TABLE 2

Kinetic parameter estimates for MPAG formation by all reactive UGTs and their variant allozymes Determination of apparent Vmax and Km was performed for all UGTs for which MPAG formation was significant, namely, UGT1A1, UGT1A7, UGT1A8, UGT1A9, and UGT1A10, as well as for variant allozymes of UGT1A8 and UGT1A9. Sites of expression are: L, liver; K, kidney; GI, gastrointestinal tract; –, not expressed in L, K, or GI. Kinetic profiles are: H, hyperbolic; S, sigmoid.

UGT Source
Sites of Expression
n
Km
Absolute Vmax
RelativeaVmax
Clint
Kinetic Profile
μM pmol/min/mg pmol/min/mg μl/min/mg
1A1b L, GI – 185 ± 86 336 ± 37 24 ± 3 0.1 H
1A7b – – 30 ± 1 370 ± 7 23 ± 0.4 0.8 H
1A8 GI S
*1 1.7 298 ± 82 32,570 ± 5742 25,252 ± 4452 43
*2 (A 173G) 1.5 317 ± 69 26,858 ± 4760 24,461 ± 4335 41
*3 (C277Y) 1.3 118 ± 56 1864 ± 614 5371 ± 1771c 28
1A9 L, K, GI H
*1 291 ± 31 8380 ± 1506 8380 ± 1506 29
*2 (C3Y) 224 ± 32 9873 ± 2865 10,703 ± 3105 48
*3 (M33T) 720 ± 250c,d 4416 ± 500 11,888 ± 1346 17
1A10b
GI
–
119 ± 12
434 ± 37
10 ± 0.8
0.1
H

  • ↵ a For relative velocities, absolute rates were divided by UGT protein expression values assessed by Western blot using a polyclonal anti-UGT1A antibody as described under Materials and Methods

  • ↵ b Microsomes obtained from commercial sources

  • ↵ c p < 0.05 vs. *1

  • ↵ d p < 0.05 vs. *2