Hemoglobin Structure and Function Flashcards
What is haemoglobin?
Haemoglobin (Hb) is a globular hemoprotein made up of 1/3 of red blood cell
Hemoproteins are a group of specialised proteins that contain haem as a tightly bound prosthetic group
Haem is a complex of protoporphyrin IX and ferrous iron (Fe2+)
Iron held in the centre of haem molecule by bonds to the 4 nitrogen of a porphyrin ring
How is haemoglobin synthesised, what is the normal concentration?
65% of the Hb is synthesised in the erythroblasts, and 35% at the reticulocyte stage
Normal conc. Of Hb in blood:
Adult male- 13.5-16.5 g/dl
Adult female- 12.5-15.0 g/dl
Regulation:
Stimulated by tissue hypoxia
Hypoxia causes the kidneys to increase production of EPO which increases RBC and Hb production
Various types of globin combine with haem to form different haemoglobin
Eight functional globin chains, arranged in two clusters;
B-cluster (beta, gamma, delta and epsilon globin genes) short arm of chromosome 11
A-cluster (alpha and zeta globin genes) short arm of chromosome 16
How is haem synthesised?
Haem synthesis occurs largely in the mitochondria
Chain of events
Iron delivery & supply where iron is delivered to the reticulocyte by transferrin
Synthesis of protoporphyrin
Occurs in the mitochondria of RBC precursors
Mediated by EPO and vitamin B6
Protoporphyrin + iron=haem
How is globin synthesised?
Globin is a protein so synthesis occurs in the polyribosomes (RER)
Rates of haem and globin synthesis are carefully coordinated to ensure optimal efficiency of Hb assembly
Proper globin synthesis depends on genes
Precise order of amino acids in the globin chains is critical to the structure and function of haemoglobin
What are the main functions of haemoglobin?
Carry oxygen from the lungs to the tissues
Remove CO2
Buffering action, maintains blood pH as it changes from oxyhaemoglobin (carrying O2) to deoxyhaemoglobin (without O2)
How is oxygen delivered via haemoglobin?
Oxygen delivery to the tissues:
One Hb can bind to four O2 molecules
Less than 0.01 sec required for oxygenation
When oxygenated 2,3-DPG is pushed out; the beta-chains move closer
Beta-chains are pulled when O2 is unloaded, permitting entry of 2,3-DPG resulting in lower affinity of O2
The amount of O2 bound to haemoglobin and released to tissues depends on:
PO2 and
PCO2 but also the
Affinity of haemoglobin for O2
Oxygen affinity is the ease with which haemoglobin binds and releases oxygen
What is oxygen affinity?
Determines the proportion of O2 released to the tissues or loaded onto the cell at a given oxygen pressure
Increases in oxygen affinity mean haemoglobin has an increased affinity for O2, so it binds more & strongly
Decreases in oxygen affinity, cause O2 to be released
What is the Bohr Effect?
Alterations in blood pH, shifts oxygen dissociation curve
In acidic pH the curve shifts to the right resulting in an enhanced capacity to release O2 where it is needed
What are the different factors that affect the Hb-oxygen dissociation curve?
The normal position of curve depends on: Concentration of 2,3-DPG H+ ion concentration (pH) CO2 in red blood cells Structure of Hb Standard conditions: Temp= 37OC pH= 7.40 BE= 0
What are the three mechanisms of carbon dioxide transport?
Three mechanisms of transport
Dissolution in the plasma
Formation of carbonic acid
Binding to form carbaminohemoglobin
What are the haemoglobin derivatives?
Oxyhaemoglobin (oxyHb): Hb with O2
Deoxyhaemoglobin (DeoxyHb): Hb without O2
Methaemoglobin (metHb): contains Fe3+
Carboxyhemoglobin (HbCO)- CO binds to Fe2+ in haem in cases of CO poisoning
Carbaminohemoglobin (HbCO2): CO2 binds non-covalently to globin chain of Hb. HbCO2 transports CO2 in the blood (20%)
Why do globin disorders happen?
The genes for globin chains occur in clusters on chromosomes
11 (epsilon, gamma, delta and beta)
16 (zeta and alpha)
Expression of alpha and beta-globin closely balanced
Mutations or deletions may lead to:
Abnormal synthesis of globin chain as in Sickle Cell Diseases
Reduced rate of synthesis of normal globin chains as in thalassaemia
What is sickle cell disease?
Group of Hb disorders with inherited sickle beta-globin gene
Sickle cell anaemia (HbSS) homozygous, most common:
A substitution from GAG to GTG which produces valine instead of glutamic acid
What causes thalassaemia?
Beta-thalassaemia
Loss of 1 beta-chain causes mild microcytic anaemia (thalassaemia trait)
Loss of both ( b0) causes thalassaemia major
Excess alpha-chains precipitate in erythroblasts causing haemolysis and ineffective erythropoiesis
Alpha-thalassaemia
There can be loss of 1,2,3 or 4 alpha chain
