Table 1.
Compound | Metabolite identified in mammals9,16 | Mammalian CYP450 required for metabolite production | Metabolite recovered in supernatant (ng/ml) | Metabolite recovered in pellet (ng/ml) | Evidence that this reaction can occur in C. elegans |
---|---|---|---|---|---|
Phenacetin | Paracetamol | CYP1A2 | 5 | 14 | yes |
Tolbutamide | Hydroxytolbutamide | CYP2C8/9/19 | 1387 | 276 | yes |
Carboxytolbutamide | CYP2C8/9/19 | 4.5 | 1 | yes | |
Diclofenac | Hydroxydiclofenac | CYP2C9 | 67 | 667 | yes |
Amitriptyline | Nortriptyline | CYP2C19 | 207 | not tested | yes |
E-10-hydroxyamitriptyline | CYP2D6 | 40 | not tested | yes | |
Clomipramine | Norclomipramine | CYP2C19 | 230 | 1969 | yes |
Dextromethorphan | Dextrorphan | CYP2D6 | 1842 | 1251 | yes |
3-methoxymorphinan | CYP3A4 | 228 | 250 | yes | |
Nifedipine | Oxidised nifedipine | CYP3A4 | 692 | 10725* | yes |
We started with 50 µg/ml parent compound in 50 ml flasks over 48 h. Metabolite concentration was then measured after the 50 ml culture had been allowed to settle and concentration was measured by LCMS both in the worm pellet and in the supernatant. The concentration of metabolites produced is expressed in ng/ml. *As this value falls outside the linear calibration range of the experiment (see Methods), it should be taken only to confirm substantial production of the metabolite rather than a precise measure of quantity.