Red Blood Structure and Function

Question 1

Describe the structure of RBCs(4)

Answer 1

→Mammalian RBCs are biconcave disc-shaped.

→ have flexible membranes with a high surface-to-volume ratio.

→They are 8 microns in diameter but are able to deform and pass through capillaries or RES(reticuloendothelial system) without fragmentation.

→The RBC is unique amongst eukaryotic cells as it lacks a nucleus, mitochondria and ER, and its cytoplasm is essentially rich in haemoglobin.

Question 2

What are proportions of the components of RBCs?

Answer 2

o 50% Proteins
o 40% Lipids
o 10% Carbohydrates

Question 3

What is the primary function of RBCs and how does it achieve this?(4)

Answer 3

• Primary function of RBC is transport of respiratory gases to and from the tissues

2. • rbc traverse the microvascular system without mechanical damage and retain a shape which facilitates gaseous exchange.
3. the red cell membrane should be extremely tough yet highly flexible
4. Lacks mitochondria so it won’t use O2 molecules it carries

Question 4

Describe the three layers of lipid bilayer if RBCs

Answer 4

o An outer hydrophilic portion composed of glycolipids, glycoproteins, and
proteins

o A central hydrophobic layer containing proteins, cholesterol and phospholipids

o An inner hydrophilic layer of mesh-like cytoskeletal proteins to support lipid bilayer

Question 5

What are the lipid components if the red cell membrane?

Answer 5

 Phospholipids – 60%
 Cholesterol - 30%
 Sphingolipids – 10%

Question 6

Describe the structure of the membrane (4)

Answer 6

o Asymmetric phospholipid distribution.
o Unesterified free cholesterol between.

o Uncharged phospholipids of outer layer : (Phosphatidyl choline and Sphingomyelin)

o Charged phospholipids of inner layer: Phosphatidyl ethanolamine , Phosphatidyl serine

Question 7

Describe the cholesterol in the lipid membrane (3)

Answer 7

• Membrane cholesterol exists in free equilibrium with plasma cholesterol
• Membrane cholesterol is unesterified and lies between the two layers of the lipid bilayer
• The concentration of cholesterol in the membrane is an important determinant of membrane surface area and fluidity

Question 8

What does increases in membrane cholesterol result in?(3)

Answer 8

• Increase in membrane cholesterol leads to an increased surface area and decreased deformability.
• RBCs with increased cholesterol appear distorted resulting in acanthocytosis
• ▪ An increase in cholesterol and phospholipid is a cause of target cells

Question 9

What are the two major integral membrane proteins and what do they do?

Answer 9

A. Glycophorins: A, B, and C- are rich in sialic acid, which gives the red blood cells a very hydrophilic-charged coat. This enables them to circulate without adhering to other cells or vessel walls
B. Band 3: anion transporter, ion transport and maintenance of protein-protein interactions

Question 10

What are other integral proteins?

Answer 10

Na+/K+ ATPase, Aquaporin 1, surface receptors, e.g. TfR

Question 11

What is the role of glycophorins?(2)

Answer 11

the major integral membrane proteins, accounting for location of RBC antigens.

They impart –ve charge to cell, reducing interaction with other cells/endothelium

Question 12

Name 4 peripheral proteins

Answer 12

Spectrin, Ankyrin, Protein 4.1 and Actin

Question 13

What are peripheral proteins?(2)

Answer 13

Limited to cytoplasmic surface of membrane and forms the RBC cytoskeleton.

• Cytoskeleton acts as tough framework to support bilayer

Question 14

Describe the structure of spectrin

Answer 14

• The most abundant peripheral protein

* Composed of alpha & beta chains

Question 15

What is the role of spectrin?(4)

Answer 15

• Very important in RBC membrane integrity

2. binds with other peripheral proteins to form the cytoskeletal network of microfilaments
3. Controls biconcave shape and deformability of cell
4. If denatured red cell becomes spherical, loses flexibility

Question 16

What does ankyrin do?

Answer 16

• primarily anchors lipid bilayer to membrane skeleton, via interaction with spectrin and Band 3

Question 17

What does Protein 4. 1 do?(2)

Answer 17

• may link the cytoskeleton to the membrane by means of its associations with glycophorin
• stabilises interaction of spectrin with actin

Question 18

What does actin do?

Answer 18

o responsible for contraction and relaxation of membrane

Question 19

What are sulphydrl and what do they require to work?

Answer 19

essential for the maintenance of their tertiary structure and therefore the structural integrity of the red cell.

These sulphydryl groups require NADPH generated by the pentose phosphate pathway to protect them from oxygen radicals.

Question 20

How are carbohydrates attached to proteins and lipids?

Answer 20

glycosylation.

