13 Heme Catabolism

Question 0

Haptoglobin

Answer 0

Molecule that scavenges free hemoglobin dimers and facilitates Red pulp macrophage and Kupfer cell phagocytosis via CD163 receptor.

Blocks glomerular filtration
ACUTE PHASE LIVER PROTEIN

HP2 genotype (alpha2Beta) homozygous associated with CHD and inflammation

Question 1

Why do we need special mechanisms for heme catabolism

Answer 1

1)FE 2+ can be oxidized by oxygen to yield ferric iron and superoxide- ROS in cells
Lipid peroxidation–> Endothelial dysfunction
2) Free Hb scavenges NO- and decreases its availability, decreasing its function as a vasorelaxant

Question 2

Hemopexin

Answer 2

Molecule that scavenges free heme and facilitates red pulp macrophage and kupfer cell phagocytosis Via LRP1 receptor

Acute phase liver protein

Also carries HEME in the cytosol until it is catabolized by Heme oxygenase 1

Question 3

HO-1

Answer 3

STEP 1
Heme oxygenase decyclizes the ring using O2, NADPH, and a CYP450OR, this results in
GREEN BILIVERDIN, CO, AND FE2+

CO is taken up by hemoglobin,
FE2+ is scavanged by ferritin

Question 4

Biliverdin Reductase

Answer 4

STEP 2

Green Biliverdin is reduced to ORANGE bilirubin with the help of NADH or NADPH

Question 5

Bilirubin transport

Answer 5

Bilirubin binds albumin in the plasma, then is taken up by the liver and excreted