141
reactions is to excrete out the foreign chemicals by increasing their hydrophilicity
to a larger extent.
Glucuronidation Glucuronidation plays a major role in the biotransformation of
xenobiotics in almost all mammals. Glucuronidation requires the cofactor uridine
diphosphate-glucuronic acid (UDP glucuronic acid), and the reaction is catalysed by
UDP glucuronosyl transferases (UGTs), localized in the endoplasmic reticulum of
the liver and other tissues, such as the kidney, intestine, skin, brain, spleen and nasal
mucosa. The site of glucuronidation is generally an electron-rich nucleophilic heteroatom (O, N or S) (Fig. 5.5). Therefore, substrates for glucuronidation contain such
functional groups as aliphatic alcohols and phenols (which form O-glucuronide
ethers), carboxylic acids (which form O-glucuronide esters), primary and secondary
aromatic and aliphatic amines (which form N-glucuronides), and free sulfhydryl
groups (which form S-glucuronides). Coumarin and certain other carbonyl- containing
compounds are glucuronidated to form arylenol-glucuronides. Other than xenobiotFig. 5.5 Conjugation with glucuronic acid (glucuronidation)
5 Biotransformation Enzymes
reactions is to excrete out the foreign chemicals by increasing their hydrophilicity
to a larger extent.
Glucuronidation Glucuronidation plays a major role in the biotransformation of
xenobiotics in almost all mammals. Glucuronidation requires the cofactor uridine
diphosphate-glucuronic acid (UDP glucuronic acid), and the reaction is catalysed by
UDP glucuronosyl transferases (UGTs), localized in the endoplasmic reticulum of
the liver and other tissues, such as the kidney, intestine, skin, brain, spleen and nasal
mucosa. The site of glucuronidation is generally an electron-rich nucleophilic heteroatom (O, N or S) (Fig. 5.5). Therefore, substrates for glucuronidation contain such
functional groups as aliphatic alcohols and phenols (which form O-glucuronide
ethers), carboxylic acids (which form O-glucuronide esters), primary and secondary
aromatic and aliphatic amines (which form N-glucuronides), and free sulfhydryl
groups (which form S-glucuronides). Coumarin and certain other carbonyl- containing
compounds are glucuronidated to form arylenol-glucuronides. Other than xenobiotFig. 5.5 Conjugation with glucuronic acid (glucuronidation)
5 Biotransformation Enzymes