Myoglobin and Hemoglobin

Question 1

How long will you see embryonic Hb present?

Answer 1

~ 1 week post-conception until birth

Question 2

CO + heme in Hb (HbCO)=

Answer 2

Carboxyhemoglobin –>forms more readily than oxyhemoglobin (HbO2)

Question 3

What is the most common Hb variant associated with pathology in the US? What disease does it cause?

Answer 3

B^s mutation; sickle cell anemia

Question 4

Methemoglobinemia is characterized by

Answer 4

Chocolate blood and cyanosis

Question 5

What are 4 substances that competitively bind to the Fe-binding site in heme and which one binds up to 300x stronger than O2?

Answer 5

1. Cyanide (CN^-)
2. Carbon monoxide (CO)
3. Nitrogen dioxide (NO₂)
4. Hydrogen sulfide (H₂S)

CO binds very strongly to Hb

Question 6

Mutations in cytochrome b5 reductase cause hereditary ________. What is the purpose of this enzyme?

Answer 6

This enzyme uses NADH generated through glyceraldehyde phosphate dehydrogenase (glycolysis) to reduce Fe3+ in methemoglobin to Fe2+ thereby reversing formation of Fe3+.

Question 7

alpha2 delta2

Answer 7

HbA2

Question 8

2,3-DPG (same as 1,3-BPG) is present in all RBCs in adults and is produced in RBCs when _____ is abundant and stabilizes the __ state

Answer 8

glucose; T

Question 9

Most CO2 enters RBCs and 15 % of the time forms _____ _____with Hb or is converted to H2CO2 (85% of the time) by _____ ______ then dissociates to HCO3- and H+.

Answer 9

carbamate adducts; carbonic anhydrase

Question 10

alpha2 gamma2

Answer 10

HbF

Question 11

p50 of Hb

Answer 11

26 torr

Question 12

At position 6 of the B-globin gene, the amino acid change from ___ to Val⁶ confers sickle cell anemia

Answer 12

Glu⁶

Question 13

Sigmoidal binding curve = what type of cooperativity?

Answer 13

Positive; in Hb

Question 14

Alveolar partial pressure of O2 is ___ while the alveolar partial pressure of CO2 is ___

Answer 14

100 mmHg; 40 mmHg

Question 15

In the lungs, high pO2 drives binding of O2 to Hb, release of H+, and formation of H2CO3 (carbonic acid). Carbonic acid equilibrium favors synthesis of CO2 and H2O. What is the name of this effect?

Answer 15

Haldane Effect

Question 16

p50 of Mb

Answer 16

2.8 torr

Question 17

Fe-protoporphyrin IX =

Answer 17

Heme

Question 18

Weak ____ interactions are between the a1B1 and a2B2 heterodimers in Hb

Answer 18

Polar

Question 19

Myoglobin is made up of primarily what conformation of protein?

Answer 19

Alpha helices - 80%

Question 20

Hb Bart’s disease or hydrops fetalis is formed by how many alpha globin deletions?

Answer 20

4

Question 21

O2 binds to Hb _____

Answer 21

Cooperatively

Question 22

What are some causes of hereditary methemoglobinemia?

Answer 22

1. Mutations in the Pentose Phosphate Pathway, especially G-6-phosphate dehydrogenase deficiency
2. Glutathione- normally reduces reactive oxygen species
3. Mutations in cytochrome b5 reductase (NADH-dependent methemoglobin reductase)

Question 23

Shifting O2 binding curve to the right means there is a higher/ lower affinity for O2

Answer 23

Lower

Question 24

In RBCs, protons released by the dissociation of H2CO3 bind to Hb and favor the T state, favoring O2 release. What is this effect?

Answer 24

Bohr effect

Question 25

Carbamate adducts stabilize the __ conformation of Hb in the tissues and when reaches the lungs the high PO2 and low PCO2 causes a reversal of this reaction leading to expiration of CO2

Answer 25

T

Question 26

Type of Hb that makes up 97- 98.5% of total Hb in adult

Answer 26

HbA; a2B2

Question 27

HbF has a higher/lower affinity for oxygen than HbA. Why?

