Heme, Iron and Bilirubin Metabolism Flashcards
hemoglobin
heme - iron
globin - two pairs of chains
heme
porphrin ring with one iron chelated by 4 nitrogens
reversible oxygen attachment
heme synthesis
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
sideroblastic anemia
mutation of ALA synthase
porphyria
mutation in porphobilinogen synthase or PBG deaminase
Pb poisoning
affects ALA dehydratase
ALA synthase
rxn in mitochondria
ALA dehydratase
rxn in cytosol
ferrochelatase
rxn back into mitochondria
alpha globins
chromosome 16
beta globins
chromosome 11
thalassemia
disruption of balance of globin chain synthesis
Hb gower
embryonic
portland Hb
fetal
HbA
in adults
majority HbA
alpha2beta2
heme and globin
combine in cytoplasm
transferrin
carries iron
ferrous
Fe2+
Hg only binds
ferrous - Fe2+
ferrous bonds
4 - heme
1 - globin
1 - oxygen
iron absorption
duodenum
ferric
Fe3+
ferric reductase
DcytB
-Fe3+ to Fe2+
DMT1
cotransport Fe2+/H+ into cell
ferroportin
transport Fe2+ out of cell
regulated by hepcidin levels
hepicidin
regulator of ferroportin
-Fe transport out of cell
hemochromatosis
high levels of Fe
heme oxygenase
inside cells
-splits heme iron and releases free Fe3+
high Fe levels
high hepcidin
-decreased ferroportin
low Fe levels
low hepcidin
- increased ferroportin
- more absorption from gut
transport in blood
Fe3+ on transferrin
ferritin
storage of Fe
Fe + apoferritin
apoferritin
iron buffer system
HAMP mutation
decreased hepcidin
iron overload and hemochromatosis
RBC breakdown
120 days
-in spleen
no spleen - to liver
RBC metabolism
glycolysis - ATP and NADH
pentose phosphate - NADPH to maintain reduced glutathione
fava beans
RBC breakdown
polycythemia
high RBCs
anemia
low RBC
hemoglobin in kidney
nephrotoxic
-damages renal tubule cells
Tx dialysis
red pulp
of spleen
-RBC graveyard
as age - get more rigid
heme > bilirubin
Fe recycled
Hg breakdown
macrophage
-porphyrin ring broken down by heme oxidase
give biliverdin and CO
methemoglobin
Hg carrying ferric iron - Fe3+
loses ability to carry oxygen
methemoglobin reductase - solves problem - metHg back to normal Hg
caboxyhemoglobin
Hg bound to CO
phenacetin
or sulfonamides
leads to sulfhemoglobin
HgA2
2 alpha and 2 delta
HgF
2 alpha and 2 gamma
fetal
sickle cell trait
heterozygote
HgS
sickle cell disease
homozygote
HgS
point mutation in globin chain
sickle cell disease
inherited defect in regulation of globin chain synthesis
thalassemia
-underproduced globin production
microcytic hypochromic anemia
thalassemia
has prominent target cells on peripheral smear
decreased MCV and MCH
Hg H disease
loss of 3 of 4 alpha globin genes
alpha-thalassemia major
loss of all 4 alpha globin genes
hydrops fetalis
Hg barts forms
cooleys anemia
beta thalassemia major
beta thalassemia
protection against malaria
hair on end skull radiograph
beta thalassemia