TABLE 2

Rates of 4MU, 1NP, naproxen, TFP, and LTG glucuronidation activities by UGT1A1, UGT1A1(H39P), UGT1A6, UGT1A6(H38P), UGT1A9, UGT1A9(H37P), and UGT1A4

Data are means of duplicate estimates (<10% variance).



Rate of Glucuronide Formation
UGT Enzyme or Mutant 4MU
1NP
Naproxena
TFP
LTG

Lowb
Highb
Lowb
Highb
Lowb
Highb
40 μM
100 μM
1500 μM
3000 μM
pmol/min · mg
1A1 89 178 89 167 3 8 N.A. N.A. N.A. N.A.
1A1 (H39P) 11 24 N.A. 13 N.A. N.A. 89 121 21 30
1A6 31360 53710 4820 7030 75 95 N.A. N.A. N.A. N.A.
1A6 (H38P) N.A. N.A. N.A. N.A. N.A. N.A. N.A. N.A. 5 6
1A9 7970 16240 48 98 42 106 N.A. N.A. N.A. N.A.
1A9 (H37P) N.A. N.A. N.A. 190 N.A. N.A. N.A. N.A. 162 298
1A4
N.A.
N.A.
N.A.
N.A.
N.A.
N.A.
521
733
125
202
  • N.A., no activity detected.

  • a Acyl glucuronidation pathway.

  • b “Low” concentration corresponds to approximate Km or S50 values: 4MU, 100 μM for UGT1A1 and UGT1A6 and 10 μM for UGT1A9; 1NP, 300 μM for UGT1A1, 3 μM for UGT1A6, and 1 μM for UGT1A9; naproxen, 1000 μM for UGT1A1 and UGT1A9 and 800 μM for UGT1A6. &quot;High&quot; concentration is 5 times the low concentration.