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Biochem > Hemoglobin, Myoglobin O2 Binding > Flashcards

Hemoglobin, Myoglobin O2 Binding Flashcards

1
Q

Describe myoglobin in 4 points

A
  1. O2 carrier in muscle cells
  2. Stores O2 in muscle cells
  3. Delivers O2 to mitochondria
  4. Binds O2 at low O2 levels
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2
Q

Describe hemoglobin in 5 points

A
  1. Oxygen carrier in the blood
  2. Binds O2 in lungs (pO2 ~ 100 mm Hg)
  3. Releases O2 in the tissues (pO2 ~ 20 mm Hg)
  4. Sensitive to small changes in O2 levels
    5, Carries CO2 from the tissues to the lungs
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3
Q

In lungs, CO2 is…

A

Released

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4
Q

RBCs in lungs…

A

High O2 levels favour O2 binding Hb

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5
Q

RBCs muscle…

A

Lower O2 levels favour release of O2 from Hb

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6
Q

In muscle, Mb, with its higher affinity for O2…

A

Takes up O2

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7
Q

As mitochondria oxidize fuel, they consume ____ and produce ____

A

O2; CO2

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8
Q

CO2 is released into the blood and…

A

Is transported as HCO3 or Hb-CO2

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9
Q

What do active sites of Mb and Hb contain?

A

A heme

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10
Q

Heme contains a ____ ____ with a single iron atom

A

porphyrin ring

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11
Q

The Fe can form what?

A

6 coordinate bonds (4 with pyrrole N in porphyrin ring plane; 1 with imidazole N from His in polypeptide chain; 1 with ligand (O2 or CO)

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12
Q

What does O2 only bind in the heme?

A

Reduced iron (Fe 2+)

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13
Q

Which heme doesn’t bind O2?

A

Fe3+ heme / methemoglobin HbMet

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14
Q

How many O2 binding sites does Mb have?

A

1

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15
Q

How many heme groups does Mb have?

A

1, which binds one molecule of O2

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16
Q

How many O2 binding sites does Hb have?

A

4

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17
Q

How many polypeptide chains does Hb have?

A

4, each with heme to bind an O2

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18
Q

Due to its ____ affinity for O2, Mb would release ________ O2 between 10 and 100 mmHg of O2

A

high; very little

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19
Q

Due to its ___ affinity for O2, Hb can release _____ O2 between 10 and 100 mmHg of O2

A

low; more

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20
Q

O2 binding to Hb displays what?

A

Positive cooperativity

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21
Q

Mb is more or less responsive to changes in O2 conc?

A

less responsive

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22
Q

What shaped curve is characteristic of positive cooperativity?

A

sigmoid shaped curve

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23
Q

How many ligand binding sites do you need for + coop?

A

At least 2

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24
Q

How many receptor confirmations do you need for + coop?

A

At least 2

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25
Q

Does the first ligand bound have higher or lower affinity than subsequent ligands?

A

Lower, e.g. larger Kd

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26
Q

What confirmation has a low affinity for O2?

A

T or taut

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27
Q

What confirmation have a high affinity for O2?

A

R or relaxed

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28
Q

Where is T prevalent?

A

At low O2 in tissues

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29
Q

Where is R prevalent?

A

At high O2 in lungs

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30
Q

Interface of ____ _____ different in R and T state

A

alpha/beta dimers

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31
Q

Where is Fe in absence of O2?

A

Out of heme plane, which stabilizes T confirmation

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32
Q

Where is Fe in presence of O2?

A

Pulled back into the heme plane, which stabilizes the R confirmation and high affinity binding at other O2 binding sites

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33
Q

Hill coefficient for Mb-O2 binding

A

1

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34
Q

Hill coefficient for Hb-O2 binding

A

> 1

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35
Q

Positive cooperativity is a form of…

A

Allostery

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36
Q

What kind of modifier is O2?

A

Homotropic allosteric modifier

37
Q

Heterotropic allosteric modifiers are…at the active site

A

Heterotropic allosteric modifiers are different from the ligand at the active site

38
Q

Heterotropic inhibitors stabilize which form of the active site?

A

low affinity form

39
Q

Heterotropic activators stabilize which form of the active site?

A

high affinity form

40
Q

List the 3 heterotropic inhibitors of O2 binding to Hb

A

pH (H+)

CO2

BPG

41
Q

An decrease in pH….

A

Decreases the amount of O2 bound to Hb

42
Q

H+ does not bind to…

A

O2 site (e.g. does not bind to Fe in heme)

43
Q

What does H+ bind to?

A

His146 in the beta subunit, stabilizing an ionic bond (His146-Asp94) in the T-state

44
Q

What happens when H+ is lowered and pH is raised?

A

Ionic bond between His146 and Asp94 is lost and R-state becomes more stable

45
Q

What kind of bond does CO2 form in relation to Hb? What does this reaction release?

A

A covalent bond with terminal amine group of Hb. This reaction releases H+

46
Q

When CO2 binds with terminal amine group of Hb, the terminal carbamino group does what?

