Heme Degradation: From Heme to Bilirubin
Heme from senescent red blood cells is degraded primarily in the reticuloendothelial system (spleen and liver).
| Step | Enzyme/Process | Key Transformation |
|---|---|---|
| Step 1 | Heme Oxygenase | Opens the heme ring to produce biliverdin (green pigment), CO, and Fe2+. |
| Step 2 | Biliverdin Reductase | Reduces biliverdin to unconjugated bilirubin (yellow pigment). |
| Transport | Albumin | Unconjugated bilirubin is insoluble; it travels bound to albumin to the liver. |
| Conjugation | UDP-glucuronosyltransferase | Conjugates bilirubin with glucuronic acid to increase water solubility. |
High-Yield Core Realities:
- Unconjugated vs. Conjugated: Unconjugated bilirubin is toxic (lipid-soluble) and can cause kernicterus in neonates. Conjugated bilirubin is non-toxic and water-soluble, excreted into bile.
- Clinical Significance: Elevated unconjugated bilirubin suggests pre-hepatic (hemolysis) or hepatic causes (Gilbert syndrome). Elevated conjugated bilirubin suggests obstructive (biliary) or hepatobiliary pathology.
- Enterohepatic Cycling: Bacteria in the intestine convert conjugated bilirubin into urobilinogen, which is either excreted in feces as stercobilin or reabsorbed and excreted in urine as urobilin.