TABLE 3

Kinetic parameters of 4′-HPPH O-glucuronidation by recombinant human UGT enzymes Data are means ± S.D. (n = 3).

(S)-4′-HPPH O-Glucuronide Formation
(R)-4′-HPPH O-Glucuronide Formation
S50
Vmax
 Normalized Vmax
 CLmax
n
 S50
Vmax
 Normalized Vmax
 CLmax
n
μM pmol/min/mg pmol/min/unit nl/min/unit μM pmol/min/mg pmol/min/unit nl/min/unit
UGT1A1 Supersomes 81 ± 20 14 ± 1 1 ± 0 6 ± 1 1.4 ± 0.1 110 ± 27 179 ± 25 11 ± 2 55 ± 4 1.6 ± 0.3
UGT1A9 Supersomes 25 ± 1 38 ± 1 4 ± 0 91 ± 1 1.3 ± 0.0 33 ± 4 16 ± 1 2 ± 0 46 ± 3a 1.0 ± 0.1
UGT2B15 Supersomes 91 ± 12 504 ± 55 N.A. N.A. 1.7 ± 0.1 96 ± 6 121 ± 19 N.A. N.A. 2.2 ± 0.1
UGT1A1b 48 ± 5 9 ± 0 9 ± 0 23 ± 2 1.8 ± 0.2 74 ± 12 110 ± 5 110 ± 5 194 ± 20 1.6 ± 0.2
UGT1A1/1A4b 49 ± 1 7 ± 0 12 ± 0** 30 ± 1** 1.8 ± 0.2 70 ± 5 86 ± 3 138 ± 5** 250 ± 6** 1.7 ± 0.2
UGT1A1/1A6b 66 ± 2* 3 ± 0 4 ± 0** 10 ± 1** 1.7 ± 0.4 91 ± 14 35 ± 4 56 ± 6** 81 ± 6** 1.6 ± 0.2
UGT1A9b 23 ± 2 9 ± 1 67 ± 9 382 ± 16 1.5 ± 0.1 56 ± 14 3 ± 0 22 ± 3 56 ± 7 1.5 ± 0.4
UGT1A4/1A9b 22 ± 2 12 ± 2 52 ± 8 296 ± 28† 1.7 ± 0.1 41 ± 6 4 ± 1 15 ± 2† 50 ± 11 1.6 ± 0.2
UGT1A6/1A9b
35 ± 5††
15 ± 1
50 ± 4†
192 ± 18††
1.5 ± 0.1
54 ± 8
4 ± 1
14 ± 2†
35 ± 2†
1.5 ± 0.2

  • N.A., not available.

  • ↵* P < 0.005.

  • ↵** P < 0.01, compared with single-expression system of UGT1A1 in HEK293 cells.

  • ↵† P < 0.005.

  • ↵†† P < 0.01, compared with single-expression system of UGT1A9 in HEK293 cells.

  • ↵ a The intrinsic clearance (Vmax/Km) was calculated, because the kinetics was fitted to Michaelis-Menten equation.

  • ↵ b HEK293 expression systems that were established in our previous studies (Fujiwara et al., 2007a,b).