Chapter 15- Hemoglobin Flashcards

1
Q

_____ stores O2 in the muscles

A

Myoglobin (Mb)

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2
Q

_____ transports O2 in the blood

A

Hemoglobin (Hb)

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3
Q

How many units of O2 can Mb store? Hb?

A

Mb- 1
Hb- 4

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4
Q

Which group does the O2 bind to?

A

Heme group

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5
Q

How many heme groups does Mb contain? Hb?

A

Mb- 1
Hb- 4

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6
Q

Heme groups consist of:

A
  1. A porphyrin derivative (pyrrole rings linked by methane bridges)
  2. Centrally bound iron atom (Fe (II))
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7
Q

A heme group is called a ____ _____

A

prosthetic group

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8
Q

The iron atom in the heme group normally remains in the ____ oxidation state

A

Fe (II)

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9
Q

Color of deoxyHb? oxyHb?

A

Dark purplish
Brilliant red

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10
Q

Mb and Hb possess reversible action which means they can

A

bind O2 and release it.

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11
Q

Lower value of Kd means _____ affinity

A

higher

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12
Q

Lower value of Ka means _____ affinity

A

lower

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13
Q

Higher affinity means _____ binding

A

stronger

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14
Q

Mb-O2 dissociation follows a _____ curve

A

hyperbolic

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15
Q

Why do muscles need O2?

A

O2 is used by muscles to form ATP

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16
Q

When is Mb most saturated?

A

The oxygen concentrations are high (aka the muscle is resting)

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17
Q

O2 binding to Hb follows a _____ curve

A

sigmoidal

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18
Q

The sigmoidal curve of O2 binding in Hb is indicative of a ____ _____

A

cooperative process

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19
Q

Mb is ill-suited for the ______ of O2, which means its more suited as an ___ ______ ______

A

transport
O2 storage protein

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20
Q

How does Hb solve the problem of being able to bind and release O2?

A

A cooperative transition from low affinity to high-affinity state

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21
Q

Two conformations for Hb

A

T state- tensed
R state- relaxed

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22
Q

binding of O2 in Hb leads to ______ _____

A

conformational changes

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23
Q

Binding of O2 is a form of _______ ______

A

Allosteric Binding

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24
Q

What does allosteric binding mean in terms of O2 binding

A

The binding of a ligand to one site affects the binding properties of another site on the same protein

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25
Q

The conformational changes of binding sites of Hb make it easier for

A

O2 to bind

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26
Q

After first O2 binds, affinity _____ _______

A

Increases 100-fold

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27
Q

In deoxyhemoglobin, Fe 2+ is ____ spin

A

high

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28
Q

When O2 binds, Fe2+ is ____ spin

A

low

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29
Q

IF nH= 1

A

Binding is not cooperative

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30
Q

Mb has an n= ?

A

1

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31
Q

nH> 1 means

A

Positive cooperativity (Hb)

32
Q

nH < 1

A

Negative cooperativity

33
Q

What does negative cooperativity mean?

A

binding of one ligand impedes the binding of others.

34
Q

What does nH correspond to?

A

the degree of cooperativity between binding sites

35
Q

n of Hb=?

A

2.8

36
Q

What is n?

A

the slope of the Hill plot

37
Q

What is the upper limit of nH? what does it mean in terms of binding?

A

nH=n, all binding sites bind ligand simultaneously

38
Q

The affinity of Hb changes as ____ changes

A

pO2

39
Q

The hill plot of Hb is

A

curvilinear

40
Q

At low pO2, Y~

A

0

41
Q

At low pO2, Hb subunits compete ___ for O2 and the Hill plot has a slope of ___

A

independently, 1

42
Q

At high pO2, Y~

A

1

43
Q

At low pO2, how many O2 have bound to the Hb?

A

Most likely 0, few have bound 1

44
Q

At high pO2, how many O2 have bound to the Hb?

A

at least 3/4 of binding sites are occupied

45
Q

Which pO2 level has the maximum cooperativity?

A

intermediate pO2

46
Q

The slope of the Hill plot at high pO2?

A

slope =1

47
Q

The slope of the Hill plot at intermediate pO2?

A

slope ~3

48
Q

the differential affinity of Hb for O2 in the lungs and peripheral tissues stems from ______ ____ which are ______ ______

A

effector molecules, allosteric effectors

49
Q

Oxygen is a ____ and _____ allosteric effector

A

positive, homotropic

50
Q

the other three allosteric effectors of O2

A
  • CO2
  • H+
  • 2,3 BPG
51
Q

CO2, H+, and 2,3 BPG are _____ and _____ allosteric effectors which means they promote the _____

A

Negative, Heterotropic, dissociation of O2

52
Q

pH in the lungs=_____
pH in tissues = ______

A

7.6 in the lungs
7.2 in the tissues

53
Q

The tissues possess a ___ pH and a ____ [CO2]

A

low, high

54
Q

The affinity of Hb for O2 is ____ in the tissues which means O2 is ______

A

decreased, released

55
Q

The lungs possess a ____ pH and a ____ [CO2]

A

high, low

56
Q

The affinity for Hb for O2 is ____ in the lungs which means O2 _____

A

increased, Binds

57
Q

Bohr Effect

A

The effect of pH and [CO2] on Hb binding

58
Q

The H+ effect states

A

protonation of HIS146 is responsible for stabilizing the T state

59
Q

The CO2 effect states

A

CO2 binds as a carbamate group to the N-term of each subunit which forms additional salt bridges stabilizing the T state

60
Q

The CO2 effect leads to the production of ____

A

H+

61
Q

BPG binds tightly to deoxyHb in a ____ ratio

A

1:1

62
Q

BPG stabilizes the ______

A

T state

63
Q

BPG inhibits O2 binding on ______ subunits of Hb

A

all 4

64
Q

Without BPG little O2 would be _____

A

released by Hb

65
Q

Synthesis of BPG increases when exceeding altitudes above _____

A

4,000m

66
Q

Increased BPG causes a small difference in _____ and a large difference in _____

A

O2 binding in the lungs, O2 release in tissues

67
Q

Newborn babies after birth will synthesize more ____ than ____ subunits

A

gamma, beta

68
Q

Fetal Hb has _______ than maternal Hb

A

greater affinity

69
Q

How can a fetus extract enough O2 from the mother’s blood?

A

Fetus synthesizes gamma subunits instead of beta which results in a tetramer with a lower affinity for BPG

70
Q

Sickle cell anemia (HbS) is caused by a ______ which changed _____ to ____ in the beta chain

A

single mutation, Glu to Val

71
Q

The mutation for HbS occurs on the _____ of Hb which creates a ________

A

surface, Hydrophobic spot

72
Q

The hydrophobic spot on the HbS will form _____ which distorts RBC shape

A

Fibrils

73
Q

How is sickle cell treated?

A

Hydroxyurea and CRISPR gene editing

74
Q

How does hydroxyurea partially treat sickle cell anemia?

A

elevates the expression of fetal gamma subunit

75
Q

Why is sickle cell anemia not observed until several months after birth?

A

That is when the fetal gamma subunit mutates into beta S subunit