Table 1

Kinetic parameters for SN-38 glucuronidation by WT and variant (G71R, P229Q, and Y486D) human UGT1A1s1-a

UGT1A1ApparentKmVmaxVmax/KmNormalizedVmax1-bNormalizedVmax/Km1-b
μM pmol/min/mg protein μl/min/mg protein pmol/min/mg protein μl/min/mg protein
WT11.5  ± 0.716.4  ± 4.01.40  ± 0.2616.4  ± 4.01.40  ± 0.26
G71R14.0  ± 0.43.7  ± 1.01-160 0.26  ± 0.071-160 9.2  ± 2.41-150 0.66  ± 0.171-160
P229Q18.0  ± 1.215.4  ± 3.20.86  ± 0.211-150 12.9  ± 2.70.73  ± 0.181-160
Y486D63.5  ± 7.81-160 1.9  ± 0.51-160 0.03  ± 0.011-160 4.2  ± 1.01-160 0.07  ± 0.021-160
  • 1-a  The results were expressed as the mean ± S.E.M. from three-independent transfection experiments. Asterisks signify data significantly different from that of WT at the following levels:

  • 1-150 p < 0.05;

  • 1-160 p < 0.01.

  • 1-b  Vmax values were normalized by the relative protein expression level, where the ratios for G71R, P229Q, and Y486D were 0.40, 1.2, and 0.45, respectively.