Glucuronidation

Intracellular metabolic reaction taking place mainly in the endoplasmic reticulum of the hepatocytes in which glucuronic acid is transferred to an endo- or exogenous substrate. The reaction is catalyzed by UDP-glucuronosyltransferases (UGT) of which several isoenzymes exist. Inhibition or induction of UGT can lead to drug interactions.

The UDP-glucuronosyltransferases will be divided into families and subfamilies:

• UGT1: family 1
• UGT1A: Subfamily A
• UGT1A1: Individual enzyme

The UDP-glucuronosyltransferases are located in the endoplasmic reticulum of cells, especially hepatocytes. UDP-glucuronosyltransferases are also found extrahepatic in various other organs.

Glucuronidation is catalysed by the enzyme UDP-glucuronosyltransferase (UGT). By splitting off the UDP at the C1 carbon atom of the UDP-glucuronic acid, glucuronic acid is connected to the substrate at C1 via a glycosidic bond. The process of glucuronidation takes place in the endoplasmic reticulum of the hepatocytes. The resulting glucuronides are significantly more hydrophilic than the initial substrates. This enables excretion via the kidney.

Drug substances: Glucuronidation is an important phase II metabolism (conjugation) for the metabolism of drugs, steroid hormones, glucocorticoids, bilirubin and other lipophilic substances (biotransformation). Numerous active pharmaceutical ingredients are glucuronidated, e.g. NSAIDs, paracetamol, steroid antiepileptics, paracetamol, opioids, estrogens: estradiol, ethinyl estradiol, tricyclic antidepressants, naloxone, benzodiazepines, lamotrigine, etc.

Drug interactions: Like cytochromes P450, UDP-glucuronosyltransferases can be inhibited and induced and thus cause interactions.

Examples of inhibitors are immunosuppressants. Examples of inducers are rifamycin, barbiturates and various other drugs. Antiepileptic drugs.