Rbc Membrane

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.

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To achieve this task the red cell should be capable of traversing the microvascular system without mechanical damage,

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and that the cell should retain a shape which facilitates gaseous exchange.

Red cell membrane 

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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 To

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.

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 

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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Phospholipids are fat derivatives in which one fatty acid has been replaced by a phosphate group and one of several nitrogen-containing molecules.

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Phospholipid molecules are characterized by a polar head group attached to a nonpolar fatty acid tail.

Membrane Phospholipids 

The polar head group is hydrophilic (water loving)

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The charges on the phosphate and amino groups make that portion of the molecule hydrophilic

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The fatty acid tail(Hydrocarbon chains) is hydrophobic (water fearing).

RBC Membrane Phospholipids 

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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.

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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.

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The cholesterol molecule inserts itself in the membrane with the same orientation as the phospholipid molecules.

Membrane Cholesterol

Membrane Cholesterol 

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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

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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 Glycophorin labled • coomassie blue indicating it is exposed B, drawing of the positions on theproteins outer surface of some major 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  

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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

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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 proteinBand3

Red Cell Membrane Proteins

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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.... 

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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 o o o

BAND 3 It is a single molecule with a molecular weight of 95000. It accounts for 25% of total protein content of the RBC membrane. 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 

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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 

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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 

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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 

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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 

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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  

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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   

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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

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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 

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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.