Methylation of quercetin and fisetin, flavonoids widely distributed in edible vegetables, fruits and wine, by human liver

The aim of this investigation was to study the methylation of quercetin and fisetin, 2 chemically related flavonoids, in human liver and to this purpose, an assay was set-up to measure the rates of quercetin and fisetin methylation in human liver. The methylation rates (pmol/min/mg) of quercetin and fisetin were measured in 10 liver samples and the mean ± SD and the median were 170 ± 30 and 177 (quercetin) and 183 ± 15 and 178 (fisetin). The rates of quercetin and fisetin methylation were not different (p = 0.283). The fold of variation among samples was 2 (quercetin) and 1.3 (fisetin). Methyltransferase towards quercetin and fisetin followed Michaelis-Menten kinetics, and the K_m values were 2.6 ± 0.3 (quercetin) and 8.6 ± 0.7 μM (fisetin, p = 0.009) and the V_max values were 187 ± 20 (quercetin) and 276 ± 33 pmol/min/mg (fisetin, p = 0.009). Two, 4 and 8 μl of red Chianti wine added to the incubation mixture reduced the rate of quercetin methylation to 75 ± 4%, 65 ± 9% and 59 ± 9%, respectively, and that of fisetin methylation to 62 ± 3%, 51 ± 3% and 44 ± 4%, respectively. In conclusion, quercetin and fisetin are methylated in human liver and their rates of methylation have a limited variation among subjects.