Three steps from heme to bilirubin diglucuronide, which is water soluble
Route: Heme b → Biliverdin IXα → Bilirubin IXα → Bilirubin diglucuronide
Heme oxygenase opens the heme ring at one methine bridge, the alpha bridge. That carbon leaves as carbon monoxide, the iron is released as Fe²⁺, and the product is the green, linear pigment biliverdin IXα. The reaction uses three O₂ and electrons from NADPH, which reach the enzyme through NADPH-cytochrome P450 reductase. Biliverdin reductase then reduces the central methine bridge of biliverdin with NADPH, and the product is the orange-yellow bilirubin IXα. The colors of a healing bruise follow these two steps. UDP-glucuronosyltransferase 1A1 moves glucuronate from UDP-glucuronate onto the carboxyl groups of the two propionate side chains of bilirubin, as ester links, one at a time, and releases UDP. Bilirubin is insoluble in water. The product, bilirubin diglucuronide, is water soluble, and this lets the liver excrete it into bile. Gilbert syndrome (a mild loss of activity of this enzyme) and Crigler-Najjar syndromes 2 (a strong loss) and 1 (no activity) raise the level of unconjugated bilirubin in blood and can cause jaundice. The structure shown is the UDP-glucuronate binding half of a related glucuronosyltransferase, 2B7, because the PDB holds no entry for 1A1. What happens to bilirubin diglucuronide in the gut is left out here.
Practice this pathway All pathways
| Step | Enzyme | EC | In | Out |
|---|---|---|---|---|
| 1 | Heme oxygenase 1 | 1.14.14.18 | O₂, O₂, O₂, NADPH, NADPH, NADPH | CO, Fe²⁺, H₂O, H₂O, H₂O, NADP⁺, NADP⁺, NADP⁺ |
| 2 | Biliverdin reductase A | 1.3.1.24 | NADPH | NADP⁺ |
| 3 | UDP-glucuronosyltransferase | 2.4.1.17 | UDP-glucuronate, UDP-glucuronate | UDP, UDP |
Build any of these from its atoms.
Enzyme names and EC numbers are those used on the interactive board. Checked against sources: see the claim table in the repository (tools/pathway_data/checks).