Drug-metabolizing enzymes UGTs

Table 4 Drug metabolizing enzyme (P450 isoforms (CYP), UDP-glucuronosyl transferase (UGT) and phenol sulfotransferase (PST)) substrates that can be used for the in situ measurement of activity in the human hepatocyte enzyme induction assay.

Individual drug metabolizing enzymes DMEs) like CYPs, FMOs, and UGTs are now routinely expressed, usually in insect cells using a baculovirus. Ultracentrifugation provides vesicles called microsomes, which contain these membrane-bound DMEs. One popular type of recombinant CYP preparation called Supersomes comes with CYP reductase, a necessary cofactor, co-expressed. Not only individual CYPs (2B6, 3A4, etc.) but also allelic variants like CYP2C9 2 are available for the study of possible pharmacogenomic effects on metabolism. 

Human CYPs involved in metabolism can be easily characterized because of the tools that are commercially available. However, similar tools are not available for other drug-metabolizing enzymes like FMOs, UGTs, and sulfotransferases. There are no specific inhibitors or monoclonal anitibodies identified for any of the commercially available expressed UGTs or sulfotransferases. Due to the lack of necessary tools it is difficult to quantitatively assess their contribution to the overall clearance of drugs that are metabolized by these enzymes. 

Although there are many enzymes involved in drug metabolism, the in vitro systems containing CYPs and UGTs are often used for metabolite synthesis due to the reasons discussed before. 

Drug Interactions. Phenobarbital is a potent enzyme inducer and may increase the elimination of any drug metabolized by CYP450-or UGT-mediated metabolism. Valproic acid, phenytoin, felbamate, cimetidine, and chloramphenicol inhibit phenobarbital metabolism, necessitating a decrease in dose. Ethanol increases the metabolism of phenobarbital. ... 

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