Kinetic parameters (± S.E. of parameter fit) of EtG formation by pooled human liver, kidney, and intestinal microsomes, and recombinant UGTs
Results are the mean of duplicate experiments. Contributions of UGT to ethanol glucuronidation at the hepatic level were calculated using the RAF approach.
| Km | Apparent Vmaxa | Clinta | RAF | HLM Scaled Clint | Contribution to Overall Hepatic Microsomal Metabolism | |
|---|---|---|---|---|---|---|
| mM | pmol/mg/min | nl/mg/min | nl/mg/min | |||
| HLM | 1082 ± 343.3 | 757.9 ± 150.1 | 0.7004 | NA | ||
| HKM | 6224 ± 6843 | 1081 ± 1049 | 0.1736 | NA | ||
| HIM | 508.6 ± 102.7 | 28.34 ± 2.73 | 0.0550 | NA | ||
| UGT1A3 | 385.1 ± 106.7 | 10.71 ± 1.4 | 0.0278 | 0.31 | 0.0086 | 1.2% |
| UGT1A4 | 1706 ± 699.1 | 33.64 ± 9.6 | 0.0197 | 0.67 | 0.0132 | 1.9% |
| UGT1A7 | 193 ± 74.88 | 3.05 ± 0.41 | 0.0155 | ND | ||
| UGT1A8 | 312.1 ± 78.57 | 6.73 ± 0.68 | 0.0214 | ND | ||
| UGT1A9 | 501 ± 87.77 | 52.1 ± 4.43 | 0.1039 | 1.15 | 0.1196 | 17.1% |
| UGT2B7 | 619.7 ± 157.7 | 67.68 ± 8.97 | 0.1092 | 2.1 | 0.2293 | 32.7% |
| UGT2B4 | 442.1 ± 112.2 | 20.95 ± 2.41 | 0.0472 | ND | ||
| UGT2B15 | 203.1 ± 89.67 | 5.2 ± 0.81 | 0.0256 | ND | ||
| UGT2B17 | 132.9 ± 50.08 | 5.6 ± 0.66 | 0.0421 | ND |
EtG, ethyl glucuronide; Clint, intrinsic clearance; HIM, human intestinal microsomes; HKM, human kidney microsomes; HLM, human liver microsomes; Km, concentration of substrate required to produce 50% of Vmax; NA, not applicable; ND, not determined; RAF, relative activity factor; UGT, UDP-glucuronosyltransferase.
↵a Activities are not normalized to microsome or BD-Supersome UGT contents.