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Flashcards in Heme Catabolism Deck (11):
1

Explain how free plasma Hb and heme are toxic to vascular endothelium.

Heme iron --> oxidative stress --> endothelial activation --> vasoocclusive events and thrombus formation

Free Hb scavenges NO --> vasoconstriction; NO acts on smooth muscle cells to generate cGMP, signaling smooth muscle contraction

Imbalance can lead to severe vasoconstriction and hypertension

2

Explain how heme can lead to lipid peroxidation.

Heme is hydrophobic and can intercalate into lipid bilayers --> lipid peroxidation

Can lead to structural changes in membranes
Products form adducts/crosslinks with non lipids
Disrupt membrane dependent signaling

3

Where does extravascular hemolysis take place?

Within macrophages of spleen and liver ("tissue macrophages" = red pulp macrophages in spleen and Kupfer cells in liver)

4

What does intravascular hemolysis require to scavenge hemoglobin-haptoglobin complexes?

CD163 positive marcrophages

5

What is haptoglobin?

Acute-phase glycoprotein
Binds free Hb
Produced by hepatocytes and secreted into blood
Levels increased with inflammation and neplastic disease
Marker for hemolysis
"Antioxidant" after release into plasma --> oxy-Hb dimers bind haptoglobin tightly and sequester oxy-Hb preventing free heme and oxidative damage of heme iron

6

What happens when haptoglobin's buffering capacity is overwhelmed?

Hb undergoes rapid conversion to metHb, liberating heme
Heme than binds Hemopexin

7

What is Hemopexin?

Acute phase glycoprotein
Binds free heme
Produced by hepatocytes and secreted in blood
Levels increased with inflammation and in response to inflammatory cytokines and during heme overload

8

What does haptoglobin bind? What does hemopexin bind?

Haptoglobin binds free Hb
Hemopexin binds free Heme

9

What receptor does the Haptoglobin:Hb complex bind on macrophages? What about the Hemopexin:heme complex?

Haptoglobin:Hb binds CD163 on macrophages
Hemopexin:heme binds CD91 on macrophages

**Both are a part of intravascular hemolysis

10

Where is the enzyme HO-1 located?

In the ER with active site facing the cytoplasm

11

What causes jaundice/scleral icterus?

Accumulation of elevated bilirubin in skin and sclera