Catabolism of heme is the process by which the heme molecule is broken down into simpler compounds.
This process primarily occurs in the liver and spleen and involves several key steps:
1) Heme Oxygenase (HO):
Reaction: Heme is broken down into biliverdin, carbon monoxide (CO), and free ferrous iron (Fe²⁺).
Enzyme: Heme oxygenase (HO).
Cofactors: Utilizes molecular oxygen and NADPH.
Mechanism: HO adds oxygen to the heme, cleaving the heme ring and releasing biliverdin, CO, and Fe²⁺.
2) Biliverdin Reductase (BVR):
Reaction: Biliverdin is reduced to bilirubin.
Enzyme: Biliverdin reductase (BVR).
Cofactors: Uses NADPH.
Mechanism: BVR reduces biliverdin to bilirubin by adding hydrogen atoms.
3) Conjugation of Bilirubin:
Process: In the liver, bilirubin is made more water-soluble by conjugation with glucuronic acid.
Enzyme: Uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1).
Product: Bilirubin diglucuronide.
Mechanism: UGT1A1 attaches glucuronic acid molecules to bilirubin, making it easier to excrete.
4) Excretion and Metabolism of Bilirubin:
Process: Conjugated bilirubin is excreted into bile and travels to the intestine.
Intestinal Metabolism: Gut bacteria convert bilirubin into urobilinogens.
Fate of Urobilinogens: Some are oxidized to stercobilins (excreted in feces), while others are reabsorbed and excreted as urobilins in urine.
