haemoglobin structure and function

Question 1

what is the primary structure of globin

Answer 1

alpha chain has 141 amino acids
beta delta and gamma have 146 amino acids

Question 2

what is the secondary structure of globin

Answer 2

70% of alpha helix

Question 3

what is the tertiary structure of globin

Answer 3

facing of inward non polar residues determines folding

Question 4

what is the quartenary structure of globin

Answer 4

tetrameric, 2 dimers (1 is alpha 1 is beta on top of 2 which is alpha 2, beta ) structure changes on oxygenation allosteric effect

Question 5

what is the haem structure
what kind of ring with an iron atom at centre

Answer 5

protoporphyrin ring

Question 6

in the haem structure of haemoglobin how many covalent links to nitrogen of pyrrole rings

Answer 6

4 covalent links to nitrogen or pyrrole rings

Question 7

in haem structure how many covalent links to histidine in globin

Answer 7

2 covalent links to histidine in globin

Question 8

why is the distal histidine bond unstable (haem structure)

Answer 8

replaced by oxygen co-operative bond) to form oxy-hb

Question 9

why is h+ and co2 bind to haem

Answer 9

to promote o2 release. bohr effect

Question 10

what does increasing dpg do to haemoglobins affinity for oxygen

Answer 10

decreases

Question 11

how is haem synthesised

Answer 11

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

Question 12

how is globin synthesised

Answer 12

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

Question 13

how many introns and exons do globin genes have

Answer 13

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

Question 14

when is alpha globin produced

Answer 14

during early pregnancy

Question 15

when is beta globin produced

Answer 15

near time of birth

Question 16

what type of globin is not produced after birth

Answer 16

gamma globin

Question 17

when is dpg release increased

Answer 17

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

Question 18

what is the bohr effect and how does it change the oxygen dissociation curve

Answer 18

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.

Question 19

what are two examples of haemoglobin disorders

Answer 19

sickle cell anaemia
beta thalassemia

Question 20

what is the physiology of thalassaemia

Answer 20

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

Question 21

thalassaemia therapy

Answer 21

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

Question 22

sickle cell anaemia

Answer 22

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

Question 23

what are the clinical features of sickle cell anaemia

Answer 23

sudden dumping of red cells (sequestrian crises)
spleen infarction

Question 24

what are clinical features of beta thalassaemia

Answer 24

iron overload
bone marrow expansion

Question 25

what are the complications of sickle cell anaemia

Answer 25

-bacteremia
-vaso-occlusion pain
chest syndrome
stroke
chronic organ damage
sickle hand foot syndrome

Question 26

what is the management of sickle cell anaemia

Answer 26

prevent and treat acute complications
prevent organ damage
specific anti sickling options transfusion
curative stem cell transplantation or gene therapy

Question 27

how does sickle cell anaemia affect the blood, marrow, spleen, skin, bone , kidney, eye

Answer 27

blood- haemolytic anaemia
-marrow- marrow hyperplasia
spleen- hyposplenism
-skin- chronic leg ulcer
bone- avascular hip necrosis osteomyelitis
kidney- chronic renal failure
eye- prolif retinopathy, retinal detachment

Question 28

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