Cofactors, substrates, inhibitors, and primary tissue locations for additional drug-metabolizing enzymes
| Enzyme | Cofactor | Examples of Substrates | Examples of Inhibitors | Tissue Location |
|---|---|---|---|---|
| FMO (FMO1, FMO3, FMO5) | NADPH | Benzydamine, clozapine, imipramine, tamoxifen, nicotine, voriconazole, sulindac sulfide | Methimazole | Kidney, intestine, fetal liver (FMO1); liver, lung, kidney (FMO3); liver (FMO5) |
| AO | Molybdenum pyanopterin | Allopurinol, citalopram carbazeran, tamoxifen metabolites | Hydralazine, chlorpromazine, isovanillin | Liver, lung, kidney, small intestine |
| XO | Molybdenum pyanopterin | 1-Methylxanthine, allopurinol | FYX-051, febuxostat | Liver, heart, lung, adipose, mammary gland |
| MAO (MAO-A, MAO-B) | FAD | 5-Hydroxytryptamine and epinephrine (MAO-A); benzylamine and β-phenylethylamine (MAO-B) | Moclobemide, clorgyline (MAO-A) | Liver, placenta, brain |
| Sertraline and clomipramine (both) | Deprenyl (MAO-B) | |||
| CES | None | Cocaine, methylphenidate, meperidine | Benzil, trifluoromethyl ketones, organophosphorus compounds | Liver |
| Epoxide hydrolase (sEH and mEH) | None | Carbamazepine and styrene oxide (mEH); epoxyeicosatrienoic acids (sEH) | 1,1,1-Trichloropropylene oxide (mEH) | Liver |
| Valproic acid | ||||
| Aldo-ketoreductase (multiple isoforms) | NADPH | Haloperidol, ketotifen, oracin | NSAIDs | Liver, kidney, brain, blood |
| Sulfotransferase (multiple isoforms) | PAPS | Acetaminophen and troglitazone (1A1); salbutamol and dobutamine (1A3); ethynylestradiol (1E1); budenoside (2A1) | Pentachlorophenol | Liver, intestine, platelets, brain, kidney, endometrium, skin, prostate, placenta |
| glutathione transferase (multiple isoforms) | Glutathione | 1-Chloro-2,4-dinitrobenzene, chlorambucil, melphalan | Ethacrynic acid, piriprost, indomethacin | Liver, kidney, lung, brain, skeletal muscle, heart, small intestine, spleen |
| N-Acetyltransferase (NAT1, NAT2) | Acetyl CoA | p-Aminobenzoic acid and p-aminophenol (NAT1); dapsone, sulfamethazine, procainamide (NAT2) | Acetaminophen, 5-iodosalicylic acid | Liver, esophagus, small intestine, stomach, colon, bladder, lung |
| Acyl-CoA synthetase | ATP, CoA | Ibuprofen, flunoxaprofen, clofibrate | Triacsin C, rosiglitazone | Liver, heart, adipose tissue |
| Methyltransferase (structure-dependent isoforms) | S-Adenosyl methionine | 6-Mercaptopurine, 6-thioguanine, azathioprine, dopamine, captopril | Entacapone, tolcapone | Liver (adult and fetal), lung, kidney, small intestine |
FAD, flavin adenine dinucleotide; FYX-051, 4-(5-pyridin-4-yl-1H-[1,2,4]triazol-3-yl)pyridine-2-carbonitrile; mEH, microsomal epoxide hydrolase; NAT, N-acetyltransferase; NSAID, nonsteroidal anti-inflammatory drug; PAPS, 3′-phosphoadenosine-5′-phosphosulfate; sEH, soluble epoxide hydrolase.