haemoglobin structure and function Flashcards
what is the primary structure of globin
alpha chain has 141 amino acids
beta delta and gamma have 146 amino acids
what is the secondary structure of globin
70% of alpha helix
what is the tertiary structure of globin
facing of inward non polar residues determines folding
what is the quartenary structure of globin
tetrameric, 2 dimers (1 is alpha 1 is beta on top of 2 which is alpha 2, beta ) structure changes on oxygenation allosteric effect
what is the haem structure
what kind of ring with an iron atom at centre
protoporphyrin ring
in the haem structure of haemoglobin how many covalent links to nitrogen of pyrrole rings
4 covalent links to nitrogen or pyrrole rings
in haem structure how many covalent links to histidine in globin
2 covalent links to histidine in globin
why is the distal histidine bond unstable (haem structure)
replaced by oxygen co-operative bond) to form oxy-hb
why is h+ and co2 bind to haem
to promote o2 release. bohr effect
what does increasing dpg do to haemoglobins affinity for oxygen
decreases
how is haem synthesised
in red cell precursors mitochondria and cytoplasm
enzyme controlled steps-
glycine and succinate condense to form d-ala delta amino laevulinic acid
porphoblinogen
iron inserts into proto-porphyrin
rate controlling steps
ALA synthase, iron increases rate, haem inhibits
how is globin synthesised
globin genes on chromosome 11 and 16
on chromsome 11 fetal gamma2 is alpha 2 on chromosome 16
on chromosome 11 a2 delta 2 is alpha 2 on chromosome 16
on chromosome 11 gene A beta2 is alpha 2 on chromosome 16
how many introns and exons do globin genes have
3 exons and 2 introns
splicing machinery recognise sequences then introns removed from transcribed mrna 5’ end of mrna capped so it can attach to ribosomes
3’ end is poly adenylated to stabilise
when is alpha globin produced
during early pregnancy
when is beta globin produced
near time of birth
what type of globin is not produced after birth
gamma globin
when is dpg release increased
in response to anaemia, hypoxia
right shift of oxygen dissociation curve so effective oxygen delivery higher p50
sigmoidal shape of curve- changes in po2 at higher levels have little effect on o2 saturation
bohr effect- pco2 increases and ph lowers and so reduction in ph shifts curve to right
what is the bohr effect and how does it change the oxygen dissociation curve
the bohr effect is when the carbon dioxide increases and so the ph is lowered, lowering the affinity of haemoglobin for oxygen and so curve shifts to the right.
what are two examples of haemoglobin disorders
sickle cell anaemia
beta thalassemia
what is the physiology of thalassaemia
reduced production of alpha or beta globin
leads to globin imbalance and precipitation
results in haemolysis in red cells
ineffective erythropoiesis
alpha thalassaemia: 0= deletion of both alpha genes
+= deletion of 1 alpha gene
beta thalassaemia- many non deletional mutations #0 mutations severe so no beta globin synthesis for that allele
+mutations milder so some beta globin synthesis
thalassaemia therapy
standard therapy
transfuse for 3-4 weeks
chelate- desferrioxamine
monitor- serum ferritin liver iron conc, heart iron and function organ damage
bone marrow transplantation
gene therapy replacement or beta to gamma switching
sickle cell anaemia
autosomal recessive
deoxy haemoglobin forms crystals
heterozygotes have 50% healthy haemoglobin
homozygotes have 100% sickled haemoglobin
vaso-occlusion microvascular obstruction acute crises
chronic progressive organ damage
hbs polymerisation at low po2 causes sickled erythrocytes
they block microcirculation
dynamic reversible process
what are the clinical features of sickle cell anaemia
sudden dumping of red cells (sequestrian crises)
spleen infarction
what are clinical features of beta thalassaemia
iron overload
bone marrow expansion
