UGTs uridine

There is a growing number of published examples of the utility of screening patients for pharmacogenetic markers prior to chemotherapy selection (1). Many published markers of association with chemotherapy outcome or toxicity still require validation in prospective studies. Examples of well-characterized pharmacogenetic markers include thiopurine methyltransferase (TPMT), UGT (uridine diphosphate [UDP]-glucuronosyltransferase) lAl, and epidermal growth factor receptor (EGER). 

Fig. (15). Metabolism of dietary flavonoids. GlcA = glucuronic acid UGT - uridine 5 -diphospoglucuronosyl transferase Met = methyl Sulf = sulfate COMT = catechol-O-methyl transferase PST = phenol sulfo transferase...

Figure 4 Fluxes and fates of chrysin (Chr) in the human enterocyte monolayer model Caco-2. G, glucuronide conjugate S, sulfate conjugate UGT, uridine diphosphate-glucuronosyltransferase SUIT, sulfotransferase.

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. 

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... 

Quercetin and other flavonols are subject to metabolic conversion during the absorption process in the small intestine. Phase II enzymes including uridine 5 -diphosphate glucuronosyl transferase (UGT), phenol-sulfotransferase (PST),... 

Typical reactions catalyzed by UGT enzymes require the cofactor uridine diphosphate-glucuronic acid, UDPGA. However, the C-terminus of all UGT enzymes contains a membrane-spanning domain that anchors the enzyme in the endoplasmic reticulum, and the enzyme faces the lumen of the endoplasmic reticulum, where it is ideally placed to conjugate lipophilic xenobiotics and their metabolites generated by oxidation, reduction, or hydrolysis. The lumenal... 

O Dwyer PJ, Catalano RB. Uridine diphosphate glucuronosyltransferase (UGT) lAl and irinotecan practical pharmacogenomics arrives in cancer therapy. J Clin Oncol 2006 24(28) 4534-8. 

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