Question 21

Recall some carbohydrates that can be found on the cell surface

Answer 21

o Galactose, Mannose, Fucose, N-acetylgalactosamine, Glucuronic acid, Glucose, Sialic acid, N-acetylglucosamine

Question 22

Name some blood groups associated with specific membrane structures

Answer 22

 Many antigens are proteins: e.g. Rhesus, Duffy, Kidd
 Others are carbohydrates; e.g. ABO, Lewis
 Others are combination of glycolipids and proteins

Question 23

What are the functions of the cell membrane?

Answer 23

1. Provides the optimum surface area to volume ratio for respiratory exchange
2. deformability, elasticity allowing for passage through micro vessels (capillaries)
3. Regulates intracellular cation concentration.

4.Acts as the interface between the cell and its environment via membrane surface receptors.

5. Allows water and electrolytes to exchange via cation pumps.
6. RBC controls volume and H2O content primarily through control of intracellular concentrations of Na+ and K+ via these cationic pumps which require ATP.

Question 24

What is acanthocytes?

Answer 24

o RBCs with increased cholesterol appear distorted

Question 25

What is hereditary spherocytosis?(4)

Answer 25

 Ankyrin def or abnormalities
 A or B spectrin def or abnormalities
 Band 3 protein abnormalities
 Protein 4.2 abnormalities

Question 26

How does hereditary elliptocytosis arise?(3)

Answer 26

 A or B spectrin mutation – defective spectrin dimer
 A or B spectrin mutation – defective spectrin-ankyrin association
 Protein 4.1 deficiency or abnormalities

Question 27

How does the RBC withstand life without structural deterioration?

Answer 27

1. Geometry of cell; surface area to volume ratio: facilitates deformation whilst maintaining constant surface area.
2. Membrane deformability: Spectrin molecules undergo reversible change in conformation: some uncoiled and extended, others compressed and folded.
3. Cytoplasmic viscosity determined by MCHC (mean cell hemoglobin concentration, as MCHC rises, viscosity rises exponentially.

Question 28

What are the globin components of HbA, HbA2, and HbF, and what are their proportions?

Answer 28

HbA: • α2β2 ,96-98 %
Hb A2: • α2δ2, 1.5-3.2 %
HbF:• a2γ2
0.5-0.8 %

Question 29

Describe the structure of haemoglobin(2)

Answer 29

• Hb is a tetramer of 4 globin (α2β2) chains each with own haem gp.

2. Haem consists of protoporphyrin ring with Ferrous iron atom.

Question 30

What is the difference between alpha and beta chain length?

Answer 30

• Alpha chain is 141 amino acids long; Beta chain is 146 amino acids

Question 31

What is metabolism energy required for?(4)

Answer 31

 Maintenance of cation pumps
 Maintenance of RBC integrity and deformability
 Maintenance of Hb in reduced state
 Maintenance of reduced sulfhydryl groups in Hb and other proteins

Question 32

What are the key metabolic pathways of RBCs?

Answer 32

1. Glycolytic or Embden-Meyerhof Pathway
2. Hexose Monophosphate Shunt
3. Methaemoglobin reductase Pathway
4. Luebering-Rapoport shunt

Question 33

Describe the glycolytic pathway of RBCs(3)

Answer 33

 Glucose is metabolized and generates two molecules of ATP (energy).

 Generates 90- 95% of energy needed by RBC’s

 Functions in the maintenance of RBC shape, flexibility and the cation pumps

Question 34

Describe the pentose pathway of RBCs(3)

Answer 34

 The pentose phosphate shunt provides the reducing power, NADPH

 NADPH maintains glutathione in the reduced form (GSH)

 RBC uses GSH to protect it from oxidative damage

Question 35

Describe the methemoglobin reductase pathway for RBCs

Answer 35

 Maintains iron in the ferrous (Fe++) state.

 In the absence of this enzyme, methaemoglobin accumulates and it cannot carry oxygen

Question 36

Describe the Lueberg-Rapoport shunt

Answer 36

 Permits the accumulation of 2,3-DPG which is essential for maintaining normal oxygen tension, regulating haemoglobin affinity

2. Luebering-Rapoport pathway is a biochemical pathway in mature erythrocytes involving the formation of 2,3-bisphosphoglycerate and which regulates oxygen release from haemoglobin and delivery to tissues.
   2

Question 37

how does membrane cholesterol exist within a RBC?

Answer 37

→Membrane cholesterol exists in free equilibrium with plasma cholesterol.

Question 38

what determines the strength and flexibility of RBCs?

Answer 38

→ interactions between the membrane & cytoskeletal proteins

Question 39

what maintains surface area in the RBC?

Answer 39

→ strong cohesion between bilayer and membrane skeleton