Heme Catabolism Flashcards Preview

Heme/Lymph > Heme Catabolism > Flashcards

Flashcards in Heme Catabolism Deck (21):
1

What are the 2 goals of heme catabolism?

1)handle the hydrophobic products of porphyrin ring cleavage
2)retain, safely mobilize & reuse iron

2

What 2 reactions can heme/Fe2+ perform under oxidative stress?

Fe2+ can generate ROS and cause lipid peroxidation
Heme is hydrophobic and can intercalate into lipid bilayers

3

What are the effects of lipid peroxidation?

structural changes in membranes
adduct/crosslink formation with non lipids
disruptions in membrane dependent signaling

4

What molecule does free hemoglobin scavenge?

NO, if too much is bound vasoconstriction can occur...leads to HTN

5

Which route of hemolysis is hte major route?

extravascular

6

Types of macrophages

extravascular: tissue macrophages of red pulp of spleen and kupfer cells in liver
intravascular: CD163 positive macrophages that scavenge hemoglobin-haptoglobin complex

7

Haptoglobin features

glycoprotein that binds free Hb
produced by liver in hepatocytes
levels increase during inflammation and neoplastic disease

8

What happens to haptoglobin during hemolysis?

levels decrease

9

Can haptoglobin-hemoglobin pass through glomerular filter?

No, this helps conserve iron

10

What happens when haptoglobin is overwhelmed?

Hb converts to metHb which liberates heme
ferriheme binds albumin and other things where it is transferred to hemopexin

11

Hemopexin features

glycoprotein that binds free heme
produced by liver
increased levels during heme overload

12

What receptor binds the hemopexin-heme complex?

CD91 scavenger receptor

13

Once heme is taken up by a macrophage what happens?

globin protein is degraded in lysosome
heme is transferred to cytosol and catabolized by heme oxygenase 1 (HO-1)

14

What occurs with the accumulation of bilirubin?

jaundice or icterus

15

What do inherited disorders of bilirubin metabolism lead to?

hyperbilirubinemia

16

What color is bilirubin?

orange

17

How is heme ring opened in macrophage?

1)ring is cleaved by HO-1 this requires electrons from CYPOR
2)oxidation by molecular oxygen with elimination of CO and release of iron, resulting in biliverdin

18

What color is biliverdin?

green

19

How is biliverdin converted to bilirubin?

by biliverdin reductase

20

What happens to bilirubin that crosses into the bloodstream?

it is bound to albumin

21

Where is bilirubin taken up, stored, conjugated and excreted?

the liver