Conversion of five proluciferin esters by human cytochrome P450 enzymes

Abstract

Background Probe substrates are an important tool for activity monitoring of human drug metabolizing enzymes such as cytochromes P450 (CYPs). Brief Methods In the present study we have tested human CYPs for metabolization of five proluciferin ester substrates which had previously only been known to be hydroxylated by CYP26A1. Major Results It was found that these substrates were converted by another 21 human CYPs, which belong to the CYP families 1 to 4, 7, and 26. Thus, 66 new pairs of enzyme and substrate were identified. Correlation analysis indicated the presence of three distinct sets of enzymes with high similarity in their activity profiles that encompass a total of 16 individual enzymes. Conclusions Some of these newly identified correlations may serve as a starting point for further study of those human CYPs whose activities are not yet satisfactorily understood.

Mutual Influence of Human Cytochrome P450 Enzymes and UDP-Glucuronosyltransferases on Their Respective Activities in Recombinant Fission Yeast

“…Therefore, it was the aim of the present study to determine the effect of co-expression of each one of the 19 human members of the UGT families 1 and 2 on the activity of three human CYPs. In this way, two of the most important drug metabolizing CYPs (CYP2C9 and CYP2D6) could be tested with CYP4Z1 as an internal control (as it is not known to have a function in xenobiotic biotransformation, and many of the marketed and in-house synthesized luciferin probe substrates are metabolized by this enzyme [23][24][25][26], which makes it a reliable control for bioluminescent assay in CYP metabolism).…”

Design and engineering of logic genetic-enzymatic gates based on the activity of the human CYP2C9 enzyme in permeabilized Saccharomyces cerevisiae cells

“…Thus, P450s are important for maintaining homeostasis and metabolising drugs [ 12 ]. Human cytochrome P450s have been expressed in S. pombe for long time [ [13] , [14] , [15] , [16] , [17] , [18] ]. In particular, the permeabilized fission yeast system known as enzyme bags is a very efficient platform to scrutinize all human P450s against any potential candidate drug in a quick time [ 13 , 19 ].…”