Myoglobin and Hemoglobin Flashcards

1
Q

How long will you see embryonic Hb present?

A

~ 1 week post-conception until birth

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2
Q

CO + heme in Hb (HbCO)=

A

Carboxyhemoglobin –>forms more readily than oxyhemoglobin (HbO2)

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3
Q

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

A

Bs mutation; sickle cell anemia

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4
Q

Methemoglobinemia is characterized by

A

Chocolate blood and cyanosis

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5
Q

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

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

CO binds very strongly to Hb

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6
Q

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

A

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

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7
Q

alpha2 delta2

A

HbA2

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8
Q

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

A

glucose; T

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9
Q

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+.

A

carbamate adducts; carbonic anhydrase

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10
Q

alpha2 gamma2

A

HbF

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11
Q

p50 of Hb

A

26 torr

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12
Q

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

A

Glu6

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13
Q

Sigmoidal binding curve = what type of cooperativity?

A

Positive; in Hb

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14
Q

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

A

100 mmHg; 40 mmHg

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15
Q

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?

A

Haldane Effect

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16
Q

p50 of Mb

A

2.8 torr

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17
Q

Fe-protoporphyrin IX =

A

Heme

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18
Q

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

A

Polar

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19
Q

Myoglobin is made up of primarily what conformation of protein?

A

Alpha helices - 80%

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20
Q

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

A

4

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21
Q

O2 binds to Hb _____

A

Cooperatively

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22
Q

What are some causes of hereditary methemoglobinemia?

A
  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)
23
Q

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

A

Lower

24
Q

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

A

Bohr effect

25
Q

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

A

T

26
Q

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

A

HbA; a2B2

27
Q

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

A

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

28
Q

a-like globin genes are found on chromosome __

A

16

29
Q

R (relaxed) form of Hb is the _____ form

A

Oxy form (O2 binding)

30
Q

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

A

Binding; right

31
Q

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

A

histidines

32
Q

Which subunits bind together with strong hydrophobic interactions in Hb?

A

a1+B1 a2+B2

33
Q

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

A

HbH disease

34
Q

O2 is a ____ allosteric regulator of Hb O2 binding

A

Positive

35
Q

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

A

HbF

36
Q

T (taut) form of Hb is the _____ form

A

Deoxy (O2 release)

37
Q

Heme, chrolorphyll, Vit. B12 are all _____

A

Porphyrins

38
Q

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

A

Higher pO2

39
Q

B-like globin genes are found on chromosome __

A

11

40
Q

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

A

HbA2

41
Q

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

A

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

42
Q

How many O2 molecules does myoglobin bind?

A

1 O2

43
Q

Hb binds ___ O2

A

4

44
Q

______ rings form coordinate covalent bonds to Fe2+ in heme

A

Pyrrole

45
Q

z2e2 or a2e2 or z2g2

A

HbE (embryonic)

46
Q

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

A

2 alpha 2 beta

47
Q

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

A

Hyperbolic; sigmoidal

48
Q

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

A

Increase

49
Q

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

A

Deoxy

50
Q

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

A

Relase; left

51
Q

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

A

HbS (a2Bs2)

52
Q

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

A

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

53
Q

Heme belongs to the class of pigments called _______

A

Porphyrins

54
Q

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

A

HbF