Lecture 4

tetra-pyrolic structure with an iron atom in the center (but iron always in Fe2+ or ferrous state)

synthesized in mitochondria and transported to cytosol to combine with globin

each molecule bonds one O2 molecule (basically Fe2+ binds with O2)

4

4 O2 or 1.34 mL oxygen

polypeptide synthesized thru expression of globin gene

4 globin chain

helical structure (helices A-H) each heme sits on crevice formed by E and F helices, binds F8 and E7 histidine residues

cytoplasm of erythroid precursors to make full Hb molecule

quaternary structure
4 polypeptide chains

α1β1 α2β2
α1β2 α2β1

α1β1 α2β2

stability of quaternary structure in oxy and deoxy forms

globular

2α chains, 2b chains, 4 hemes, 4 O2 molecules

1.34 mL per Hb molecule

chr 16

chromosome 11

gene transcription, translation, globin synthesis in erythroid precursors (not in mature RBC)

Protoporphyrinogen IX with protoporphyrinogen oxidase becomes protoporphyrin IX
protoporphyrin IX becomes heme with incorporation of Fe2+ using enzyme ferrochelatase

heme and globin

Hgb A, Hgb A2, Hgb F

intrauterine Hgb
Hgb at birth
abnormal Hgb

Gower-1
Gower-2
Portland
Hgb F

Hgb F and Hgb A

H and Bart's

α2 β2

α2 δ2
alpha 2 delta 2

α2 γ2
alpha 2 gamma 2

c2 γ2

c2 epsilon6

α2 epsilon2

β4

γ4

oxygen delivery and carbon dioxide delivery

binds, transports, and unloads oxygen

carbonic acid and chloride shift

~ 27 mm Hg, 50% saturation, P50

P50 < 27 mm Hg;
HIGHER Oxygen affinity

P50 > 27 mm Hg
LOWER oxygen affinity

body temp
2,3 BPG levels
pH, altitude, hypoxia
abnormal Hgb
myoglobin
fetal hemoglobin

decreased temp
decreased 2,3 DPG
decreased [H+]
CO

increased temp
increased 2,3 DPG
increased [H+]

Hgb O2 affinity is INVERSLY related to both acidity and to the concentration of CO2

decreased H+ ions
increased pH
increased O2 affinity

increased H+ ions
decreased pH
decreased O2 affinity

exchange of HCO3- with Cl-
in exchange for HCO3 (diffused outside) one Cl- ion will be shifted inward

animal food; absorption more efficient

vegetables; absorption less efficient

acidic foods (like citrus)

oxalates, phytates, phosphates, and calcium

must be converted to ferric form

reacts with ferroportin in membranes to prevent iron from exiting these cells into the blood

Fe3+ (ferric) is reduced to Fe2+ before transport across luminal membrane of the enterocyte by ferrireductase, duodenal cytochrome b (Dcytb)

able to be transported through luminal membrane into the enterocyte cytoplasm by divalent metal transporter 1 (DMT1)

absorbed iron as heme

iron is removed from heme by heme oxygenase-1 (HO-1)

some iron may be stored as ferritin, most is chaperoned to the opposite membrane and carried into the blood by ferroportin

becomes reoxidized by Hephaestion as it exits for transport in the blood by transferrin (Tf)

protein of hepatic origin that inhibits ferroportin from transporting iron out of the enterocyte

Hepcidin

1. body iron levels increase, liver detects it
2. increase hepcidin and secreted into blood where it travels to iron-regulating cells, enterocytes, mq, and hepatocytes
3. Hepcidin reacts with ferroportin in their membranes and prevent iron from exiting cells into blood
4. Body iron declines, living decreases Hepcidin
5. ferroportin in membranes will be active and transport iron into plasma
6. repeat

liver

binds to and carries Fe3+ to the erythropoietic cells
has 2 binding sites for iron (binds 2 irons) before iron is bound it is called apotransferrin

ferritin and hemosiderin

Fe3+ atoms are stored in cage like protein called apoferritin, once iron is bound → ferritin

cytoplasm for mitochondria of cells

degraded form of ferritin and metabolically less available

available transport iron

highest in the morning (fasting! Recommended)

iron deficiency anemia

indirect indicator of transferrin level

indicator of iron stores

ferritin = APR, serum level will increase in acute inflammation / infections
will make ferritin measurement for body iron storage study less reliable in these conditions

acute phase reactant

cells regulate the amt of transferrin receptor (TfR) on their membrane based on intracellular iron;
serum iron low, TfR increase
soluble form of TfR (sTfR) is measurable

sTfR will increase in cases of low serum iron (ex. Iron deficiency anemia)

protoporphyrin IX which is not bound to iron (due to lack of iron) and therefore is free inside the RBCs

in iron deficiency, FEP will increase

due to lack of iron, protoporphyrin IX will find zinc and bind to it;
increases in iron deficiency