Erythrocyte Metabolism, Membrane Structure and Function

Question 1

What is the general structure of hemoglobin ?

Answer 1

• cytoplasm of RBC contains abundant hemoglobin
  
  • complex of portoporphyrin, iron, and globins
• composition of hemoglobin
  
  • 4 globin chains
  • each chain contains iron in the Ferrous state
    
    • allows each hemoglobin molecule to carry 4 O2 molecules

Question 2

After the RBC enters peripheral circulation and

loses its nucleus, how does it make energy ?

Answer 2

• generates ATP via anaerobic glycolysis
  
  • the ATP generated helps prevent the oxidation of the iron and maintains the RBC membrane integrity
  • limits the RBC lifespan to 120 days
  • after that everything gets recycled
    
    • except for protoporphyrin (cant be re-used)
      
      • excreted in bilirubin

Question 3

Why do RBC s rely on anaerobic glycolysis ?

Answer 3

• they lack mitochondria
• most cellular processes occurring in the RBC require energy
  
  • except for the exchange of O2 and CO2
    
    • this occurs because the oxygen and or CO2 flow from high to low partial pressure
• requires glucose for energy production (get it from plasma)
  
  • enters via GLUT1 receptor

Question 4

What is the term for all the disorders of RBC

that occur due to enzyme issues of the anaerobic glycolysis pathway ?

Answer 4

• hereditary nonspherocytic hemolytic anemia

Question 5

How much ATP is generated by anaerobic glycolysis ?

Question 6

What are the three shunt pathways

off the anaerobic glycolytic pathway ?

Answer 6

• hexose monophosphate
• methemoglobin reductase pathway
• rapoport-luebering pathway

Question 7

What pathway is G6PD part of and why

is it so important to RBC metabolism ?

Answer 7

• G6 PD is part of hexose monophosphate pathway
• it is the only way to generate NADPH for glutathione reduction
• in its absence RBCs are particularly vulnerable to oxidative damage
  
  • G6PD deficiency
    
    • most common inherited RBC enzyme deficiency worldwide
    • ability to detoxify is hampered
    • leads to a hemolytic anemia

Question 8

When is hemoglobin, methemoglobin ?

Answer 8

• methemoglobin is when iron is in the Ferric state (3+) and cannot bind oxygen
• hemoglobin is constantly exposed to oxygen and peroxide
• IMP:
  
  • hexose mannose phosphate pathway prevents oxidation of hemoglobin by reducing peroxide
  • but once methemoglobin is formed HMP can’t get rid of it

Question 9

What shunt pathway is 2,3 BPG part of and what is

it’s role in oxygen delivery ?

Answer 9

• part of Rapoport Luebering pathway (shunt pathway)
• 2,3 BPG
  
  • binds between the globin chains in the interior cavity of the hemoglobin tetramer
  • stabilizes it in the deoxygenated state
  • shifts the O2 dissociation curve to the right (enahnces O2 delivery to tissues)

Question 10

What is the cell deficient of in PNH

and what gene is involved ?

Answer 10

• PIGA gene is involved and is key to the production of the phosphotidyl inosital anchor (GPI)
  
  • the cell membrane becomes deficient in CD55 and CD59
  • susceptible to complement mediated lysis
• this is an acquired mutation

Question 11

Review figures p. 85-87

Question 12

Band 3 and protein 4.2 are involved in the

cytoskeleton how ?

Answer 12

• major components of the ankryin complex
• they link their associated proteins and lipid bilayer membrane to the spectrin cytoskeleton via ankryn

Question 13

What proteins are important in the ankryn

junctional (4.1) complex ?

Answer 13

• band 3, protein 4.2, adducin and actin are all part of this complex
• they link the lipid membrane to the spectrin cytoskeleton through protein 4.1

Question 14

Spectrin gives what type of stability to the RBC membrane ?

Answer 14

• alpha and beta spectrin combine and are not part of /do not cross the lipid bilayer
• they provide lateral or horizontal membrane stability
• also called peripheral proteins

Question 15

Ankryin gives what type of stability to the

RBC membrane ?

Answer 15

• vertical

Question 16

What defects lead to Hereditary Eliptocytosis?

Answer 16

• several autosomal dominant mutations
• affect spectrin (lateral bonds) or spectrin to protein 4.1 junction
• horizontal membrane defects lead to progressive elongation of the RBC membrane
• can cause a mild to severe hemolytic anemia

Question 17

What are the defects seen in Hereditary Spherocytosis ?

Answer 17

• also autosomal dominant mutations
• band 3
• ankryn
• protein 4.2
• or spectrin interactions
• loss of vertical anchorage leads to the spherocyte formation
  
  • reduced surface area

Question 18

Defects in what other protein

have been linked to hereditar spherocytosis ?

Answer 18

• Aquaporin 1