L22- Types of Hb Flashcards
how many different types of Hb
3
name the types of Hb
HbA
HbA2
HbF
HbA
major adult Hb
- Composed of:
o 2 alpha chains
o 2 B chains
HbA2
minor adult Hb
- Composed of:
o 2 a chains
o 2 𝛿 chains
HbF
the normal faetal Hb
- Composed of:
o 2 alpha (a) chains
o 2 gamma (Y) chains
features of HbF
o Has a greater affinity for oxygen than HbA so ensures oxygen transfer from maternal ciruclation to fetus RBCs through placenta
o Has a lower affinity for BPG
HbA1C
(glycosylation of HbA)- has glucose residues attached to B-globin chains
- used to monitor diabetes
expression of different alpha and beta globing genes is
regulated during development
i.e. alpha chains exist during foetal development, but beta chains only start being expressed near the end of pregnancy
where are alpha-globin -like genes located
chromosome 16
where are beta- globin- like genes located
chromosome 11
haemoglobin are formed by
combination of alpha globing like genes and B-globin like chains
structure of Hb
4 polypeptide chains
- quaternary
- 2 x alpha
- 2 x beta
important of foetal Hb
- HbF is the major Hb in foetal blood
- Higher binding affinity for oxygen than HbA which allows transfer of oxygen to foetal blood supply from the mother
sickle cell anaemia is causes by
mutation of glutamate to valine in Beta globin
mutation of glutamate to valine in Beta globin causes
HbS- Hb sickle
valine causes
sticky hydrophobic pockets to form- allows deoxygenated HbS to polymerase
HbS polymerisation caused by hydrophobic pockets formed by valine
- tetrameric Hb stick together forming chains
- long chains of Hb cause the sickle shape
dangers of sickle cell (2)
- Sickle cells are more prone to lyse (anaemia)
- More rigid (block microvasculature)
thalassaemia
Group of genetic disorders where there is an imbalance between the number of alpha and Beta globin chains
B- thalassaemia
- Decreased or absent B-globin chain production
- Alpha chains unable to form stable tetramers
- Symptoms appear after birth
If you lose 1 B-globin copy on chromsosmes 11
Minor
If you lose both B-globin copy on chromsosmes 11- Major
major
alpha-thalassaemia
- Decreased or absent alpha-globin chain production
- Several diff levels of severity due to multiple copies of the alpha chain present
- B-chains can form stable tetramers with increased affinity for oxygen
- Onset before birth
adults haemoglobin has
4 haem-containing subunits, 2alpha and 2 B chains of which can bind a molecule of O2
Haemoglobin can exists in 2 interchangeable states:
o Low affinity T state (high affinity)
o High affinity R state (low affinity)
Binding of oxygen to one subunit of haemoglobin causes
conformational changes which promotes the R state
Sigmoidal binding curve for oxygen binding to haemoglobin is physiologically important as it
allows for efficient oxygen binding and delivery
Oxygen binding to haemoglobin is dependent
on [CO2, H+ and BPG]
o These effectors work by stabilising the T state
what inhibit Hb
CO
