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CPR > Erythrocyte Biochemistry (Part 1) > Flashcards

Erythrocyte Biochemistry (Part 1) Flashcards

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1
Q

During erythropoiesis, an erythroblast transitions into a?

A

Normoblast

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2
Q

During erythropoiesis, what happens to a normoblast?

A

Its nucleus is expelled and it turns into a Reticulocytes and then eventually a RBC (erythrocyte)

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3
Q

During erythropoiesis, when is the majority of the Hemoglobin (Hb) synthesized?

A

BEFORE the nucleus is expelled from the normoblast

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4
Q

Fetal Hb

A

2 alpha chains and 2 gamma chains

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5
Q

Adult Hb (majority form)

A

2 alpha chains and 2 beta chains

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6
Q

Adult Hb (minority form)

A

2 alpha chains and 2 delta chains

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7
Q

Hemoglobin has 4 subunits (2alpha and 2beta), what is contained within each subunit?

A

1 heme bound to 1 iron (ferrous - Fe2+)

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8
Q

Before oxygen is bound, describe the orientation of the iron in Hb

A

OUTSIDE the plane of porphyrin

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9
Q

After oxygen is bound, describe the orientation of the iron in Hb

A

INSIDE the plane of porphyrin

- Pulls proximal Histidine down

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10
Q

Once oxygen is bound to the iron atom in Hb, what does this do to the proximal Histidine?

A

Pulls it down

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11
Q

What shape is the myoglobin oxygen dissociation curve?

A

Hyperbolic

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12
Q

What shape is the hemoglobin oxygen dissociation curve?

A

Sigmoidal

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13
Q

Why is the hemoglobin oxygen dissociation curve sigmoidal?

A

Positive Cooperativity!

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14
Q

What is Positive Cooperativity with Hb?

A

The binding of 1 oxygen to 1 heme facilitates binding of another oxygen to another heme

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15
Q

Why is Positive Cooperativity important?

A

Enhances oxygen delivery to tissues!

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16
Q

This molecule DECREASES oxygen affinity for Hb so more oxygen is delivered to tissues

A

2,3-BPG

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17
Q

Bohr effect results in a ____ shift of the oxygen dissociation curve

A

RIGHT

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18
Q

Describe the Bohr effect

A

Carbon dioxide and H+ produced by working tissues stimulates Hb to release oxygen
– Decreases Hb affinity for oxygen

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19
Q

Does HbF bind well to 2,3-BPG?

A

NO – thus the affinity for oxygen remains high in HbF

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20
Q

At what amino acid position # is the mutation for sickle cell anemia?

A

6

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21
Q

What is the mutation in sickle cell anemia?

A

Glutamic acid (-) is switched with Valine (hydrophobic)

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22
Q

Sickle shaped erythrocytes ______ circulation

A

Impede

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23
Q

Research on sickle cell anemia is being done to try and induce expression of?

A

HbF

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24
Q

Fe 2+

A

Ferrous

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25
Fe 3+
Ferric
26
Most of iron is contained in Hb, where is the rest?
Stored in cells of intestines, liver, spleen and bone marrow
27
Heme iron
Fe 2+
28
Where is Heme iron found?
Animal products
29
Non-Heme iron
Fe 3+
30
Where is Non-Heme iron found?
Plant products
31
What form of iron can be taken up from the intestinal lumen into Enterocytes?
Fe 2+ - Heme iron
32
What enzyme converts Non-Heme iron (Fe 3+) to Fe 2+?
Ferric Reductase
33
What transporter takes up Fe 2+ into Enterocytes once its converted from Fe 3+ in the intestinal lumen?
DMT-1
34
What enzyme in the Enterocyte converts Fe 2+ to Fe 3+?
Ferroxidase | Cerruloplasmin
35
If Fe 3+ is going to be stored in the Enterocyte, what is it stored as?
Ferritin
36
What is Ferritin (storage form of Fe 3+) degraded to?
Hemosiderin
37
What transporter takes Fe 2+ from the Enterocyte to the blood?
Ferroportin
38
What does Ferroportin require?
Hephastin
39
Once Fe 2+ is in the blood stream, it is converted to ____ by _____
Fe 3+ | Ferroxidase (Cerruloplasmin)
40
What is Fe 3+ bound to in the blood?
Transferrin
41
Transferrin's job?
Bind and transfer Fe 3+ to target tissues
42
How is Transferrin-Fe3+ taken up by target cells?
Receptor Mediated Endocytosis via TfR receptor
43
What causes Transferrin and its receptor to dissociate once in the endosome during receptor mediated endocytosis?
LOW pH
44
The endosome containing Transferrin-Fe3+ docks where in the cell?
Mitochondria
45
How does Hepcidin regulate Iron homeostasis?
It will bind Ferroportin and degrade it so iron cannot get into the blood stream
46
When iron is HIGH, what are the levels of Hepcidin, Ferroportin and iron absorption?
Hepcidin = HIGH Ferroportin = LOW Iron absorption = LOW
47
When iron is LOW, what are the levels of Hepcidin, Ferroportin and iron absorption?
Hepcidin = LOW Ferroportin = HIGH Iron Absorption = HIGH
48
What regulates iron homeostasis and where?
Hepcidin | -- At Ferroportin
49
What controls Hepcidin levels?
HFE
50
Hypochromic microcytic anemia
Iron Deficiency
51
Hemochromatosis
Iron Overload
52
How is Hemochromatosis inherited?
Autosomal Recessive
53
Deficiency in Folate AND Vitamin B12 (cobalamin) causes?
Megaloblastic Macrocytic Anemia
54
How do Erythrocytes appear with Megaloblastic Macrocytic Anemia?
LARGE - with normal Hb content
55
Describe Folate Metabolism
Folate Dihydrofolate (DHF) Tetrahydrofolate (THF)
56
What is the active form of Folate?
THF
57
What is the enzyme that converts Folate to DHF and THF?
Dihydrofolate Reductase
58
What is the main role of THF?
DNA synthesis
59
What is the main circulating form of Folate in the blood?
N^5 - methyl - THF
60
What does N^5 - methyl - THF require to be converted to THF, its active form?
Vitamin B12 (cobalamin)
61
What is the folate trap?
Without Vitamin B12, Folate will be stuck inactively in the form of N^5 - methyl - THF
62
What inhibits DNA synthesis by inhibiting Dihydrofolate reductase?
Methotrexate
63
Where is Vitamin B12 (cobalamin) found?
ONLY Animal products
64
Describe Vitamin B12 metabolism
B12 binds to R-binder proteins B12 binds to Intrinsic fact and dissociates from R-binder B12-IF travels to Ileum and enters blood stream Transcobalamin II carries complex in blood Complex taken up by cells via Receptor mediated Endocytosis
65
What carries the Vitamin B12 - Intrinsic Factor Complex in the blood?
Transcobalamin II
66
Pernicious Anemia
Vitamin B12 Deficiency due to lack of Intrinsic Factor
67
Is Pernicious Anemia a type of Megaloblastic Macrocytic Anemia?
Yes
68
What is the test to test for Pernicious Anemia?
Schiling Test
69
1st step of Schilling test
Administer radioactive B12 - Measure urine - - If B12 is present = Normal Absorption (def. diet) - - If B12 NOT present = NOT Absorbed - move on to step 2
70
2nd step of Schilling Test
Administer radioactive B12 + INTRINSIC FACTOR - Measure urine - If B12 is present = Pernicious anemia due to lack of intrinsic factor!

CPR (48 decks)

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