Table 4

Assigned and fitted parameters for the cellular kinetic model of E1S and E1 in zonal hepatocytes

V Embedded Image 4-a Maximum uptake velocity for E1S (nmol/min/106cells)2.92.9
K Embedded Image Michaelis-Menten constant for E1S uptake (μM)11.8 ± 0.910.3 ± 4.1
P Embedded Image 4-a Bidirectional uptake clearance for E1S (μl/min/106cells)4.04.0
P Embedded Image Bidirectional uptake clearance for E1 (μl/min/106cells)1484 ± 2421463 ± 149
V Embedded Image 4-b Maximum desulfation rate for E1S (nmol/min/106cells)2.21.9
K Embedded Image 4-b Michaelis-Menten constant for desulfation of E1S (μM)30.434.8
V Embedded Image Maximum sulfation rate for E1 (nmol/min/106cells)0.014 ± 0.015 0.077 ± 0.0524-150
K Embedded Image 4-c Michaelis-Menten constant for sulfation of E1 (μM)4.45.9
V Embedded Image 4-d Maximum metabolism rate for E1 (nmol/min/106cells)5.9 ± 2.0 9.4 ± 2.44-150
K Embedded Image 4-d Michaelis-Menten constant for metabolism of E1 to M (μM) 18 ± 3.0 19 ± 0.6
CL Embedded Image Excretion of E1S to intracellular vesicle (μl/min/106cells)0.66 ± 0.250.49 ± 0.23
nE1S4-e Number of binding sites for E1S1.51.5
k Embedded Image Binding association rate constant for E1S (l/min/μM/106cells)0.0014 ± 0.00010.0020 ± 0.0009
k Embedded Image 4-f Binding dissociation rate constant for E1S (l/min/106cells)0.0330.046
f Embedded Image Unbound fraction of intracellular E1 0.030 ± 0.0050.025 ± 0.004
f Embedded Image 4-g Unbound fraction of extracellular E1 0.840.84
Vc 4-h Cellular volume (ml/106 cells)0.00360.0041
Vec Extracellular volume (ml/106cells)0.99640.9959

Fitted values were obtained for each set of experiments, and data were expressed as mean ± SD; n = 5.

  • 4-150  Statistically different from parameter for periportal hepatocytes (ANOVA, P < 0.05).

  • 4-a  Obtained from Tan et al. (1999) and scaled up as described under Experimental Procedures.

  • 4-b  Scaled up from the desulfation rate constants for E1S, obtained from S9 of zonal hepatocytes.

  • 4-c  Constrained as V Embedded Image /CL Embedded Image .

  • 4-d  Glucuronidation, hydroxylation, and oxidation of E1 (other than sulfation of E1).

  • 4-e  Division of the effective binding concentration of E1S by the extracellular protein concentration.

  • 4-f  Constrained as k Embedded Image multiplied by K Embedded Image .

  • 4-g  Unbound fraction of E1 in the extracellular medium.

  • 4-h  Obtained fromGarcı̀a-Ruiz et al. (1994).