Tissue-Specific mRNA Expression Profiles of Human Phase I Metabolizing Enzymes Except for Cytochrome P450 and Phase II Metabolizing Enzymes

Summary:Pairs of forward and reverse primers and TaqMan probes specific to each of 52 human phase I metabolizing enzymes (alcohol dehydrogenase, aldehyde dehydrogenase, aldehyde oxidase, dihydropyrimidine dehydrogenase, epoxide hydrolase, esterase, flavin­containing monooxygenase, monoamine oxidase, prostaglandin endoperoxide synthase, quinone oxidoreductase, and xanthene dehydrogenase) and 48 human phase II metabolizing enzymes (acetyltransferase, acyl­CoA:amino acid N­acyltransferase, UDP­glucuronosyltransferase, glutathione S­transferase, methyltransferase, and sulfotransferase) were prepared. The mRNA expression level of each target enzyme was analyzed in total RNA from single and pooled specimens of various human tissues (adrenal gland, bone marrow, brain, colon, heart, kidney, liver, lung, pancreas, peripheral leukocytes, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thymus, thyroid gland, trachea, and uterus) by real­time reverse transcription PCR usingan ABI PRISM 7700 Sequence Detection System. Further, individual differences in the mRNA expression of representative human phase I and II metabolizingenzymes in the liver were also evaluated. The mRNA expression profiles of the above phase I and phase II metabolizingenzymes in 23 different human tissues were used to identify the tissues exhibitinghigh transcriptional activity for these enzymes. These results are expected to be valuable in establishingdrugmetabolism­mediated screeningsystems for new chemical entities in new drugdevelopment and in research concerningthe clinical diagnosis of disease.