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.

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).

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.

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.

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

Sources: Glucuronidation (Reactome, 2026); Phase II - Conjugation of compounds (Reactome, 2026); What is pharmacogenomics?: MedlinePlus Genetics (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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Representative model, for educational purposes only.