TABLE 1

Kinetic parameters of FOSA N-glucuronide formation in liver microsomes from humans, rats, dogs, and monkeys and in recombinant hUGT2B4 and hUGT2B7

The kinetic parameters were derived from nonlinear regression analysis of the experimental data by fitting to a single-enzyme model or Hill equation. Each value represents best-fit values ± S.D. of triplicate points. Kinetic plots are presented in Fig. 2.




S 50 a

V max

CLmaxb

n a
μM pmol/min/mg protein μl/min/mg protein
Human 143 ± 6 732 ± 18 2.75 3.19 ± 0.42
Dog 195 ± 17 193 ± 12 0.50 2.46 ± 0.31
Monkey
189 ± 13
255 ± 14
0.70
2.73 ± 0.32

K m a
V max
CLintc

μM pmol/min/mg protein μl/min/mg protein
Rat 122 ± 9 355 ± 9 2.91
hUGT2B4 847 ± 122 88.8 ± 7.6 0.108
hUGT2B7
361 ± 32
1546 ± 71
4.33

  • a S50 and n (Hill coefficient) calculated by Hill equation; Km calculated by Michaelis-Menten equation.

  • b CLmax calculated as described under Material and Methods.

  • c CLint calculated as Vmax/Km.