Question

There are several naturally occurring mutations in Hb. Some of the mutations are benign (harmless) while others cause serious health problems for the individuals who carry them. The table below lists two different Hb variants and the observed effects of the amino acid substitutions. Use this table and the illustration of the heme binding site to answer the questions that follow for one of the different Hb variants below. Mutation Name Mutation Consequence Hb Hammersmith F42 in B subunits Hb Bristol V67D in B subunits The heme group is easily dislodged from its hydrophobic binding pocket. The protein is destabilized (and ultimately causes premature lysis of erythrocytes (hemolytic anemia)]

Answer 1

Answering for Hb bristol variant

Due to amino acid substitutions there are structural as well as functional changes . These include changes in size , shape , orientation, conformation, charge , hydrophobicity, changes in functional groups .

Due to the above said changes , the conformation, orientation and charge of the new amino acid may cause ineffective binding of the heme group at the hydrophobic binding pocket causing it to dislodge .

The changes lead to a defective hemoglobin which is not effective in binding O2 . This leads to sickle cell anemia which is one of the causes for hemolytic anemia

Defective Hb won't bind effectively to O2 in areas where O2 levels are poor , like mountain peaks. Heavy exercises, activities and outdoor sports would also take a toll on the health of that individual. Deformed Hb would cause the deformities in RBC shapes , leading to ineffective blood flow .