Lecture 6: Erythrocyte Biochemistry Part 1 Flashcards

1
Q

What is the pathway of erythropoiesis?

A

HSC > committed cell > ribosome synthesis (phase 1) > Hb accumulation (phase 2) > nucleus ejection (phase 3) > erythrocyte

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2
Q

What does adult Hb contain?

What does fetal Hb contain?

A

Adult: Hb A (2a, 2B or 2D)
Fetal: Hb F (2a2Y)

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3
Q

What is the structure of adult Hb?

A

Each globin chain has a heme in the center (iron + porphyrin ring) that carries the O2

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4
Q

What happens to Hb structure after O2 binds?

A

Iron molecule aligns with plane of the porphyrin ring > pulls proximal His of globin chains > conformational change > cooperativity

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5
Q

What is the role of the distal His residue of the globin chain?

A

Stabilizes bound O2

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6
Q

Why does myoglobin have a hyperbolic and hemoglobin a sigmoidal dissociation curve?

A

Myoglobin has higher O2 affinity and no cooperativity

Hemoglobin has lower O2 affinity and exhibits cooperativity

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7
Q

What does cooperativity mean?

A

Binding/removal of O2 from one globin chain = easier binding/removal to other globin chains&raquo_space;> sigmoidal curve

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8
Q

How does pH change affect the ODC?

A

Low pH in tissues = right shift (Bohr effect) in the tissues

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9
Q

How does 2,3, BPG bind to affect the ODC?

A

It binds to Hb, reducing affinity to O2 = right shift

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10
Q

How does exercise affect ODC?

A

Decrease pO2 = Hb releases O2 to tissues = right shift

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11
Q

What is the difference between fetal and maternal Hb?

A

Fetal Hb has higher affinity to O2 and does not bind 2,3, DPG (leftward ODC compared to adult)

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12
Q

Sickle Cell anemia
Cause
Tx

A
  • Glu to Val (hydrophobic) mutation causes Hb to clump together and form C shaped RBCs, blood can’t effectively squeeze through capillaries due to its shape
  • Hydroxyurea replaces defective hemoglobin with fetal hemoglobin
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13
Q

What major physiological processes does Iron participate in?
At what level is body iron regulated?

A

O2 transport via Hb and ETC as part of cytochrome

By controlling absorption

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14
Q

What are the major storage proteins for iron?

A

Ferritin (binds ferric iron)

Hemosiderin (product of ferritin breakdown)

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15
Q

Draw the pathway of Iron absorption

A

Ok

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16
Q

How is transferrin processed in the cells?

A

Binds TfR > taken up by coated pits > forms low pH endosome > transferrin removed from TfR (which is recycled) > transported into MT by DMT-1

17
Q

What molecule regulates the absorption of iron and how does it do so?

A

Hepcidin binds to ferroportin transporter in the enterocyte > lysosomes degrade the gate > no gate = no entry

18
Q

What regulates Hepcidin production?

A

HFE (human homeostatic iron regulator protein (HFE)

19
Q

What does it mean to be iron deficient or overloaded?

A

Refers to absorption of iron, not necessarily levels

20
Q

Iron deficiency
Possible causes
What type of anemia results?
Treatment

A
  • insufficient diet or absorption, bleeding, aspirin overuse
  • Hypochromic microcytic anemia
  • iron supplements
21
Q

Hereditary Hemochromatosis/HH
Causes
Clinical

A
  • HFE mutation (autosomal recessive) leading to iron overload, accumulates in viscera
  • results in cirrhosis, liver cancer, DM, arthritis or heart failure, 15 g total body iron (normal 3-5 g)
22
Q

What two things is RBC production dependent on?

A

Folate and cobalamin (vit. B9 and b12)

23
Q

Megaloblastic Macrocytic Anemia
Cause
Clinical (how do blood cells look?)

A
  • B9 and B12 deficiency

- Large erythrocytes >100 fL (but normal Hgb levels), large erythroblasts in bone marrow, hypersegmented neutrophils

24
Q

What makes up the structure of folate?

A

Pteridine ring, PABA and glutamate residues

25
Draw the pathway for folate metabolism
Ok
26
Why is folate important for RBC maturation?
Important for purine and thymine synthesis. Deficiency causes megaloblastic macrocytic anemia
27
How is folate absorbed?
In jejunum, reduced to and circulates as N5-methyl THF
28
Why is B12 important in RBC maturation?
It converts circulating folate to active THF by removing the methyl (avoid folate trap) and also using it for purine and pyrimidine synthesis
29
What is methotrexate?
Analog of DHF that inhibits DHF reductase | Chemo drug that prevents DNA synthesis in cancer cells
30
What is the usual cause and effects of Vit. B12 deficiency?
Lack of Intrinsic factor, causes megaloblastic macrocytic anemia
31
What is the role of intrinsic factor in B12 absorption?
Eaten b12 binds to R-binder, IF replaces R-binder and transports B12 to bloodstream. IF-B12 is taken up by cells for use
32
What is the usual cause of pernicious anemia?
IF deficiency (can't absorb B12), type of MM Anemia
33
What is a Schilling test and how is it performed?
Tests b12 and folate levels Part 1: Pt given radioactive B12. Urine checked for B12 presence. If absent, B12 isn't absorbed = pernicious anemia Part 2: Pt given radioactive B12 + IF. Urine checked for B12. If now present, that means adding IF was missing in patient