Glucuronyl transferases induction

Apart from monooxygenases, other enzymes concerned wih xenobiotic metabolism may also be induced. Some examples are given in Table 2.5. Induction of glucuronyl transferases is a common response and is associated with phenobarbital-type induction of CYP family 2. Glutathione transferase induction is also associated with this. A variety of compounds, including epoxides such as stilbene oxide and... 

Emphasis is given to the critical role of metabolism, both detoxication and activation, in determining toxicity. The principal enzymes involved are described, including monooxygenases, esterases, epoxide hydrolases, glutathione-5 -transferases, and glucuronyl transferases. Attention is given to the influence of enzyme induction and enzyme inhibition on toxicity. 

RIFAMPICIN MYCOPHENOLATE Significant 1 plasma mycopheno-late concentrations (>60% with rifampicin) Attributed to induction of glucuronyl transferase Avoid co-administration... 

An inspiring, and likely the first, example for the therapeutic application of enzyme induction to affect the metabolic fate of an endogenous substance has recently been reported by Yaffe and his associates (71) phenobarbital treatment has been used to prevent hyperbilirubinemia by inducing the glucuronyl transferase, enhanced glucuronide formation enabled increased bilirubin excretion and resulted in decreased serum bilirubin concentration. 

Acetaminophen is metabolized mainly by liver glucuronyl transferase to form the inactive conjugate. A minor pathway (via P450) results in formation of a reactive metabolite (N-acetylbenzoquinoneimine) that is inactivated by glutathione (GSH). In overdose situations, the finite stores of GSH are depleted. Once this happens, the metabolite reacts with hepatocytes, causing nausea and vomiting, abdominal pain, and ultimately liver failure due to centrilobular necrosis. Chronic use of ethanol enhances liver toxicity via induction of P450. 

Nemoto, N., Takayama, S. 1980. Genetic differences between C57BL/6 and DBA/2 mice in the inductions of UDP-glucuronyl transferases for 3-hydroxybenzo(a)pyrene, p-nitrophenol, and bilirubin by 3-methylcholanthrene. Toxicol. Lett. 5(l) 45-50. 

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