|
CYP isoenzymes
# = found in lung tissue | |||||||
| CYP2 10 subfamilies, 15 genes, 8 pseudogenes
(drug and steroid metabolism) - about 20% of liver CYP! | |||||||
| Isoenzyme | Substrates | Inducer | Inhibitor | Alleles | Effects (alleles, interactions) | ||
| CYP2A6 (about 4% of liver CYP) | nicotine,
7-hydroxylates coumarins | ? | ? | *1 .. *5 (and variants) | *2 : inactive (1-3% of Caucasians) *4 : inactive *5 : inactive (deletions common in Asians) | ||
| CYP2A13 | (found in nasal mucosa) | ? | ? | ? | ? | ||
| CYP2B6 # | artemisinin, S-mephobarbital, S-ifosfamide cyclophosphamide coumarin activation! | phenobarbital, cyclophosphamide | ? | ? | {used in retroviral vector gene Rx of cancer!}
expression in early childhood is poor | ||
| CYP2C8 # | TCA, diazepam (found in kidney, adrenal, brain, uterus, breast, ovary & duodenum), verapamil | rifampicin, phenobarbitone {despite lacking a 'Barbie box' : J Biochem Mol Toxicol 1999;13(6):289-95 } | cimetidine | -?- |
expression in early childhood is poor | ||
| CYP2C9 |
S-warfarin,
phenytoin,
diclofenac & other NSAIDS,
tolbutamide, fluoxetine, torsemide, verapamil ,
dextromethorphan
losartan (activated) | rifampicin, ? carbamazepine, ? ethanol | fluconazole, ketoconazole, sulphonamides (sulfaphenazole),
sulphinpyrazone, amiodarone, ritonavir, metronidazole
{cimetidine has a minimal effect} | *1 .. *3 | *2, *3 : less active. phenytoin toxicity | ||
| CYP2C18 # | (found in brain, uterus, breast, kidney & duodenum; liver levels ~10% of those of 2C8 and 2C9) | Similar to 2C19; metabolises cyclophosphamide, ifosfamide , verapamil , lansoprazole | |||||
| Isoenzyme | Substrates | Inducer | Inhibitor | Alleles | Effects | ||
| CYP2C19 |
(found in duodenum but few other extrahepatic tissues;
lower hepatic expression than 2C9)
(S) mephenytoin, phenytoin,
diazepam, TCA (clomipramine, imipramine..),
dextromethorphan,
propranolol, omeprazole, progesterone,
sertraline,
aminopyrine
meprobamate formation from carisoprodol, proguanil ? (activated) | phenobarbitone, artemisinin (?) | sulfaphenazole, fluoxetine, omeprazole, ritonavir, fluvoxamine, oral contraceptives ticlopidine | *1, *2 .. *8 | *2 .. *8 : inactive
(in up to 20% of Asians {*2 and *3},
3% of Caucasians, 19% of African
Americans, 8% of Africans, up to 71% of Pacific islanders
)
Low activity allows dual Rx of H pylori with good success!
Low B12 with long term omeprazole Rx!
risk of phenytoin toxicity (?) | ||
| CYP2D6 "debrisoquine hydroxylase" (about 2% of liver CYP, the only active 2D in man {rats have ~six!} ) found mainly in the liver, with LITTLE intestinal activity | debrisoquine, dextromethorphan, beta blockers, haloperidol, chlorpromazine, thioridazine dexfenfluramine, flecainide, propafenone, mexiletine, procainamide fentanyl, pethidine {=meperidine}, SSRIs (fluoxetine), TCAs, trazadone, zuclopenthixol, S-mianserin, tolterodine; azelastine , tramadol, codeine, | NOT INDUCIBLE; (? does activity increase in pregnancy) | cimetidine { >>> ranitidine },
quini[di]ne, methadone, SSRIs,
| *1A .. *1E, *1XN, *2A, *2B .. *2K, *2XN, *3 .. *8, *9, *10, *11 .. *16, *17, *18, *19, *20, *21 .. *32, *33, *34, *35, *35X2, *36, *37, *38. |
*10 (common in Chinese); *17 (common in Black Africans); ~10% of Caucasians are poor metabolisers; X = multiple copies (Ethiopian);
[
increased activity, normal activity,
decreased activity, no activity,
others unknown ]
| ||
| Isoenzyme | Substrates | Inducer | Inhibitor | Alleles | Effects | ||
| CYP2E1 # (about 7% of liver CYP) | paracetamol {=acetaminophen},
pentobarbitone, tolbutamide, propranolol, rifampicin coumarin activation! | chronic ethanol intake, isoniazid, benzene | disulfiram, (cimetidine) (acute ethanol intake!) | *1A .. 1C, *1D, *2, *3, *4, *5 .. *7 | *1D : (increased), *2 : decreased ? association with alcoholic liver disease, liver cancer, lung & nasopharyngeal cancer (cigarettes) (Chinese polymorphism) Noteworthy drug interactions | ||
| CYP2G1 (olfactory epithelium) | a steroid hydroxylase | ? | ? | ? | {may mediate olfactory toxicity of 2,6 dichlorobenzonitrile, and acetaminophen, at least in mice} | ||
| CYP2J2 | Probably catalyses formation of epoxyeicosatrienoic acids (EETs), which modulate bronchial and vascular tone, ion transport and peptide hormone secretion! Found in gut (epithelial, endothelial, smooth muscle and autonomic ganglion cells), and widespread in human lung | ||||||
| CYP2R1 | ? | ||||||
| CYP2S1 | ? | ||||||
| Last update 2000-1-22 | Author jo@anaesthetist.com |