TABLE 2.

Kinetic Analyses of O-glucuronidation of the trans Isomers of 4-OH-TAM and Endoxifen by UGT Variants^a

	trans-4-OH-TAM			trans-Endoxifen
UGT Variant	V_max (pmol min⁻¹ μg⁻¹)^b	K_M (μM)	V_max/K_M (μl min⁻¹ −g⁻¹)^b	V_max (pmol min⁻¹ μg⁻¹)^b	K_m (μM)	V_max/K_M (μl min⁻¹ μg⁻¹)^b
UGT2B7^268His	0.55 ± 0.18	3.7 ± 0.6	0.15 ± 0.03	3.0 ± 0.44	101 ± 17	0.03 ± 0.004
UGT2B7^268Tyr	0.54 ± 0.09^*	8.7 ± 0.8^**	0.062 ± 0.01^**	0.55 ± 0.01^**	101 ± 15	0.006 ± 0.001^**
UGT1A10^139Glu	4.7 ± 0.3	96 ± 8	0.05 ± 0.006	5.7 ± 0.7	40 ± 3	0.14 ± 0.005
UGT1A10^139Lys	2.1 ± 0.2^**	52 ± 6^**	0.04 ± 0.006	1.9 ± 0.2^**	13 ± 2^**	0.14 ± 0.004
UGT1A8^{173Ala/277Cys}	2.3 ± 0.1	23 ± 2	0.10 ± 0.02	5.4 ± 0.2	98 ± 9	0.06 ± 0.004
UGT1A8^{173Gly/277Cys}	5.4 ± 0.2^**	43 ± 7^**	0.13 ± 0.03	5.9 ± 0.4	135 ± 26	0.04 ± 0.005^*
UGT1A8^{173Ala/277Tyr}	no detectable activity			no detectable activity

All data are the mean ±SD based on three independent experiments. Homogenates from cells overexpressing UGT1A8^{173Ala/277Tyr} exhibited no detectable activity against trans-4-OH-TAM and trans-endoxifen.

Data are expressed per μg UGT protein as determined by Western blot analysis.

P = 0.05;

^**

P < 0.01.