Erythrocyte Biochemistry Flashcards

1
Q

What form of Iron does Heme carry?

A

Ferrous: Fe2+

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2
Q

What are the specific subunits for fetal hemoglobin?

A

HbF (alpha2, gamma2)

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3
Q

What is the current toxic chemotherapeutic agent used in research to induce HbF?

A

Hydroxyurea

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4
Q

What is the Proximal Histidine and what does it bind to?

A

F8 Histidine. It binds to heme.

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5
Q

What is the Distal Histidine and what does it bind to?

A

E7 Histidine: Oxygen binds to the iron between the heme and the distal histidine.

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6
Q

The binding of Oxygen to Fe of a global subunit pulls the ___________Histidine down.

A

Proximal F8

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7
Q

What are the 2 molecules used to store Iron? Which one is water soluble?

A
  1. Ferritin: water soluble

2. Hemosiderin: water insoluble.

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8
Q

What is the function of Ferric Reductase?

A

converts Fe3+ in non-heme iron(from plant products) to Fe2+

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9
Q

What is the function of DMT1(Divalent Transporter-1)

A

takes up Fe2+ into enterocyte

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10
Q

What is the function of Ferroportin?

A

Transports Fe2+ from enterocyte to the outside of the cell (blood and circulation).

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11
Q

What does Ferroportin require to transport iron to the outside of the cell(blood)?

A

Ferroxidase (Hephaestin, Cerruloplasmin).

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12
Q

What is the function of Hephaestin (Cerruloplasmin, Ferroxidase)?

A

Converts free iron( Fe2+) to Fe3+

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13
Q

What is the function of Transferrin?

A

Transports Iron (Fe3+) in the blood to bone marrow.

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14
Q

What peptide hormone regulates absorption of Iron?

A

Hepcidin

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15
Q

How does uptake of Tranferrin occur?

A

by receptor-mediated Endocytosis via transferrin receptors (TfR).
Internalized via clathrin coated pits(endosomes).

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16
Q

What is Hereditary Hemochromatosis?

A

It is an organ dysfunction due to Iron overload: cirrhosis, arthritis, skin pigmentation, cardiomyopathy.
Treatment is blood letting.

17
Q

What is the receptor of Hepcidin and how does it control it?

A

Ferroportin.
Binding of Hepcidin to Ferroportin causes internalization of Ferroportin; it is destroyed by proteolysis. Therefore, when Hepcidin expression is up, Ferroportin levels are down.

18
Q

What is Megaloblastic Macrocytic Anemia and what causes it?

A

Large erythrocytes/erythroblasts(megaloblasts). also hyper segmented neutrophils occur( more than 5 lobes-usually 3 to 4).
It is caused by a deficiency in Folic acid and Vitamin B12(Cobalamin).
Also occurs due to a diminished synthesis of DNA in developing RBCs in bone marrow.

19
Q

What are the 3 parts of Folic Acid?

A
  1. Pteridine ring
  2. PABA
  3. Glutamate residues chains
20
Q

What is the active form of Folate?

A

THF(tetrahydrofolate)

21
Q

What reduces Dihydrofolate to Tetrahydrofolate?

A

Dihydrofolate reductase

22
Q

What is the function of THF? In which process does it serve a VITAL role?

A

It transfers Carbon units from donors to acceptors.

Serves a vital role in DNA synthesis.

23
Q

When does the main Carbon transfer occur in the Folate Metabolism?

A

When the Carbon side chain of Serine is transferred to THF; forms N5,10-methyle THF. This carbon is then transferred to dUMP to form dTMP.

24
Q

Deficiency of Folic acid leads to_________

A

decrease in synthesis of DNA which leads to Megaloblastic Macrocytic Anemia.

25
Q

Where is Folic acid absorbed in the body?

A

In the small intestine: Jejunum.

26
Q

What is the primary form of THF in bloodstream? (this is also the same form as the THF that gets reduced in the intestine)

A

N5-methyl THF.

27
Q

What does N5-methyl THF require in order to be demethylated?

A

Requires Vitamin B12.

28
Q

What is a very important function of Vitamin B12(Cobalamin) duringg the Folate cycle?

A

It removes methyl group from N5-methyl THF to activate it.

29
Q

How is B12 absorbed?

A
B 12 bind to R-binder protein (made by the gastric mucosa cells). 
Intrinsic factors (made by parietal cella of stomach) carry B12 to Ileum where receptors bring it into body. (endocytosis)
30
Q

Cobalamin circulates through the blood carried by_____?

A

Transcobalamin

31
Q

What is Pernicious Anemia?

A

A Megaloblastic Macrocytic Anemia caused by a B12 deficiency (from unavailability of Intrinsic factors).