TABLE 2

Kinetic analysis of N-glucuronidation in UGT1A4- and UGT2B10-overexpressing cell homogenates and HLMs of TSNAs




TSNA

Vmax

KM

Vmax/KM

Normalized Vmax/KM UGT2B10/UGT1A4 Ratioa
pmol/min/mg total protein mM nl/min/mg total protein
UGT1A4 NNAL 99 ± 27b 22.79 ± 3.83 4.35 ± 0.96 Referent
NNN 182 ± 43 26.24 ± 14.27 7.70 ± 2.13 Referent
NAB 166 ± 22 5.37 ± 1.61 32.1 ± 6.63 Referent
NAT 124 ± 4 3.31 ± 0.23 37.6 ± 2.31 Referent
UGT2B10 NNAL 7.55 ± 0.37 3.62 ± 2.31 3.07 ± 2.13 3.0
NNN 7.66 ± 1.63 1.18 ± 0.27 6.60 ± 1.08 3.6
NAB 41.09 ± 11.28 0.28 ± 0.00 147 ± 42.0 19
NAT 52.65 ± 14.99 0.22 ± 0.06 242 ± 2.86 27
HLMc NNAL 259 ± 42 0.85 ± 0.42 348 ± 163
NNN 1400 ± 60 3.17 ± 0.37 446 ± 61
NAB 2476 ± 621 0.20 ± 0.03 12,806 ± 5069

NAT
2593 ± 457
0.16 ± 0.01
16,227 ± 2852

  • a Vmax/KM normalized by mRNA expression levels in UGT1A4- and UGT2B10-overexpressing HEK293 cell lines using GAPDH as an expression control

  • b Data are expressed as the mean ± S.D. of three independent experiments

  • c HLM from one individual