Recombinant systems expressing human cytochrome P450 isoforms (rCYP) are used in vitro for rapid screening for metabolic activity as well as for in vitro in vivo extrapolations (IVIVE) [1]. However, abundances of the respective enzymes in human liver are needed to correct for the relative contribution of each enzyme to the total metabolism. Shimada et al. (1994) is the most cited source for the latter information [914 citations in ISI database (September, 2003)] despite the fact that the study was based on liver samples from only 30 Japanese and 30 Caucasian subjects [2]. Therefore, the aim of our study was to derive abundance values for individual CYPs using all available data (19 sources). Two electronic data bases MEDLINE and BIDS EMBASE, and personal files (1990-2003) containing references from Current Contents and Reference Update were searched for the pertinent literature using appropriate key words. Authors were contacted directly when further information was required. Only human liver data from Caucasians were included and the source was identified to ensure that none were duplicated in the analyses. For each isoform, abundance values were tested for homogeneity and shape of the distribution. Following calculation of the weighted mean, standard deviation and coefficient of variation (CV) [3], the geometric mean (GM) and the geometric standard deviation were derived assuming a log-normal distribution [4]. Table Abundance of CYPs (pmol P450 mg-1 protein) in human liver determined from a meta-analysis of all reported data and those cited by by Shimada et al (1994).
Abundances derived for each of the isoforms in this study and those reported by Shimada et al. [2] are shown in the table. With the exception of CYP1A2 and CYP2D6, mean values from the meta-analysis appear to be greater. The values reported in our study are based on 42 to 241 liver samples and therefore may give a more realistic representation of CYP abundance and its variability in the Caucasian population than those reported [2] and cited frequently by many research groups. In view of the possible differences between Japanese and Caucasians [2] a meta-analysis similar to the one presented here is warranted to derive abundance values for the Japanese population and possibly other ethnic groups. 1. Proctor NJ, et
al. Xenobiotica (in press). |