L2 Haemoglobin, related disorders

characteristics of erythrocyte

• simple - no nucleus, ribosomes, mitochondria

• unattractive to infecting organisms

• no protection

• no capacity for mRNA or new protein translation

• limited reducing power or capacity to generate ATP so vulnerable to damage

what forms the membrane skeleton and the horizontal lattice of the cytoskeleton

• spectrin

• ankyrin

• protein 4.2

• actin

what is the most abundant protein found within the erythrocyte membrane

spectrin

local damage

• fibrin strands in circulation caused by local clotting activation

• slicing damage

• vacuole pops but red cell is sealed

• cytoskeleton structure allows self repair

diffuse damage

• inherited abnormal cytoskeleton or heat, toxins, antibodies may cause diffuse membrane loss

• small sealed blebs of membrane are lost 

• cell shrinks becoming rigid sphere

• spherocyte formed and removed by spleen

inherited abnormal cytoskeleton

• loss of anchoring proteins in membrane

• hereditary spherocytosis - defect of red cell membran edprotein such as ankyrin or band 3

what leads to spleen enlargement

• red cell membrane is unstable, lost

• spherocytes formed (diffuse damage)

• rapid breakdown of RBC cause anaemia (<30 days turnover)

• breakdown products of RBC leads to mild jaundice and gall stones, inc bile

• inc rbc destruction leads to spleen being enlarged

haemoglobin in circulation

• through diffuse damage

• highly toxic

• cytoskeleton repair helps to prevent this leakage

porphyrin structure

• holds iron in flat 2D structure

• 2 interaction sites above and below the plane

  • one fix molecule to globin

  • one for oxygen

interconnection of chains of haemoglobin

• after release of first oxygen structure becomes tighter

• more likely to release another oxygen as tight formation has less room

what else influences tight or loose conformation of haemoglobin

• pH

• CO2

• metabolic products

why does foetal haemoglobin have higher affinity for oxyegn

• doe snot bind to 2,3 DPG

G6PD glucose 6-phosphate dehydrogenase

• red cell enzyme that generates reducing power NADPH that protects haemoglobin from oxidative damage 

G6PD deficiency

• oxidative stress is high, Hb is damaged, RBC destroyed

• prevalent gene in Africa, Arab states

• cause death after some medicines which inc oxidation and cause chronic anaemia

how does G6PD deficiency lead to anaemia

• pentose phosphate cannot function

• reducing power NADPH is not generated

• H is damaged

• shrinks to one cell in denatured form

• anaemia

how is G6PD deficiency an advantage 

• cells infected by malaria are inhospitable

• less available for the parasite to be consumed