haemoglobin Flashcards
98% of the cytoplasmic protein is
Haemoglobin
what type of protein is Haemoglobin
metalloprotein
what is the structure of haemoglobin
heterodimeric tetramer
2 beta chains 2 alpha chains
iron is chelated into protoporphyrin IX by
ferrochelatase to form the final molecule haem
ferrochelast incorporates iron into ….
haem subunits
Haem is located towards the
periphery of the globin chains
Haemogloobin binds oxygen via
Fe 2+
haemoglobin transports nitric oxide
via thiol groups
Transports CO2 =
carbaminohaemoglobin
when oxygen dissocation curve moved to right
affinity is decreased
2,3 is the major regulator of
02 affinity
2.3 is the intermediate product of
glycolysis
2,3DPG binds to
deoxyhaemoglobin in a 1:1 ratio
2,3 DPG stabilises ….
the quaternary structure of Hb via -chains
2.3 DPG Changes Hb from an R state
to T state
2,3DPG is released at high …
po2
The bohr effect is
The effect of pH on Hb-oxygen affinity
Is HB and impornant buffer
yes
Proton accepted when
oxygen released
Lactic acid and CO2 increase
[H+]
Raised [H+] causes reduced oxygen affinity for Hb, releasing more
oxygen to tissues
Two α and β chains form dimers through
low energy non-covalent bonds
Low energy bonds promote specific 3D structure comprising
A-H α helices
Non-α-helical segments
what does f8 (proximal histidine ))
binds iron)
E7 distal histidine binds
oxygen
So what happens to the proximal F8 histidine
In its resting state the ferrous iron is out of plane with the F8 histidine – approx 8° or 0.4-0.6A.
Binding of oxygen alters the structure of the haem moiety.
Haem reorientation leads to the movement of iron into the plane of the F8 histidine.
Breakage of hydrogen bonds leads to conformational modification.
the folded chains place iron near the exterior so
readily accessible to oxygen
Each subunit contains a haem
moiety
At the centre of the haem moiety is
iron
E7 Histidine binds oxygen in
oxyhaemoglobin
Hydrophobic pocket protects Fe2+ from
oxidation.
Chromosome 16 =
α-like gene cluster
Chromosome 11
β-like gene cluster
Main adult haemoglobin HbA is most efficient at carrying
oxygen
Alterations in globin chain expression can be associated with
disease
Carboxyhaemoglobin
Hb plus carbon monoxide affinity is 281x greater than
oxygen
Carboxyhaemoglobin does not bind
oxygen
traits of methaemoglobin
Fe3+ Cannot bind oxygen Usually formed during glycolysis Can be inherited or acquired RR 0.2-0.6% Inherited with: cytochrome b5 reductase deficiency and Haemoglobin M
Low levels of CO have major impact on
haemoglobin function
Haemoglobinopathies
quantitative defect
Reduced synthesis of normal globin chains
Thalassaemias
Haemoglobinopathies
qualitative defect
Structural variants HbS HbC HbD Hbe
Thalassaemia describes conditions involving
globin chain imbalance