Haemoglobin Structure & Function Flashcards
When does globin synthesis begin?
Globin synthesis starts from the third week of gestation (prenatal) in the yolk sac
What does a decrease in O2 affinity cause?
Causes oxygen release
What is the result of high oxygen affinity?
Increased O2 affinity
=> Hb has highr O2 affinity
=> binds more strongly
What does a normal Hb curve depened on
[2,3-DPG]
[H+] (pH)
CO2 in RBC
Hb structure
How are different forms of Hb formed?
Various types of globin combine with haem to form the different haemoglobin
8 functional globin chains arrange in 2 clusters (A and B)
Describe the Bohr effect on oxyhaemoglobin curves
- An increase in CO2 production by tissues
- CO2 released into blood
- Dissociation curve shifts to right
- Release of O2 from Hb diffuses into tissues
- lower O2 affinity = unloaded readily
Describe the structure of Hb
- Globin chains have 4 polypeptide subunits (tetramers)
- 2 α globin chains
- 2 β globin chains
Each globin chain contains its own haem
What does a Bohr curve shifted to the right indicate?
Shift right = low affinity for O2
e.g.
Anemia, acedosis
despite less RBCs, they act more efficiently to deliver o2 to their target tissues
Outline the steps of O2 binding and unloading
- β chains slide over each other
- When oxygenated the globin chains move closer
- Deoxygenated globin chains pulled apart for 2,3-DPG -
decreasing affinity
Outline the significance of Globin?
In polyribosomes
- depends on genes
- precise order of amino acids in globin chains determines the function of Hb
What are the factors determining how much O2 binds to Hb?
- PO2
- PCO2
- Hb affinity for O2
What is oxygen affinity?
Ease with which haemoglobin binds and releases oxygen
Determines proportion of O2 released to tissues or loaded onto cells at a given oxygen pressure
What is indicated by a Bohr curve shifted to the left?
Left shift = high O2 affinity
e.g.
Presence of abnormal Hb, alkalosis
Hb less readily unloads O2 to tissues, binds strongly
What is the consequence of mutations on haemoglobin?
Deletions/mutations may lead to
- abnormal globin synthesis (sickle cell)
- Reduced rate of globin synthesis (thalassemia)
What is the relationship between 2,3-DPG and Oxygen delivery?
Increased 2,3-DPG causes more oxygen delivery to tissues
This is the body’s main response to hypoxia
What are the functions of Hb?
Carry O2 from lungs to tissues
- Remove CO2
- Buffer (maintains blood pH as it changes from oxyhaemoglobin to deoxyhaemoglobin
How is Haem synthesised?
In mitochondria
1. Iron supplied to reticulocyte by transferrin enzyme
2. Protoporphyrins (RBC precursors) synthesised (via EPO
and Vit. B12 regulation)
3. Protoporphyrin + Iron => Haem
How is CO2 transported in the body?
There are 3 mechanisms for CO2 transport
- Dissolution in plasma
- Formation of Carbonic acid
- Binding to carbaminohaemoglobin
What is 2,3-DPG?
2,3-diphosphoglycerate is a metabolite formed in red blood cells
controls the movement of oxygen from RBCs to tissues
How is Hb production regulated?
Regulation stimulated by hypoxia
Causes kidneys to produce more EPO, increasing RBC and Hb production
How does Hb transport oxygen?
1 Hb can bind to 4 oxygen in <0.01s
When oxygenated 2,3-DPG pushed out
β chains move closer together
How is Oxygen unloaded to tissues?
β chains pulled apart
2,3-DPG can enter between chains
results in lower O2 affinity
(this is responsible for the sigmoidal shape of oxygen dissociation curves)
What is the normal [Hb] in blood?
Adult male: 13.5-16.5g/dl
Adult femaile: 12.5-15.0g/dl
Which red cell precursors does Hb synthesis occur in?
65% in erythroblasts
35% in reticulocytes
How are the components of Haemoglobin synthesised in accordance to one another to produce sufficient Hb?
Haem and globin synthesis occur separately in developing red cell precursors
Synthesis rates are carefully coordinated to ensure optimal efficiency of Hb assembly
