the pump
has a higher affinity for Na+ ions than K+
ions.
 the two bound K+ ions are released. ATP
binds, and the process starts again.
Glucose transport Protein

 Has a molecular weight of 60 000.


 ATP hydrolysis not required for Glucose
transport
 Motive force for transport of plasma
Glucose into the red cell is derived from
the electrochemical gradient of Na+ ions
across the cell membrane.
Membrane Proteins
 Each molecule of Glucose transported into
the cell is accompanied by a Na+ ion
 Leading to a net reduction in the
transmembrane gradient of Na+ ions.
 Failure of the cation pump to regenerate
the Na+ gradient ,would result in failure
of Glucose transport.
 May lead to glycolytic failure and hence
lack of ATP generation.
 Final result-cell death.
Surface receptors
 Most important surface receptor is
transferrin receptor.
 Though present on most of the cells
 The highest conc is on RBC surface.
 The receptor domain is capable of binding
two transferrin molecules.
 Receptor-transferrin complexes are
internalised.
 Iron released from the transferrin
Blood group antigens

o These are antigens found on the red cell


membrane, they are responsible for the
determination of the blood group of the
individual.
 Blood group antigens are found on both
the protein and the carbohydrate
components of the membrane
glycoproteins and the glycolipids.
Abnormalities of the RBC
membrane
 Hereditary sherocytosis-Decrease in
surface area to volume ratio.
 May be as a result of defective
cytoskeletal proteins.
 Hereditary Elliptocytosis-Abnormal
membrane cholesterol distribution or
Abnormalities in the α or β spectrin
subunits.