rbc membrane
DESCRIPTION
The author is a Lecturer at Ndola Colege of Biomedical Sciences.TRANSCRIPT
![Page 1: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/1.jpg)
Red cell membrane
Alick Mwambungu
![Page 2: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/2.jpg)
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.
![Page 3: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/3.jpg)
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.
![Page 4: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/4.jpg)
Functions of red cell membrane
oTo separate 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.
![Page 5: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/5.jpg)
Red cell membrane
The red cell membrane consists of: Proteins~50% Lipids ~ 40% Carbohydrates~10%
![Page 6: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/6.jpg)
General structure of a Cell Membrane
![Page 7: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/7.jpg)
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.
![Page 8: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/8.jpg)
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
![Page 9: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/9.jpg)
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.
![Page 10: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/10.jpg)
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).
![Page 11: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/11.jpg)
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
![Page 12: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/12.jpg)
Phosphatidyl ethanolamine
![Page 13: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/13.jpg)
Phosphatidyl Serine
![Page 14: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/14.jpg)
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.
![Page 15: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/15.jpg)
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.
![Page 16: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/16.jpg)
Membrane Cholesterol
![Page 17: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/17.jpg)
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.
![Page 18: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/18.jpg)
Composition of the red cell
Membrane Proteins These are either: -Peripheral or -Integral
![Page 19: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/19.jpg)
Membrane Proteins
RBC membrane proteins have been named according to their relative positions on SDS-PAGE electrophoresis
![Page 20: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/20.jpg)
A, gel stained with • coomassie blue
B, drawing of the positions of some major proteins
SDS-PAGE separation of red blood cell proteins after
Glycophorin labled indicating it is exposedon the outer surface of themembrane
![Page 21: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/21.jpg)
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
![Page 22: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/22.jpg)
Red Cell Membrane
![Page 23: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/23.jpg)
Red cell membrane proteins
Spectrin(Bands 1 and 2) Is the most abundant membrane protein consists of two chains, and , 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 -spectrin chains attach to ankyrin which connects to band 3(anion channel). Protein 4.2 enhances this interaction.
![Page 24: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/24.jpg)
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
![Page 25: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/25.jpg)
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 and spectrins.
![Page 26: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/26.jpg)
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.
![Page 27: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/27.jpg)
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.
![Page 28: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/28.jpg)
![Page 29: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/29.jpg)
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.
![Page 30: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/30.jpg)
Red cell membrane proteins
BAND 3o 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.
![Page 31: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/31.jpg)
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)
![Page 32: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/32.jpg)
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)
![Page 33: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/33.jpg)
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.
![Page 34: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/34.jpg)
Na/K ATPase pump Mechanism
![Page 35: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/35.jpg)
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.
![Page 36: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/36.jpg)
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.
![Page 37: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/37.jpg)
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.
![Page 38: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/38.jpg)
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.
![Page 39: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/39.jpg)
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
![Page 40: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/40.jpg)
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.
![Page 41: RBC Membrane](https://reader033.vdocuments.us/reader033/viewer/2022061116/54660418b4af9f14548b46a8/html5/thumbnails/41.jpg)
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 or spectrin subunits.