UDP glucuronyl transferase

UDP-Glucuronyl Transferase Ultrarapid Metabolizer Unstable Angina Unwanted Effects UPR... 

Morcillo, Y., Janer, G., and O Hara, S.C.M. et al. (2004). Interaction of tributyl tin with cytochrome P450 and UDP glucuronyl transferase systems of fish in vitro smdies. Environmental Toxicology and Chemistry 23, 990-996. 

Stevenson, D.E. and Hubl, U. (1999) Optimization of /3-D-glucuronide synthesis using UDP-glucuronyl transferase Enzyme and Microbial Technology 24, 388-396. 

Scheme 7. General glucuronidation reaction catalyzed by UDP-glucuronyl transferases.

Glucuronidation involves the transfer of D-glucuronic acid from UDP-a-glu-curonic acid to an acceptor compound. The family of enzymes which catalyze this reaction are the UDP-glucuronyl transferases [16]. The reaction proceeds by nucleophilic Sn2 substitution of the C-1 carbon of glucuronic acid, the product undergoing inversion of configuration. The mechanism is illustrated schematically in Figure 7.21. 

Bl. Bakken, A. F., Effects of unconjugated bilirubin on bilirubin-UDP-glucuronyl transferase activity in liver of newborn rats. Pediat. Res. 3, 205-209 (1969). 

B17. Black, M., Billing, B. H., and Heirwegh, K. P. M., Determination of bilirubin UDP-glucuronyl transferase activity in needle-biopsy specimens of human liver. Clin. Chim. Ada 29, 27-35 (1970). 

M13. Mowat, A. P., and Arias, I. M., Partial purification of hepatic UDP-glucuronyl-transferase and studies of some of its properties. BiocMm. Biophys. Acta 212, 65-78 (1970). 

Odifevre, M., and Luzeau, R., Measurement of the activity of bilirubin UDP-glucuronyl transferase. Application to needle biopsy specimens. Rev. Eur. Etud. Clin. Biol. 16, 84-85 (1971). 

V5. Vessey, D. A., and Zakim, D., Regulation of microsomal enzymes by phospholipids. IV. Species differences in the properties of microsomal UDP-glucuronyl-transferase. Biochim. Biophys. Acta 268, 61-69 (1972). 

W8. Winsnes, A., The effects of sulfhydryl reacting agents on hepatic UDP-glucuronyl-transferase in vitro. Biochim. Biophys, Acta 242, 649-559 (1971). 

Deliconstantinos G, Mykoniatis M, Papadimitriou D. 1986. Carbon tetrachloride modulates the rat hepatic microsomal UDP-glucuronyl transferase activity and membrane fluidity. Experientia 42 181-183. 

Cigarette smoke, administered intranasally to young male C57BL mice fed 5 and 100 ppm of vitamin E, 20 min/day for 8 weeks, produced no effect on UDP-glucuronyl-transferase . ... 

This is the most common single metabolic reaction undergone by drugs, which occurs in the liver. These reactions are catalyzed by a family of enzymes known as uridine diphosphate (UDP) glucuronyl transferases. These enzymes are present in liver, kidney, intestine and lungs. 

Commercially available black pepper comes from the entire unripe fruit of a Piper nigrum L. plant and is valued for its pungent taste and aroma. Besides its hot flavor, there are many folk medicine remedies using black pepper. It has antiallergic activity. Piperine strongly inhibits hepatic arylhydrocarbonhydroxylase and UDP-glucuronyl transferase activities. Some proven uses for black pepper extracts are as an insecticide and as a tumor inhibitor. To research claims such as these, it is necessary to isolate the components of pepper. 

Subsequent studies have shown (e.g. 5,6, Table I) that the liver of newborns is indeed deficient in enzymes needed not only for drug metabolism but also for the elimination of natural products. For example, because of the lack of UDP-glucuronyl transferase resulting in the inability to dispose of bilirubin, the newborn is at risk for brain damage by kernicterus. That PEP carboxykinase, the key catalyst of gluconeogenesis de novo is absent at 7 months and still at low titers 3 days after birth (Table I), probably contributes to the fact that transient hypoglycemia (which can also cause brain damage) represents a hazard to full term as well as premature infants. The immaturity of the hepatic enzyme composition imposes limitations on the choice of nutrients used to supplement or re-... 

Enzyme-catalysed glucuronidation is one of the most important detoxification mechanisms of the body. Of the various isoforms of the UDP-glucuronyl transferase family of enzymes, only one isoform, bihmbin-UDP-glucuronyl transferase UGT-1, is physiologically important in bihmbin glucuronidation. 

Gilbert s syndrome results from decreased levels of UDP-glucuronyl transferase. The defect is in the promoter region, the TATAA element, rather than the gene itself. Gilbert s syndrome results in a mild hyperbilirubinaemia, without any clinical sequelae. 

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