Heme, Iron and Bilirubin Metabolism

Question 1

hemoglobin

Answer 1

heme - iron

globin - two pairs of chains

Question 2

heme

Answer 2

porphrin ring with one iron chelated by 4 nitrogens

reversible oxygen attachment

Question 3

heme synthesis

Answer 3

succinyl CoA and glycine > ALA
ENZ - ALA synthase
-rate limiting step

heme - negative feedback inhibitor

2x ALA > prophobilinogen
ENZ - PBG synthase - ALA dehydratase

condensation of 4 x porphobilinogen > protoporphyrin

Fe added to protoporphyrin
ENZ - ferrochelatase

Question 4

sideroblastic anemia

Answer 4

mutation of ALA synthase

Question 5

porphyria

Answer 5

mutation in porphobilinogen synthase or PBG deaminase

Question 6

Pb poisoning

Answer 6

affects ALA dehydratase

Question 7

ALA synthase

Answer 7

rxn in mitochondria

Question 8

ALA dehydratase

Answer 8

rxn in cytosol

Question 9

ferrochelatase

Answer 9

rxn back into mitochondria

Question 10

alpha globins

Answer 10

chromosome 16

Question 11

beta globins

Answer 11

chromosome 11

Question 12

thalassemia

Answer 12

disruption of balance of globin chain synthesis

Question 13

Hb gower

Answer 13

embryonic

Question 14

portland Hb

Answer 14

fetal

Question 15

HbA

Answer 15

in adults

Question 16

majority HbA

Answer 16

alpha2beta2

Question 17

heme and globin

Answer 17

combine in cytoplasm

Question 18

transferrin

Answer 18

carries iron

Question 19

ferrous

Answer 19

Fe2+

Question 20

Hg only binds

Answer 20

ferrous - Fe2+

Question 21

ferrous bonds

Answer 21

4 - heme
1 - globin
1 - oxygen

Question 22

iron absorption

Answer 22

duodenum

Question 23

ferric

Answer 23

Fe3+

Question 24

ferric reductase

Answer 24

DcytB

-Fe3+ to Fe2+

Question 25

DMT1

Answer 25

cotransport Fe2+/H+ into cell

Question 26

ferroportin

Answer 26

transport Fe2+ out of cell regulated by hepcidin levels

Question 27

hepicidin

Answer 27

regulator of ferroportin | -Fe transport out of cell

Question 28

hemochromatosis

Answer 28

high levels of Fe

Question 29

heme oxygenase

Answer 29

inside cells | -splits heme iron and releases free Fe3+

Question 30

high Fe levels

Answer 30

high hepcidin | -decreased ferroportin

Question 31

low Fe levels

Answer 31

low hepcidin - increased ferroportin - more absorption from gut

Question 32

transport in blood

Answer 32

Fe3+ on transferrin

Question 33

ferritin

Answer 33

storage of Fe Fe + apoferritin

Question 34

apoferritin

Answer 34

iron buffer system

Question 35

HAMP mutation

Answer 35

decreased hepcidin iron overload and hemochromatosis

Question 36

RBC breakdown

Answer 36

120 days -in spleen no spleen - to liver

Question 37

RBC metabolism

Answer 37

glycolysis - ATP and NADH | pentose phosphate - NADPH to maintain reduced glutathione

Question 38

fava beans

Answer 38

RBC breakdown

Question 39

polycythemia

Answer 39

high RBCs

Question 40

anemia

Answer 40

low RBC

Question 41

hemoglobin in kidney

Answer 41

nephrotoxic -damages renal tubule cells Tx dialysis

Question 42

red pulp

Answer 42

of spleen -RBC graveyard as age - get more rigid heme > bilirubin Fe recycled

Question 43

Hg breakdown

Answer 43

macrophage -porphyrin ring broken down by heme oxidase give biliverdin and CO

Question 44

methemoglobin

Answer 44

Hg carrying ferric iron - Fe3+ loses ability to carry oxygen methemoglobin reductase - solves problem - metHg back to normal Hg

Question 45

caboxyhemoglobin

Answer 45

Hg bound to CO

Question 46

phenacetin

Answer 46

or sulfonamides leads to sulfhemoglobin

Question 47

HgA2

Answer 47

2 alpha and 2 delta

Question 48

HgF

Answer 48

2 alpha and 2 gamma fetal

Question 49

sickle cell trait

Answer 49

heterozygote HgS

Question 50

sickle cell disease

Answer 50

homozygote HgS

Question 51

point mutation in globin chain

Answer 51

sickle cell disease

Question 52

inherited defect in regulation of globin chain synthesis

Answer 52

thalassemia -underproduced globin production

Question 53

microcytic hypochromic anemia

Answer 53

thalassemia has prominent target cells on peripheral smear decreased MCV and MCH

Question 54

Hg H disease

Answer 54

loss of 3 of 4 alpha globin genes

Question 55

alpha-thalassemia major

Answer 55

loss of all 4 alpha globin genes hydrops fetalis Hg barts forms

Question 56

cooleys anemia

Answer 56

beta thalassemia major

Question 57

beta thalassemia

Answer 57

protection against malaria

Question 58

hair on end skull radiograph

Answer 58

beta thalassemia