Lec 10 Erythrocyte Biochem

Question 2

Erythropoiesis steps

Answer 2

Question 3

What are the subunits on hemoglobin?

Answer 3

2 alpha globin chains

2 beta globin chains

Question 4

how many heme per subunit?

What form of iron in heme?

Function and characteristic of heme?

Answer 4

1

Ferrous Fe2+

Carries O2 and is hydrophobic

Question 5

Types of heme?

Answer 5

Embryonic

fetal

adult

Question 6

Embryonic heme

Answer 6

Gower and portland up to 8 weeks (embryo)

Question 7

Fetal hemoglobin heme type and presence

Answer 7

HbF (alpha gamma)

At 10 weeks alpha and gamma rise gamma fall near birth

Question 8

Adult heme and presence

Answer 8

HbA aplpha and beta

beta rises around birth alpha already present

Hb A2 rarer

Question 9

sickle cell anemia heme and research

Answer 9

Hbs

research ongoing to induce expression of HbF

(hydroxyurea)

Question 10

What binds to heme?

Answer 10

F8 histidine

(proximal histidine)

Question 11

What stabalizes bond between heme and O2

Answer 11

Distal histamine (E7)

Question 12

Conformational change

Answer 12

Question 13

Myoglobin oxygen dissociation curve?

Answer 13

hyperbolic more to the left

Question 14

Hemoglobin oxygen dissociation curve shape?

Answer 14

sigmoidal (due to interactions between subunits)

Question 15

Cooperativity in hemoglobin

Answer 15

Question 16

Oxygen dissociation curve (release of O2)

Answer 16

Bohr Effect

pH of active tissues lower

binding affinity decreases with pH

histidine is bound with H+

conformation chang of Hb favors O2 release

Question 17

2,3 bisphosphoglycerate

Answer 17

reduces 02 affinity so Hb gives up O2 to tissues

signal Hb to let go of O2

Question 18

the curve and exercise

Answer 18

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

Question 19

The curve and HbF and HbA

Answer 19

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)

Question 20

Iron cycle basic process

Answer 20

Question 21

Iron distribution

Answer 21

Hemoglobin 67%

storage iron 27%

ferritin-H20 sol

hemosiderin-H20 insol

Myoglobin 5%

Fe-requiring proteins 1%

Question 22

Iron from intestinal lumen to Enterocyte

Answer 22

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)

Question 23

FRom enterocyte to blood Fe

Answer 23

Fe2+ leaves via ferroportin

Question 24

Storage in enterocyte of Fe

Answer 24

Fe2+ to Fe3+ then stored in ferritin

which can be degraded to hemosiderin

Question 25

Free Fe2+ in blood?

Answer 25

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

Question 26

When transferin reaches cells?

Answer 26

uptake occurs by receptor mediated endocytosis (transferin receptor) Mitochondria uptake (heme made here) effecient DMT1 transports iron out of endosome

Question 27

Hypochromic microcytic anemia

Answer 27

low iron less iron that are smaller treatment is dietary iron supp

Question 28

Iron deficiency causes

Answer 28

diet iron low menstruating women aspirin overuse ulcers of GI

Question 29

Hereditary hemochromatosis

Answer 29

Iron overload organs: cirrhosis arthritis cardiomyopathy 3 to 5 g normal here 15g treatment blood letting

Question 30

Role of Hepcidin

Answer 30

binds to ferroportin which causes internalization of ferroportin ferroportin destroyed by proteolysis

Question 31

Iron levels and hepcidin

Answer 31

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

Question 32

regulation of hepcidin expression

Answer 32

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)

Question 33

RBC production dependent on what?

Answer 33

vit B12 and Folate (folic acid)

Question 34

deficiency in B12 and folate leads to what?

Answer 34

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

Question 35

Megaloblastic macrocytic anemia

Answer 35

deficiency in B12 and folate large erythrocytes with normal hemoglobin content

Question 36

Megablastic macrocytic anemia Pic

Answer 36

Question 37

Changes in bone marrow in megaloblastic macrocytic anemia

Answer 37

Question 38

How many parts does folic acid have?

Answer 38

3 parts

Question 39

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

Answer 39

Question 40

Main function of tetrahydrofolate (THF)

Answer 40

a one carbon donor for synthesis of nucleotides uses 2 N

Question 41

Tetrahydrofolate (THF) and carbon

Answer 41

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

Question 42

Folic acid is absorbed where?

Answer 42

small intestine jejunum

Question 43

What stores folic acid?

Answer 43

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

Question 44

primary form of folic acid in bloodstream?

Answer 44

N5 methyl THF

Question 45

B12 and folate

Answer 45

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

Question 46

Vit b12 is from what? deficiency?

Answer 46

not in plant products deficiency is very rare

Question 47

B12 absorption

Answer 47

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

Question 48

how is intrinsic factor-cobalamin absorbed?

Answer 48

VIA RECEPTOR MEDIATED ENDOCYTOSIS

Question 49

Pernicious Anemia

Answer 49

Question 50

Schilling test part 1

Answer 50

Question 51

Schilling Test part two

Answer 51