TABLE 1

Rates of glucuronidation by human liver microsomes

Rates for each substrate were determined as described under Materials and Methods and are the average of duplicate determinations, except in the case of nicotine and cotinine, where rates are the average of two independent experiments each carried out in duplicate. All duplicate values varied by less than 10%.

Sample
Substrates
PNP a
 Nicotine b
 Cotinine b
 Imipramine c
 Propofol c
109 34 d 406 558 — e —
123 32 d N.D. f N.D. 115 N.D.
126 75 146 140 109 25
127 42 d 326 467 338 77
129 59,35 d 212 325 260 160
130 53 154 191 218 75
132 89 184 231 273 170
133 77 348 388 209 48
134 31 d 347 545 420 173
2 53 673 869 — —
3 48 616 908 — —
5 48 207 239 — —
6 47 324 469 — —
10 95 432 748 — —
12
48
367
523
—
—

  • ↵ a Rates (nmol/min/mg protein) were determined with 0.5 mM PNP and 5 mM UDPGA.

  • ↵ b Rates (pmol/min/ml) were determined at pH 7.1 with 5 mM [3H]nicotine (3 nCi/nmol) and 10 mM UDPGA or 5 mM continine with 10 mM [14C]UDPGA (1 nCi/nmol).

  • ↵ c Imipramine, 1 mM, and propofol, 1 mM, glucuronidation rates (pmol/min/mg) were determined with 2 mM UDPGA or 2 mM [14C]UDPGA (4 nCi/nmol), respectively.

  • ↵ d Rates were determined with a different preparation of alamethicin from that used for other determinations.

  • ↵ e —, not determined.

  • ↵ f N.D., not detected; limit of detection: nicotine, 50 pmol/min/mg protein; cotinine, 100 pmol/min/mg protein; imipramine, 50 pmol/min/mg protein; and propofol, 20 pmol/min/mg protein.