Fig. 3

Correlation of transcript abundance and metabolic activity for major drug metabolizing enzymes in human and minipig liver. Liver mRNA abundance of all major phase I and II drug metabolizing enzymes was determined with minipig and human microarray data (left panel). Metabolite formation rates (pmol/min/mg protein) were determined for phase I and II enzyme substrates for human and minipig primary hepatocyte suspension cultures (right panel). Transcript abundance and metabolic activities of human and minipig major cytochrome p450 enzymes (CYPs), aldoketoreductases (AKR/CR), aldehyde oxidase (AOX), N-acetyltransferases (NATs), and sulfotransferases (SULT) are shown as black dots. UDP-glucuronosyltransferase (UGT) family members are shown as red dots, UGT1A1 as separate blue dots, and flavin-monooxygenase 1 (FMO1) as green dots. Liver mRNA expression levels show higher expression for FMO1, UGTs, SULT1C4, and SULT1E1 in minipig as compared to human. The UGT family expression data is represented by four subtypes detected by isoform specific probes. All major phase I CYPs show very similar expression levels in both species. Higher UGT, AKR, and FMO1 enzyme activities compare well with higher liver gene expression levels in minipig. Bars present average transcript abundance and metabolic activity