PHASE II DRUG METABOLIZING ENZYMES

Petra Jancova,Eva Anzenbacherova,Pavel Anzenbacher

doi:10.5507/bp.2010.017

Abstract

Phase II biotransformation reactions (also 'conjugation reactions') generally serve as a detoxifying step in drug metabolism. Phase II drug metabolising enzymes are mainly transferases. This review covers the major phase II enzymes: UDP-glucuronosyltransferases, sulfotransferases, N-acetyltransferases, glutathione S-transferases and methyltransferases (mainly thiopurine S-methyl transferase and catechol O-methyl transferase). The focus is on the presence of various forms, on tissue and cellular distribution, on the respective substrates, on genetic polymorphism and finally on the interspecies differences in these enzymes. A literature search using the following databases PubMed, Science Direct and EBSCO for the years, 1969-2010. Phase II drug metabolizing enzymes play an important role in biotransformation of endogenous compounds and xenobiotics to more easily excretable forms as well as in the metabolic inactivation of pharmacologically active compounds. Reduced metabolising capacity of Phase II enzymes can lead to toxic effects of clinically used drugs. Gene polymorphism/ lack of these enzymes may often play a role in several forms of cancer.

Highlights

It is generally accepted that the biotransformation of substances foreign to the body including drugs is divided into phases I and II
The cytochromes P450 constitute a superfamily of heme enzymes responsible for the metabolism of xenobiotics and endobiotics
The level of CATECHOL O-METHYL TRANSFERASE (COMT) enzyme activity is genetically polymorphic in human red blood cells and liver. This polymorphism is due to a G-to-A transition at codon 158 or codon 108 of the COMT gene and results in the substitution of the amino acid valine for methionine causing a decrease in the activity level of the COMT enzyme 3 to 4 fold[131]

Summary

Background

Phase II biotransformation reactions ( ‘conjugation reactions’) generally serve as a detoxifying step in drug metabolism. Phase II drug metabolising enzymes are mainly transferases. This review covers the major phase II enzymes: UDP-glucuronosyltransferases, sulfotransferases, N-acetyltransferases, glutathione S-transferases and methyltransferases (mainly thiopurine S-methyl transferase and catechol O-methyl transferase). The focus is on the presence of various forms, on tissue and cellular distribution, on the respective substrates, on genetic polymorphism and on the interspecies differences in these enzymes

Conclusions

INTRODUCTION

CONCLUSION