Globin/sickle cell

Question 0

T vs R state?

Fe/Heme plane for each?

Answer 0

T- low affinity (Fe above heme plane)

R- high affinity (Fe in plane)

Question 1

Myoglobin structure

Answer 1

monomer; 1 heme; helical

Question 2

Hemoglobin A2B2 inter-domain strengths

Answer 2

A1B1=A2B2 > A1A2> A1B2=A2B1 > B1B2

Question 3

T–>R Domain movements

Answer 3

R: A——–A, B-B
T: A-A, B——–B

Question 4

What is Hill coefficient?

Answer 4

Describes cooperativity (higher # = higher cooperativity)

Question 5

What does allosteric inhibitor do?

Answer 5

Stabilize T (deoxy)
Shifts binding curve RIGHT

Question 6

What are 3 allosteric inhibitors?

Answer 6

1. pH (bohr effect) - T has greater affinity for H+ (exercise)
2. 2,3 BPG - bind between beta subunits (high altitude)
3. CO2 binding (carbamoylation)- (exercise)

Question 7

What is wrong with stored blood?

Answer 7

Decreased BPG –> will not unbind O2 –> treat with inosine

Question 8

Name the different forms of hemoglobin (5) and subunits of each

Answer 8

HbA- 		A2B2
HbA2- 		A2D2
HbF- 		A2G2
Embryonic	A2E2
PreEmbryonic	Z2E2

Question 9

Production of each globin subunit: gestation –> birth (ABG)

Answer 9

Alpha- consistent
Beta- Increase prior to birth
Gamma- Decreases prior to birth

Question 10

Alpha chain chromosome?

Answer 10

16 (4 genes)

Question 11

Beta chain chromsome?

Answer 11

11 (2 genes)

Question 12

What is the point mutation of HbS?

what happens to the protein?

Answer 12

• glu6val (beta globin gene)

- protein is functional, but causes sickling

Question 13

Describe HbE diseases

Where is it common?

Answer 13

beta globin variant; common in SE Asia

• HbSE - Sickle cell anemia
• HbEE - low severity chronic anemia

Question 14

Describe HbC disease.

Where is it common?

Answer 14

Beta globin variant; W Africa

• HbSC - sickle cell anemia
• HbCCC - chronic anemia

Question 15

Describe HbD diseases.

Where is it common?

Answer 15

Beta globin variant; varies by geography; Middle E, India

• HbSD- mild SCA; vasoocclusion; premature RBC breakdown
• HbDD- mild anemia, occasional splenomagaly

Question 16

What is the normal HbA2 level?
What does elevated HbA2 level indicate?
Low level?

Answer 16

• 3.5%
• high level: beta thalassemia
• low level: alpha thalassemia

Question 17

Types of beta thalassemia?

Answer 17

Trait
Homozygous beta +
Homozygous beta 0

Question 18

MCV? normal?

Answer 18

Mean corpuscular volume 80FL

Question 19

What are the gene mutations that cause alpha thalassemia? Frequency of each?

Answer 19

90% gene deletions (cis and trans)

10% Constant Spring (missense–> elongation)

Question 20

You have to rule out Fe deficiency for what disease?

Answer 20

Alpha thalassemia trait/minor

Question 21

Alpha thalassemia carrier vs trait/minor

Answer 21

Carrier- single gene deletion (silent)

Trait/minor- 2 gene deletions (cis or trans)

Question 22

Name the alpha thalassemias and genetics of each

Answer 22

• HbH: cis + silent carrier
• HbH+constant spring: cis + CS
• Hb Barts Hydrops Fetalis (cis+cis)

Question 23

Sickle cell disease screen and diagnosis

Answer 23

Screen: isoelectric focusing (IEF)
Diagnose: CBC, Hb electrophoresis