10.08.18 Hemoglobin and Myoglobin

Question 1

Where does Hb bind O2?

Answer 1

Alveoli

Question 2

How does Hb assist in maintaining acid-base balance in the body?

Answer 2

By binding CO2 from metabolism and releasing CO2 when Hb reaches the lungs

Question 3

What is the bind O2/acid balance function of Hb dependent on?

Answer 3

partial pressure gradients of O2 or CO2

Question 4

Synthesized inside muscle cells and stores oxygen there for use at times of high metabolic demand

Answer 4

Myoglobin

Question 5

How does myoglobin content vary with skeletal muscle fiber type?

Answer 5

IA > IIA> IIB

Question 6

• Single polypeptide chain
• 80% alpha helical
• closely packed tertiary structure
  Single heme molecule covalently bound
• Binds on O2 molecule at heme

Answer 6

Myoglobin

Question 7

• 4 polypeptide chains (2 alpha, 2 beta)
• folds similar to myoglobin
• heme molecule covalently bound to each subunit- binds 4 O2
• Strong hydrophobic interaction between alpha and beta 1 and alpha and beta 2
• Weak polar interaction between a1b1 and a2b2

Answer 7

Hemoglobin

Question 8

97-98.5% of total Hb in adults; glycosylation is marker for chronically elevated blood sugar

Answer 8

HbA (a2b2)

Question 9

1.5-3% of total Hb in adult

Answer 9

HbA2 (a2delta2)

Question 10

Fetal Hb, major Hb from ~1 month gestation until near birth; ~40% at birth

Answer 10

HbF (a2gamma2)

Question 11

embryonic Hb, ~1 week post-conception until birth

Answer 11

HbE (zeta2epsilon2; a2e2; z2g2)

Question 12

imbalance in globin chain synthesis; can be due to gene deletion, mutations that affect gene regulation or splicing

Answer 12

Thalassemias

Question 13

What gene is dysregulated for beta-thalassemia minor

Answer 13

1 beta

Question 14

what gene is dysregulated for beta-thalassemia major (excess alpha chains, do not form tetramer)

Answer 14

2 betas

Question 15

what gene deletion usually has no symptoms?

Answer 15

1 alpha

Question 16

what gene deletion results in alpha-thalassemia trait

Answer 16

2 alphas

Question 17

What gene deletion results in HbH disease (names after beta4 tetramer formed here)

Answer 17

3 alphas

Question 18

What gene deletion results in Hb Bart’s disease or hydrops fetalis (Hb Bart’s is gamma4 tetramer)

Answer 18

4 alphas

Question 19

Fe-protoporphyrin IX

Answer 19

heme

Question 20

rings that form coordinate covalent bonds to Fe2+

Answer 20

Pyrrole rings

Question 21

the chains from the pyrrole rings interact with the surrounding alpha/beta globin chains to stabilize heme binding

Answer 21

hydrophobic

Question 22

What color is cyanocobalamin (Vit B12)

Answer 22

Pink

Question 23

mutations of the heme biosynthesis pathway

Answer 23

Porphyrias

Question 24

binding curve is hyperbolic, indicating a single constant affinity for O2

binding curve is sigmoidal, indicating changing affinity for O2 over the binding curve

Answer 24

Myoglobin

Hemoglobin

Question 25

partial pressure of O2 at which 50% of O2 binding sites are occupied

Answer 25

P50

Question 26

What does the taut conformation favor and what does the relaxed conformation favor?

Answer 26

Deoxy- T Oxy- R

Question 27

Produced in RBCs when glucose is abundant; binding allows Hb-bound O2 to dissociate and to supply O2 to tissues operating at a high metabolic rate; makes O2 release and is responsive to hypoxia allowing release at low pO2

Answer 27

2,3 DPG

Question 28

What physiological changes causes 2,3 DPG levels to change?

Answer 28

1. Chronic Obstructive Pumonary Emphysema 2. High Altitude 3. Chronic Anemia 4. Pregnancy

Question 29

In the lungs, high PO2 drives binding of O2 to Hb, release of H+ and formation of H2CO3. CA equilibrium favors synth of CO2 and H2O

Answer 29

Haldane effect

Question 30

In RBCs, protons bind to Hb and favor the T state, favoring O2 release

Answer 30

Bohr effect

Question 31

How does increase/decrease in pH affect O2 binding?

Answer 31

Increase favors O2 binding Decrease favors O2 release

Question 32

has a different beta chain and has a higher affinity for oxygen than adult hemoglobin; binds 2,3 DPG poorly

Answer 32

HbF

Question 33

Most common Hb variant

Answer 33

beta s variant

Question 34

What is the mutation in the beta s variant?

Answer 34

Glu6 changes to Val6

Question 35

What does HbA competitively bind to and why do they inhibit oxygen binding?

Answer 35

1. Cyanide 2. Carbon monoxide 3. Nitrogen dioxide 4. Hydrogen sulfide Don't change oxidation status of iron from Fe2+ to Fe3+ (results in O2 release)

Question 36

Mutations in any of the 3 AA on the distal side of the heme; characterized by cyanosis and brown color to blood

Answer 36

Hereditary Methemoglobinemia

Question 37

What are some other causes of methemoglobinema?

Answer 37

1. Mutations in PPP (G6PDH deficiency) because glytathione normally reduces ROS and prevents methemoglobin formation 2. Mutation in cytochrome b5 reductase (uses NADH from glycolysis to reduce Fe3+ in methemoglobin to Fe2+ and reversing formation of Fe3+)