Biochemistry Sickle cell anemia is a genetic blood disorder

Biochemistry: Sickle - cell anemia is a genetic blood disorder that results from a point mutation in hemoglobin. Hemoglobin is a protein made of four subunits: t wo alpha chains and two beta chains. A mutation in the gene for the beta subunit changes an E at amino acid position 6 to a V. This change causes the hemoglobin molecules to polymerize, forming fibers under low blood oxygen conditions.

a) Explain how a s ingle amino acid change can cause such a large effect on protein structure.

b ) Below is a graph of the binding curves for fetal hemoglobin and adult hemoglobin. Explain the major difference (s) between fetal and adult hemoglobin.

c) List two major differences between myoglobin and hemoglobin.

100 95.8 50 Fetal hemoglobin Adult hemoglobin 19 26.8 40 80 120 oxygen partial pressure Cpoe mmHg)

Solution

A) due to change in one amino acid the whole protein structure changes because as the amino acids changes the acidity or basicity of the protein molecules also changes due to which the folding of the secondary and tertiary structure also changes which depend on the nature and type of amino acids present in them..!! Due to which the type of intermolecular bonds also changes with the presence of different amino acids..!!

Hence due to which as in case of sickle cell also Glutamic acid is being replaced by valine i.e acidic amino acid to neutral hence its folding, shape also gets changed hence I causes a effect...

C) the first difference between the Hb and Myoglobin is in Hb 4 iron atoms binds with 1 oxygen molecule, whreares in Myoglobin 1 iron atom binds with 1 oxygen molecules..!!

Second difference comes for the binding affinity.. Myoglobin binds with the oxygen with higher affinity than Hb but it gets saturated very fast hence cannot transport more oxygen hence follows an curve graph, whereas in case of Hb it\'s binding affinity is little less than Myoglobin but can transport more oxygen than Myoglobin as it requires more partial pressure of oxygen concentration to gets saturated hence follows the Sigmoid graph as shown above...!!!

B) in case of adult Hb it is made up of 2 chains alpha and beta chains 2 each..!! In case of fetel Hb it is made also made up of 2 each chains (1) alpha chains and (2) gamma chains (replacement of beta chains in adult) . This gamma chains has more binding affinity for oxygen as compared to the beta chains of adult Hb hence binds with oxygen faster in less partial pressure of oxygen too which helps the fetus to provide more supply of oxygen...!!! As we see in the graph the fetus Hb reaches the same oxygen level even in less partial pressure of oxygen as compared to adults Hb...!!!