Answer 27

Higher; Binds 2,3-DPG poorly (gamma chains do not bind as well as beta chains in HbA) which shifts the curve to the left --\> the O2 that is released from the mother's HbA is bound to HbF and transferred to fetal tissue

Question 28

a-like globin genes are found on chromosome \_\_

Answer 28

16

Question 29

R (relaxed) form of Hb is the _____ form

Answer 29

Oxy form (O2 binding)

Question 30

Low pH favors O2 ____ to Hb and shifts the curve to the \_\_\_\_

Answer 30

Binding; right

Question 31

Movements of the proximal and distal _____ cause their attached a-helices to move that causes a conformational change at the interface of each aB dimer in the Hb molecule

Answer 31

histidines

Question 32

Which subunits bind together with strong hydrophobic interactions in Hb?

Answer 32

a1+B1 a2+B2

Question 33

Disease characterized by 3a globin gene deletions that forms a B₄ tetramer

Answer 33

HbH disease

Question 34

O2 is a ____ allosteric regulator of Hb O2 binding

Answer 34

Positive

Question 35

Type of Hb that is found in patients with homozygous sickle cell anemia that is also found in neonates

Answer 35

HbF

Question 36

T (taut) form of Hb is the _____ form

Answer 36

Deoxy (O2 release)

Question 37

Heme, chrolorphyll, Vit. B12 are all \_\_\_\_\_

Answer 37

Porphyrins

Question 38

In order for O2 to still bind Hb when 2,3-DPG is present, what is required?

Answer 38

Higher pO2

Question 39

B-like globin genes are found on chromosome \_\_

Answer 39

11

Question 40

Type of Hb that makes up 1.5 - 3% of total Hb in adult

Answer 40

HbA2

Question 41

Addition of 2,3-DPG would cause the O2 binding curve of Hb to shift to the \_\_\_\_

Answer 41

Right; allowing for more O2 to dissociate from Hb to supply O2 to the tissues operating at high metabolic rate

Question 42

How many O2 molecules does myoglobin bind?

Answer 42

1 O2

Question 43

Hb binds ___ O2

Answer 43

4

Question 44

\_\_\_\_\_\_ rings form coordinate covalent bonds to Fe2+ in heme

Answer 44

Pyrrole

Question 45

z2e2 or a2e2 or z2g2

Answer 45

HbE (embryonic)

Question 46

Hemoglobin is made up of 2 __ chains and 2\_\_ chains

Answer 46

2 alpha 2 beta

Question 47

The binding curve of Mb is ____ while the binding curve for Hb is \_\_\_\_

Answer 47

Hyperbolic; sigmoidal

Question 48

COPD, high altitudes, chronic anemia, and pregnancy causes an increase/decrease in 2,3-DPG

Answer 48

Increase

Question 49

Which form (deoxy or oxy) of HbS forms long polymers within the RBC that causes the sickle shape and short lifespan?

Answer 49

Deoxy

Question 50

High pH favors O2 ____ to Hb and shifts the curve to the \_\_\_\_

Answer 50

Relase; left

Question 51

Individuals homozygous for the B^s mutation, or heterozygous for the B^s and a B-thalassemia allele, produce significant amounts of _______ and have sickle cell disease

Answer 51

HbS (a2B^s2)

Question 52

PCO2, pH of blood and tissues,a and 2,3-DPG act as _____ allosteric regulators

Answer 52

negative; interaction at one site on Hb decreases O2 binding to heme at some distance from binding site of allosteric regulator

Question 53

Heme belongs to the class of pigments called \_\_\_\_\_\_\_

Answer 53

Porphyrins

Question 54

Type of Hb that is the major Hb from ~ 1 month gestation until near birth; ~40% at birth

Answer 54

HbF