sickle cell anemia

Question 1

what type of protein is the normal haemoglobin (HbA) ?

Answer 1

• it is a quaternary protein, which is a tetramer composed of 2 ⍺-globin chains & ꞵ-globin chains

Question 2

are the ⍺ & ꞵ chains coded for by the same gene?

Answer 2

• NO!!

- they are coded for by 2 different genes found on 2 different chromosomes

Question 3

what mutation occurs in the gene coding for the ꞵ-globin chains?

Answer 3

• a single nucleotide substitution mutation

Question 4

what nucleotide is being replaced by what in the DNA template strand?

Answer 4

• the thymine nucleotide is replaced by the adenine nucleotide

Question 5

what happens as a result of the single nucleotide substitution mutation?

Answer 5

• the 6th codon in the mRNA is changed, resulting in the 6th amino acid of the chain being changed from glutamate to valine

Question 6

why does the change in the 6th codon from glutamate to valine result in the formation of a mutated haemoglobin molecule (HbS)?

Answer 6

• as the R group of glutamate is hydrophilic, while the R group of valine is hydrophobic, folding of the ꞵ-globin chains into its precise 3 dimensional conformation is now affected
• this results in the formation of a mutated haemoglobin molecule that has a hydrophobic region in the surface of the protein, due to valine, which is a hydrophobic amino acid residue

Question 7

what happens to the HbS haemoglobin molecules in low oxygen concentrations?

Answer 7

• the HbS haemoglobin will interact with each other via hydrophobic interactions, & crystallise into rod-shaped fibres

Question 8

what is a result of HbS haemoglobin crystallising to form rod-like fibres in low oxygen concentrations?

Answer 8

• HbS haemoglobin is less effective in carrying oxygen compared to HbA haemoglobin, resulting in anemia

Question 9

what does the rod-like fibres of HbS distort?

Answer 9

• the rod-like fibres of HbS distorts the normal circular, biconcave disc shape of the red blood cell into a sickle shape

Question 10

what happens as a result of red blood cells sickling?

Answer 10

• blood vessels are blocked

Question 11

what consequences arise due to the blocked blood vessels caused by red blood cells sickling?

Answer 11

• interference of blood circulation, which deprives organs of oxygen

Question 12

what happens as organs are deprived of oxygen?

Answer 12

• organs may become damaged & lead to death

Question 13

why would be one’s spleen be enlarged if they have sickle cell anemia?

Answer 13

• as sickle-shaped red blood cells have a shorter lifespan compared to normal red blood cells, more sickle-shaped red blood cells in a human affected with sickle cell anemia will be sent to the spleen in the same time period than normal red blood cells in a healthy human
• this results in an accumulation of sickle-shaped red-blood cells in the spleen

Question 14

what are some other side effects of sickle cell anemia?

Answer 14

• skull deformation
• enlargement & then fibrosis of the spleen
• abdominal pain
• rheumatism

Question 15

how does sickle-cell anemia cause skull deformation?

Answer 15

• as sickle-shaped red blood cells are rapidly destroyed, this leads to anemia
• anemia causes overactivity of the bone marrow, causing an increase in the amount of bone marrow, resulting in skull deformation

Question 16

how does sickle cell anemia result in abdominal pain & rheumatism?

Answer 16

• as red blood cells with HbS haemoglobin sickle in low oxygen concentrations, it can cause the sickle-shaped red blood cells to clump in blood vessels, interfering with blood circulation
• the interference of blood circulation can result in local failures in blood supply, resulting in gastrointestinal, as well as muscle & joint damage, causing abdominal pain & rheumatism respectively

Question 17

what are the 5 differences between HbA & HbS?

Answer 17

1. the gene on the template DNA strand coding for ꞵ-globin chain
2. resultant codon 6 on mRNA
3. resultant amino acid 6 on the polypeptide chain
4. solubility at low oxygen concentrations
5. appearance of red blood cell

Question 18

what is the difference between HbA & HbS in terms of the gene on the template DNA strand coding for ꞵ-globin chains?

Answer 18

• on HbA, the gene will be … CTC …

- while on HbS, the gene will be … CAC …

Question 19

what is the difference between HbA & HbS in terms of the resultant codon 6?

Answer 19

• on HbA, the resultant codon 6 is … GAG … ,

- while on HbS, the resultant codon 6 is … GUG …

Question 20

what is the difference between HbA & HbS in terms of the resultant amino acid residue 6 on the polypeptide chain?

Answer 20

• in HbA, the resultant amino acid residue 6 on the polypeptide chain is glutamate, which is hydrophilic
• while in HbS, the resultant amino acid residue 6 on the polypeptide chain is valine, which is hydrophobic

Question 21

what is the difference between HbA & HbS in terms of their solubility in low oxygen concentrations?

Answer 21

• in HbA, the haemoglobin remains soluble,

- whereas in HbS, the haemoglobin is insoluble, & crystallises into rod-like structures

Question 22

what is the difference between HbA & HbS in terms of their appearance?

Answer 22

• red blood cells with HbA haemoglobin are circular, biconcave disc-shaped
• while red blood cells with HbS haemoglobin are sickle-shaped