Lec 10 Erythrocyte Biochem Flashcards

1
Q
A
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2
Q

Erythropoiesis steps

A
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3
Q

What are the subunits on hemoglobin?

A

2 alpha globin chains

2 beta globin chains

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4
Q

how many heme per subunit?

What form of iron in heme?

Function and characteristic of heme?

A

1

Ferrous Fe2+

Carries O2 and is hydrophobic

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5
Q

Types of heme?

A

Embryonic

fetal

adult

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6
Q

Embryonic heme

A

Gower and portland up to 8 weeks (embryo)

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7
Q

Fetal hemoglobin heme type and presence

A

HbF (alpha gamma)

At 10 weeks alpha and gamma rise gamma fall near birth

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8
Q

Adult heme and presence

A

HbA aplpha and beta

beta rises around birth alpha already present

Hb A2 rarer

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9
Q

sickle cell anemia heme and research

A

Hbs

research ongoing to induce expression of HbF

(hydroxyurea)

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10
Q

What binds to heme?

A

F8 histidine

(proximal histidine)

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11
Q

What stabalizes bond between heme and O2

A

Distal histamine (E7)

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12
Q

Conformational change

A
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13
Q

Myoglobin oxygen dissociation curve?

A

hyperbolic more to the left

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14
Q

Hemoglobin oxygen dissociation curve shape?

A

sigmoidal (due to interactions between subunits)

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15
Q

Cooperativity in hemoglobin

A
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16
Q

Oxygen dissociation curve (release of O2)

A

Bohr Effect

pH of active tissues lower

binding affinity decreases with pH

histidine is bound with H+

conformation chang of Hb favors O2 release

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17
Q

2,3 bisphosphoglycerate

A

reduces 02 affinity so Hb gives up O2 to tissues

signal Hb to let go of O2

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18
Q

the curve and exercise

A

has pO2 drop from 40 to 20 torr which is steepest part of curve so very effective in providing oxygen to tissues

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19
Q

The curve and HbF and HbA

A

Fetus needs Hb that has higher affinity for O2 than mothers (left shift)

HbF does not bind well to 2,3 BPG (cause for affinity diff)

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20
Q

Iron cycle basic process

A
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21
Q

Iron distribution

A

Hemoglobin 67%

storage iron 27%

ferritin-H20 sol

hemosiderin-H20 insol

Myoglobin 5%

Fe-requiring proteins 1%

22
Q

Iron from intestinal lumen to Enterocyte

A

Heme just goes through ferroxidase to Ferrous iron (Fe 2+)

ferric iron (3+) is converted into ferrous iron via Duodenal cytochrome B

Fe2+ then goes through DMT1

(divalent transporter 1)

23
Q

FRom enterocyte to blood Fe

A

Fe2+ leaves via ferroportin

24
Q

Storage in enterocyte of Fe

A

Fe2+ to Fe3+ then stored in ferritin

which can be degraded to hemosiderin

25
Q

Free Fe2+ in blood?

A

ferroxidase helps Fe2+ to Fe3+ which is transported by transferrin to tissues

26
Q

When transferin reaches cells?

A

uptake occurs by receptor mediated endocytosis (transferin receptor)

Mitochondria uptake (heme made here) effecient

DMT1 transports iron out of endosome

27
Q

Hypochromic microcytic anemia

A

low iron

less iron that are smaller

treatment is dietary iron supp

28
Q

Iron deficiency causes

A

diet iron low

menstruating women

aspirin overuse

ulcers of GI

29
Q

Hereditary hemochromatosis

A

Iron overload organs: cirrhosis arthritis

cardiomyopathy

3 to 5 g normal here 15g

treatment blood letting

30
Q

Role of Hepcidin

A

binds to ferroportin which causes internalization of ferroportin

ferroportin destroyed by proteolysis

31
Q

Iron levels and hepcidin

A

iron is high? hepcidin expression up ferroportin levels down, iron absorption low

When iron is low? hepcidin down ferroportin up iron absorption high

32
Q

regulation of hepcidin expression

A

Hfe is supposed to bind Tfr2 which turns on expression of hepcidin

if Hfe is mutated it will not and no hepcidin so no control of ferroportin activity (increased iron)

33
Q

RBC production dependent on what?

A

vit B12 and Folate (folic acid)

34
Q

deficiency in B12 and folate leads to what?

A

megaloblastic anemia (Due to DNA synthesis impairment in bone marrow)

35
Q

Megaloblastic macrocytic anemia

A

deficiency in B12 and folate

large erythrocytes with normal hemoglobin content

36
Q

Megablastic macrocytic anemia Pic

A
37
Q

Changes in bone marrow in megaloblastic macrocytic anemia

A
38
Q

How many parts does folic acid have?

A

3 parts

39
Q

Folate in the diet comes in as? what does it need to become? what catalyzes this?

A
40
Q

Main function of tetrahydrofolate (THF)

A

a one carbon donor for synthesis of nucleotides

uses 2 N

41
Q

Tetrahydrofolate (THF) and carbon

A

THF gets carbon side chain of serine changes to N5,10-methylene-THF which transfers carbon to deoxyuridylate forms dTMP

42
Q

Folic acid is absorbed where?

A

small intestine jejunum

43
Q

What stores folic acid?

A

liver stores 5-10 mg which can last 3 to 6 months

44
Q

primary form of folic acid in bloodstream?

A

N5 methyl THF

45
Q

B12 and folate

A

N5 methyl THF requires vitamin B12 (cobalamin) to become demethylated (or else it is stuck as N5)

creates methyl-cobalamin release THF

46
Q

Vit b12 is from what? deficiency?

A

not in plant products

deficiency is very rare

47
Q

B12 absorption

A

R-binder proteins (gastric mucosa) bind B12

R-binder degraded by proteases in duodenum

intrinsic factor carries B12 to ileum where receptors bring into body

48
Q

how is intrinsic factor-cobalamin absorbed?

A

VIA RECEPTOR MEDIATED ENDOCYTOSIS

49
Q

Pernicious Anemia

A
50
Q

Schilling test part 1

A
51
Q

Schilling Test part two

A