Kinetic parameters for the metabolism of 4-hydroxy-TAM to 3,4-dihydroxy-TAM and endoxifen in HLMs Average (apparent) formation rates vs. substrate concentrations were best fit to a single-site (3,4-dihydroxy-TAM and endoxifen in HG06 and HG93) or two-site binding (endoxifen in HG23 and HG112 and 3,4-dihydroxy-TAM in HG112) equations using a nonlinear regression analysis (see Data Analysis and Results). Kinetic parameters for the high affinity components (Vmax1, Km1, and Vmax1/Km1) are presented here.
HLMs | 3,4-Dihydroxy-TAM | Endoxifen | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Vmax | Km | Vmax/Km | Vmax | Km | Vmax/Km | |||||
| HG112 | 144 | 2.4 | 59.5 | 162 | 2.3 | 71.7 | ||||
| HG23 | ND | ND | ND | 77 | 6.5 | 11.8 | ||||
| HG06 | 41 | 3.1 | 13.2 | 68 | 8.7 | 7.8 | ||||
| HG93 | 27 | 6.4 | 4.1 | 67 | 14.9 | 4.5 | ||||
| Mean | 70.3 | 4.0 | 25.6 | 93 | 8.1 | 23.9 | ||||
| ±S.D. | 64.0 | 2.1 | 29.7 | 46 | 5.3 | 32.0 | ||||
Vmax, pmol/min/mg of protein; Km, μM; and Vmax/Km, μl/min/mg of protein.