A

Stabilizes the T state

47
Q

What is BPG?

A

Byproduct of anaerobic glycolysis (RBCs only support glycolysis)

48
Q

Where does BPG bind Hb?

A

At a site distant from O2 binding site

49
Q

CO poisoning causes how many yearly poisoning deaths world wide?

A

1/2

50
Q

What does CO compete with in Hb?

A

O2 for heme site

51
Q

Who is susceptible to CO poisoning?

A

Fetuses

52
Q

CO binding at Hb active site has ___ and ____ effects

A

non-allosteric; allosteric

53
Q

What is an allosteric effect of CO bound at active site

A

CO bound at active site increases O2 binding at other active sites

54
Q

What is a non-allosteric effect of CO poisoning?

A

CO competes with O2 binding at the active sites

55
Q

What is the major adult form of Hb?

A

Hb A

56
Q

Composition of Hb A

A

alpha2beta2, 95% to 98%

57
Q

What is the minor form of Hb?

A

Hb F

58
Q

Composition of Hb F?

A

alpha2gamma2, 0.8% to 2%

59
Q

What is the major Hb in fetus and newborn?

A

Hb F

60
Q

Which form has a higher affinity for O2? Hb A or Hb F?

A

Hb F

61
Q

Which type of Hb doesn’t bind well to BPG?

A

Hb F

62
Q

What is the Sickle Cell form of Hb?

A

Hb S

63
Q

Describe Hb S

A

beta 6 Glu -> Val (alpha2betas2) )%

64
Q

Describe Hb M

A

beta59 His -> Tyr (alpha2betam2) 0%

65
Q

Describe thalassemia

A

Mutations lead to impaired synthesis of alpha or beta chains

Complete lack of alpha chains usually fatal in utero

66
Q

What kind of mutation is in Sickle Cell Anemia?

A

Missense mutation in beta globin gene

67
Q

In Hb S mutation from Glu to Val, How many negative charges are lost?

A

2

68
Q

In the T-confirmation, beta Val-6 on Hb surface exposes what?

A

hydrophobic patch

69
Q

HbS associates via what?

A

Hydrophobic patches

70
Q

What give RBCs their sickle shape?

A

Insoluble fibers of HbS polymers

71
Q

What happens to HbS especially under anoxic conditions?

A

HbS polymerizes, forming long strands

72
Q

Because sickle cells are more fragile, what results?

A

Anemia because of hemolysis, thereby fewer RBCs

72
Q

HbS forms ___ fibers on deoxygenation

A

insoluble fibers (gives RBCs sickle shape)

73
Q

What leads to inflammation in Sickle Cell Anemia?

A

Free heme and broken RBCs

74
Q

What occurs in a vaso-occlusive crisis?

A

Severe pain, inadequate O2 (ischemia) and uncontrolled cell death (necrosis)

75
Q

Sickle cells are ____ _____ and highly _____

A

Sickle cells are less flexible and highly adhesive

76
Q

Due to the limited flexibility and high adhesive nature of sickle cells, what occurs in the body?

A

It occludes blood flow (infarct) to almost every oran in the body

77
Q

What are 6 contributing factors to SCD?

A
  1. Desoxygenation*
  2. Dehydration*
  3. Fever
  4. Stress situation
  5. General anaesthesia
  6. Acidosis*
78
Q

What chromosome mutation leads to SCD?

A

Mutation of chromosome 11

79
Q

Desoxy-Hemoglobin formation (HbS) -> _______ -> Insoluble HbS polymers

A

Desoxy-hemoglobin formation (HbS) leads to

Lower O2 partial pressure and polymerization, which leads to

Insoluble HbS polymers

80
Q

Insoluble HbS polymers lead to which 2 things?

A
  1. Reduced deformation of RBCs & vaso-occlusion
  2. Rigidification and fragmentation of RBCs
81
Q

What 3 things stem from reduced deformation of RBCs & vaso-occlusion?

A
  1. Osteonecrosis
  2. Bone infarction
  3. Osteomyelitis
82
Q

What happens after rigidification & fragmentation of RBCs?

A

Hemolysis:
1. Anemia fewer RBCs (mucosal pallor)
2. Free heme (discolouration of gingiva)
3. RBC membrane, free heme released (inflammation)

83
Q

What 5 things can happen when there is reduced blood flow/O2 in SCD?

A
  1. Osteomyelitis, Orofacial pain
  2. Atrophy lingual papillae
  3. Pulpitis, pulp necrosis
  4. mental nerve neuropathy
  5. Asplenia - impaired immune system
84
Q

Pallor of oral mucosal happens with…

A

Chronic hemolysis, decreased RBCs

85
Q

Atrophy of lingual papillae happens with…

A

Vaso occlusion and decreased blood flow

86
Q

What leads to neuropathy of the mental nerve and labial hypoaesthesia (NCS)?

A

Vaso occlusion and ischemia of the inferior alveolar nerve

87
Q

What leads to pulpitis and necrosis?

A

Vaso occlusion and ischemia of the pulp microcirculation

Biochem (6 decks)

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