Uridine diphosphate glucuronide

Scheme 1.6 Uridine diphosphate glucuronide transferase cycle. (Reproduced by permission of the Royal Society of Chemistry.)...

O-glucuronidation is catalysed by glucuronyl transferase that transfers a glucuronic acid moiety from uridine diphosphate glucuronide to an alcohol, phenol or carboxylic acid group (Fig. 8.36). This is the most important... 

Figure 8.36 Glucuronidation of a hydroxylated compound by UDP-glucuronyl transferase with uridine diphosphate glucuronide (UDPG) as the co-factor.

Iyer L, King CD, Whitington PF et al. Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes. J Clin Invest 1998 101 847-854. 

UDPG was the first of a whole new class of nucleotides, in which the uridine diphosphate group is attached to a monosaccharide. Two important members of the class are uridine diphosphate glucuronic acid, the intermediate in the synthesis of glucuronides and of many other compounds, and uridine diphosphate N-acetylglucosamine which is an intermediate in the synthesis of mucopolysaccharides. Uridine diphosphate muramic acid was isolated by Park (P2) from Staphylococcus aureus... 

Nicotine glucmonidation results in an N-quatemary glucmonide in humans (Benowitz et al. 1994). This reaction is catalyzed by uridine diphosphate-glucuronosyltransferase (UGT) enzyme(s) producing (5)-nicotine-N-P-glucmonide. About 3-5% of nicotine is converted to nicotine glucuronide and excreted in urine in humans. 

Uridine diphosphate glucuronosyltransferase, more specifically UGTIAI, is capable of glucuronidating bilirubin. The clinically relevant polymorphisms related to genetic abnormalities in the UGTIAI enzyme are those associated with familial... 

The other primary Phase II metabolic pathway is glucuronidation, which involves the formation ofglucuronic acid conjugates of xenobiotics. This is catalyzed by a family of UDP-glucuronosyl transferases (UGTs) in the presence of uridine diphosphate... 

It has now been established that in common with many other glu-curonides, bilirubin glucuronide can be synthesized in the adult rat, rabbit, mouse, and guinea pig liver by the enzymatic transfer of glucuronic acid from uridine diphosphate glucuronic acid to an acceptor substance, namely, bilirubin (Fig. 3) (B17, G5, L3, L5, S8). The transferring enzyme (glucuronyl transferase) has been shown by Schmid et al. 

Jin C, Miners JO, Lillywhite KG, et al. Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs. J Pharmacol Exp Ther 1993 264... 

Fig. 4 Formation of uridine diphosphate glucuronic acid (UDP-GA) and its conjugation with clofibric acid. Inversion takes place during conjugation, the a-D-glucuronic acid forming a P-D-glucuronide. At a more alkaline pH, such glu-curonides may undergo intramolecular rearrangement to forms resistant to enzymic hydrolysis by P-glucuronidase.

Polycyclic aromatic amines are readily absorbed into the body via the gastrointestinal tract, where metabolic activation takes place. Aryl amines are N-hydroxylated and subsequently glucuronidated via uridine diphosphate (UDP)-glucuronosyl transferase or sulfated by sulfotransferases, N-acetylation of the amine, and 0-acetylation of the N-hydroxy amine can occur. 

---