TABLE 1.
Inhibition of hSULT2A1-catalyzed sulfation of DHEA by metabolites of tamoxifen
The sulfation of DHEA was determined using 0.03 μg of purified hSULT2A1 in the presence of varied concentrations of inhibitor and either 1 μM DHEA (for IC50 values) or 0.22–1.0 μM DHEA for determination of the mechanism of inhibition and related kinetic constants. The data are expressed as mean ± S.E. from three independent experiments. Calculation of kcat values was based on 33,678 as the subunit molecular mass of hSULT2A1.
| Metabolite |
IC50 |
Type of Inhibition |
Vmax |
Km |
kcat/Km |
Ki |
|---|---|---|---|---|---|---|
| nmol/min per mg | μM | min−1μM−1 | μM | |||
| Endoxifen | 1.7 ± 0.4 | Noncompetitive | 243 ± 17 | 0.7 ± 0.1 | 10.9 | 2.8 ± 0.2 |
| N-desTAM | 8.3 ± 2.6 | Competitive | 260 ± 24 | 0.8 ± 0.1 | 11.0 | 17.2 ± 2.0 |
| 4-OHTAM | 10.0 ± 1.0 | Noncompetitive | 178 ± 7 | 0.5 ± 0.1 | 11.8 | 19.4 ± 1.6 |
| TAM-NO | 11.1 ± 1.1 | Noncompetitive | 592 ± 75 | 3.5 ± 0.5 | 5.7 | 9.6 ± 0.2 |