120914 heme catabolism Flashcards
what can Fe2+ do? and heme?
ferrous iron can generate ROS (Fenton rxn) and cause lipid peroxidation
heme is hydrophobic and can intercalate into lipid bilayers
heme iron’s effects on vasculature?
promotes oxidative stress that can cause endothelial activation, causing vasooclusive events and thrombus formation
what can free hemoglobin do?
scavenge NO, reducing its bioavailability
what is the major path of degradation of senescent RBC?
extravascular hemolysis–within macrophages of spleen and liver
in intravascular hemolysis, what happens to hemoglobin?
requires CD163 positive macrophages to scavenge hemoglobin-haptoglobin complex
what is haptoglobin
acute phase glycoprotein that binds free Hb
clinical marker of hemolysis (its levels decrease in hemolysis)
how does haptoglobin-hemoglobin complex conserve iron?
b/c it doesn’t pass through glomerular filter
intravascularly, if there is overwhelming Hb, what happens?
heme is released
hemopexin
binds free heme in vasculature
acute phase glycoprotein
hemopexin-heme complex binds to CD91 scavenger receptor, which is expressed on numerous cell types
what happens to heme in a cell?
transferred to cytosol where it is catabolized by heme oxygenase 1 (HO-1), which is associated with ER
where are senescent RBCs degraded?
mostly by macrophages of reticuloendothelial system of liver and spleen
heme ring opening step
first step:
catalyzed by heme oxygenase (HO-1), which works on ferroprotoporphyrin IX ring
second step:
produces CO
iron is realeased
resulting green pigment is BILIVERDIN
what happens to Fe2+ formed from opening of heme ring?
bound by ferritin in cytosol
what enzymes catalyzes converson of biliverdin to bilirubin?
biliverdin reductase in the cytosol
which is less polar: biliverdin or bilirubin?
bilirubin (corsses membranes more easily)
