[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Heme breakdown and bilirubin [Biochemistry](https://durgical.com/en/biochemistry/) · Metabolic pathway # Heme breakdown and bilirubin Heme from old red cells becomes bilirubin; the liver conjugates it and bile carries it to the gut, where it colours the stool. Updated 2026-11-01 ## Interactive map ## Key facts - About 250–350 mg of bilirubin is made per day; roughly 80 % comes from hemoglobin of old red cells removed by spleen macrophages. - Heme oxygenase opens the ring and releases CO (almost all the body's endogenous CO) and Fe²⁺, which is recycled. - Unconjugated (indirect) bilirubin is water-insoluble and travels bound to albumin; it does not appear in urine. - Liver UGT1A1 adds glucuronic acid (conjugated or direct bilirubin); MRP2 pumps it into bile, the slowest step. - Colonic bacteria turn it into urobilinogen: part is reabsorbed and leaves in urine as urobilin (yellow); the rest is oxidised to stercobilin (brown). **Also called** Heme catabolism ## Regulation - Heme oxygenase 1 is inducible: its substrate (heme), oxidative stress, hypoxia and inflammation switch it on. - Phenobarbital induces UGT1A1 (useful in Crigler-Najjar type 2). - Newborns have little UGT1A1 in the first days: the basis of physiological jaundice. ## The steps, one by one - **Step 1 · [Heme oxygenase (inducible HO-1, constitutive HO-2)](https://durgical.com/en/biochemistry/enzymes/heme-oxygenase/)** irreversible [Heme](https://durgical.com/en/biochemistry/molecules/heme/) + o2 + [NADPH](https://durgical.com/en/biochemistry/molecules/nadph/) → Biliverdin + Carbon monoxide (CO) + Ferrous iron (Fe²⁺) + nadp In the macrophage endoplasmic reticulum it breaks the heme ring: green biliverdin, CO and iron come out. **If it fails:** HO-1 deficiency is very rare: severe hemolysis, inflammation and endothelial damage. - **Step 2 · [Biliverdin reductase](https://durgical.com/en/biochemistry/enzymes/biliverdin-reductase/)** irreversible Biliverdin + [NADPH](https://durgical.com/en/biochemistry/molecules/nadph/) → [Bilirubin](https://durgical.com/en/biochemistry/molecules/bilirubin/) + nadp In the cytosol it reduces the central bridge of biliverdin, giving yellow bilirubin. **If it fails:** Its absence (very rare) leaves biliverdin unreduced: greenish skin and serum (green jaundice). - **Step 3 · [UDP-glucuronosyltransferase 1A1 (UGT1A1)](https://durgical.com/en/biochemistry/enzymes/ugt1a1/)** irreversible [Bilirubin](https://durgical.com/en/biochemistry/molecules/bilirubin/) + UDP-glucuronic acid → Bilirubin glucuronide (conjugated bilirubin) + UDP Bilirubin reaches the liver on albumin, enters the hepatocyte, and UGT1A1 attaches one or two glucuronic acids: it becomes water-soluble. **If it fails:** Activity down to ~30 %: Gilbert syndrome. Absent or nearly absent: Crigler-Najjar types 1 and 2. Immature: neonatal jaundice. [Crigler-Najjar syndrome →](https://durgical.com/en/conditions/crigler-najjar-syndrome/) - **Step 4 · MRP2 (ABCC2), canalicular transporter** irreversible Bilirubin glucuronide (conjugated bilirubin) + [ATP](https://durgical.com/en/biochemistry/molecules/atp/) → Conjugated bilirubin in bile + ADP + phosphate (Pi) It pumps conjugated bilirubin from the hepatocyte into the bile canaliculus using ATP; it is the rate-limiting step of the whole liver pathway. **If it fails:** Without MRP2: Dubin-Johnson syndrome (conjugated hyperbilirubinemia, black liver). When OATP1B1/1B3 reuptake fails: Rotor syndrome. [Dubin-Johnson syndrome →](https://durgical.com/en/conditions/dubin-johnson-syndrome/) - **Step 5 · Colonic bacterial β-glucuronidases and reductases** irreversible Conjugated bilirubin in bile → Urobilinogen In the gut, bacteria strip the glucuronide and reduce bilirubin to colourless urobilinogen; part returns to the liver (enterohepatic circulation). **If it fails:** In the newborn, the nearly