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[Biochemistry](https://durgical.com/en/biochemistry/) · Topic

# Glucuronidation

The most important phase II conjugation: UGT enzymes attach glucuronic acid to drugs, bilirubin and hormones so they can be excreted.

Updated 2026-11-01

## Key facts

- Substrate + UDP-glucuronic acid → glucuronide + UDP; catalysed by UDP-glucuronosyltransferases (UGT1A and UGT2B).
- UDP-glucuronic acid comes from UDP-glucose via UDP-glucose dehydrogenase (with NAD⁺).
- UGTs sit in the lumen of the endoplasmic reticulum, mainly in hepatocytes, gut and kidney.
- Substrates: bilirubin (UGT1A1), acetaminophen, morphine, irinotecan's SN-38, oestrogens, thyroid hormones, bile acids.

## In detail

- Glucose from glycogen or diet is activated as UDP-glucose.
- UDP-glucose dehydrogenase oxidises it (two NAD⁺) to UDP-glucuronic acid.
- UGT transfers the glucuronic acid to an –OH, –COOH, –NH₂ or –SH group of the substrate.
- The glucuronide is large, negatively charged and soluble: MRP2 carries it into bile, or MRP3 into blood and urine.
- In the gut, bacterial β-glucuronidase can release the drug and send it back into circulation (enterohepatic cycle).

## Clinical notes

- Gilbert (UGT1A1*28) and Crigler-Najjar: unconjugated hyperbilirubinaemia from low glucuronidation.
- Severe irinotecan diarrhoea comes from SN-38 that UGT1A1 conjugates poorly or that gut β-glucuronidase releases.
- Morphine-6-glucuronide is active and accumulates in kidney failure: more sedation.
- In acetaminophen overdose glucuronidation and sulfation saturate, leaving more drug to form NAPQI.

## Pathways

- [Heme breakdown and bilirubin](https://durgical.com/en/biochemistry/pathways/heme-breakdown-and-bilirubin/)

## Related conditions

- [Gilbert syndrome](https://durgical.com/en/conditions/gilbert-syndrome/)
- [Crigler-Najjar syndrome](https://durgical.com/en/conditions/crigler-najjar-syndrome/)
- [Neonatal jaundice](https://durgical.com/en/conditions/neonatal-jaundice/)
- [Acetaminophen toxicity](https://durgical.com/en/conditions/acetaminophen-toxicity/)

## Related

- [UGT1A1 (bilirubin UDP-glucuronosyltransferase)](https://durgical.com/en/biochemistry/enzymes/ugt1a1/)
- [UDP-glucose](https://durgical.com/en/biochemistry/molecules/udp-glucose/)
- [Bilirubin](https://durgical.com/en/biochemistry/molecules/bilirubin/)
- [Xenobiotic biotransformation: phases I, II and III](https://durgical.com/en/biochemistry/topics/xenobiotic-biotransformation-phases-i-ii-and-iii/)
- [Acetaminophen metabolism and NAPQI](https://durgical.com/en/biochemistry/topics/acetaminophen-metabolism-and-napqi/)
- [Glycogen metabolism](https://durgical.com/en/biochemistry/pathways/glycogen-metabolism/)

## Test yourself

Think of the answer, then tap the question to see it.

## What is the activated co-substrate of glucuronidation and where does it come from?

UDP-glucuronic acid, formed by oxidising UDP-glucose with NAD⁺.

## Why is irinotecan more toxic in people with Gilbert syndrome?

Its active metabolite SN-38 is cleared by UGT1A1, which has low activity in Gilbert syndrome.

## What is the enterohepatic circulation of a glucuronide?

Gut β-glucuronidase releases the drug, which is reabsorbed and returns to the liver.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Glucuronidation](https://reactome.org/PathwayBrowser/#/R-HSA-156588) (Reactome, 2026); [Phase II - Conjugation of compounds](https://reactome.org/PathwayBrowser/#/R-HSA-156580) (Reactome, 2026); [What is pharmacogenomics?: MedlinePlus Genetics](https://medlineplus.gov/genetics/understanding/genomicresearch/pharmacogenomics/) (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).

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