sterile gut and mucosal β-glucuronidase send bilirubin back to the blood and add to jaundice. [Neonatal jaundice →](https://durgical.com/en/conditions/neonatal-jaundice/) - **Step 6 · Urobilinogen oxidation (colonic bacteria and kidney)** irreversible Urobilinogen → Stercobilin (stool) + Urobilin (urine) In the colon stercobilin forms and colours the stool; urobilinogen that reaches the kidney leaves as urobilin, the yellow of urine. **If it fails:** Pale stools and dark urine mean bilirubin is not reaching the gut: cholestasis or biliary obstruction. [Gallstones (cholelithiasis) →](https://durgical.com/en/conditions/gallstones/) ## Clinical notes - Overproduction (hemolysis) or failed uptake or conjugation: unconjugated hyperbilirubinemia, with no bilirubin in urine. - Failed excretion or biliary obstruction: conjugated hyperbilirubinemia, with dark urine and, if blocked, pale stools. - In complete biliary obstruction no bilirubin reaches the gut: urinary urobilinogen disappears. - The colour changes of a bruise (red-purple → green → yellow) show the pathway: heme → biliverdin → bilirubin. ## Related conditions - [Gilbert syndrome](https://durgical.com/en/conditions/gilbert-syndrome/) - [Crigler-Najjar syndrome](https://durgical.com/en/conditions/crigler-najjar-syndrome/) - [Dubin-Johnson syndrome](https://durgical.com/en/conditions/dubin-johnson-syndrome/) - [Rotor syndrome](https://durgical.com/en/conditions/rotor-syndrome/) - [Neonatal jaundice](https://durgical.com/en/conditions/neonatal-jaundice/) - [Sickle cell disease](https://durgical.com/en/conditions/sickle-cell-disease/) - [Gallstones (cholelithiasis)](https://durgical.com/en/conditions/gallstones/) - [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/) ## Related - [Heme oxygenase](https://durgical.com/en/biochemistry/enzymes/heme-oxygenase/) - [Biliverdin reductase](https://durgical.com/en/biochemistry/enzymes/biliverdin-reductase/) - [UGT1A1 (bilirubin UDP-glucuronosyltransferase)](https://durgical.com/en/biochemistry/enzymes/ugt1a1/) - [Heme](https://durgical.com/en/biochemistry/molecules/heme/) - [Bilirubin](https://durgical.com/en/biochemistry/molecules/bilirubin/) - [Hemoglobin and 2,3-BPG](https://durgical.com/en/biochemistry/enzymes/hemoglobin-and-2-3-bpg/) - [Heme synthesis](https://durgical.com/en/biochemistry/pathways/heme-synthesis/) - [Iron metabolism](https://durgical.com/en/biochemistry/topics/iron-metabolism/) - [Myoglobin](https://durgical.com/en/biochemistry/enzymes/myoglobin/) ## Test yourself Think of the answer, then tap the question to see it. ## Which enzyme opens the heme ring, and what does it release? Heme oxygenase: it releases biliverdin, carbon monoxide and Fe²⁺. ## Why does unconjugated bilirubin not appear in urine? It is water-insoluble and travels bound to albumin, which is not filtered by the glomerulus. ## What gives stool its brown colour? Stercobilin, which colonic bacteria form from urobilinogen. ## What is the slowest step in liver handling of bilirubin? Excretion of conjugated bilirubin into bile by MRP2; that is why liver disease usually raises the conjugated fraction. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/pathways/heme-breakdown-and-bilirubin/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Reactome | Heme degradation](https://reactome.org/PathwayBrowser/#/R-HSA-189483) (Reactome, 2026); [Bilirubin blood test: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/003479.htm) (MedlinePlus, US National Library of Medicine, 2026); [Jaundice | Icterus | MedlinePlus](https://medlineplus.gov/jaundice.html) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011). [← All of biochemistry](https://durgical.com/en/biochemistry/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/biochemistry/pathways/heme-breakdown-and-bilirubin/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/pathways/heme-breakdown-and-bilirubin/