P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature

Nelson, David R.; Koymans, Luc; Kamataki, Tetsuya; Stegeman, John J.; Feyereisen, René; Waxman, David J.; Waterman, Michael R.; Gotoh, Osamu; Coon, Minor J.; Estabrook, Ron W.; Gunsalus, I. C.; Nebert, Daniel W.

doi:10.1097/00008571-199602000-00002

Cited by 2,553 publications

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“…The enzyme system, which is located on the membrane of the endoplasmic reticulum, is widely found throughout the animal and plant kingdoms [16]. In humans it exists in the liver and some extrahepatic tissues such as gastro-intestinal tract, kidney and brain [17] and is designated by the letters CYP [18]. It is further subdivided into families of enzymes, which are characterised by numerals [19].…”

Section: Discussionmentioning

confidence: 99%

The effect of smoking on postoperative nausea and vomiting

Chimbira

Sweeney

2000

Anaesthesia

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SummaryIn an attempt to quantify the postoperative effects of smoking, 327 consecutive patients undergoing arthroscopic day case knee surgery were given a standard anaesthetic consisting of an intravenous induction with propofol and fentanyl followed by inhalational maintenance using isoflurane in an oxygen and nitrous oxide mixture. Pre-operatively, patients were asked inter alia to give details of social smoking habits. Postoperatively, patients were given standard analgesic and anti-emetic drugs. Prior to discharge patients were asked to give details of postoperative nausea and vomiting together with details of the severity of postoperative pain. There were 85 smokers and 242 nonsmokers. Of the 327 patients, a total of 42 (13%) complained of postoperative nausea and vomiting. Of the smokers, only 6% complained of postoperative nausea and vomiting in contrast to 15% of the nonsmokers (p , 0.05). It is postulated that enzyme induction is the most likely reason for this anti-emetic effect. Possible ways in which this clinically beneficial mechanism can be utilised to improve outcome after anaesthesia are discussed.

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Section: Discussionmentioning

confidence: 99%

The effect of smoking on postoperative nausea and vomiting

Chimbira

Sweeney

2000

Anaesthesia

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“…Studies with hepatic P450s have shown that P450-catalysed drug metabolism and the regulation of the expression of these xenobiotic-metabolizing enzymes can sometimes be quite different in humans compared with that found in experimental animals (Guengerich, 1989;Wrighton and Stevens, 1992;Nelson et al, 1996). In some cases, different strains within the same species may show differences in the levels of expression of specific P450s (Kraner et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Modulation of P450-dependent ifosfamide pharmacokinetics: a better understanding of drug activation in vivo

Brain

Yu²,

Gustafsson³

et al. 1998

Br J Cancer

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Summary The anti-cancer prodrug ifosfamide (IF) is metabolized by liver P450 enzymes by two alternative pathways. IF is activated to 4-hydroxy IF (4-OH-IF), which ultimately yields the alkylating mustard isophosphoramide, whereas IF N-dechlororethylation inactivates the drug and produces the neurotoxic metabolite chloroacetaldehyde (CA). Both reactions are catalysed by multiple liver P450 enzymes in vitro in isolated rat liver microsomes. The present pharmacokinetic study investigates the potential for modulation of these alternative pathways of IF metabolism in vivo using the adult male Fischer 344 rat model. Rats were treated with IF alone or in conjunction with various P450 inducers and inhibitors in an effort to improve the balance between drug activation and drug inactivation. Plasma concentrations, areas under the curve (AUC) and half-lives were calculated for 4-OH-IF and CA, allowing estimations of the extent of IF activation and deactivation/toxification. Induction of liver P450 2B enzymes by 4-day high-dose phenobarbital (PB) pretreatment significantly decreased the fraction of IF undergoing 4-hydroxylation (AUC4 OH -1 AUC4-OH IF+AUCCA), from 37% to 22% of total metabolism (P < 0.05), consistent with in vitro findings that the PBinducible P450 enzyme 2B1 plays a major role in IF N-dechloroethylation. Pretreatment with the P450 3A inducer dexamethasone proportionally decreased the AUC for both IF metabolites, without any net impact on the fraction of IF undergoing metabolic activation. By contrast, the P450 2B1 inhibitor metyrapone preferentially increased the AUC for the 4-hydroxylation pathway in 3-day low-dose PB-induced rats, thereby increasing the total fraction of IF metabolized via the activation pathway from 36% to 54% (P < 0.05), whereas the P450 inhibitors orphenadrine and troleandomycin had no significant affect on AUC values. These findings demonstrate specific roles for P450 2B and 3A enzymes in catalysing these pathways of IF metabolism in vivo, and demonstrate the potential for modulation of IF's alternative metabolic pathways in a therapeutically useful manner. These studies also highlight several clinically relevant drug interactions that may occur during concomitant administration of IF with drugs and other compounds that modulate hepatic P450 enzyme levels.

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“…Differential induction of microsomal CYP activities by aryl hydrocarbons and phenobarbital was discovered over 50 years ago [1][2][3][4], and facilitated characterization of the CYP supergene family [5,6]. This discovery also stimulated identification of the responsible ligand-activated transcription factors (LATFs): AhR [7,8], CAR and PXR [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans

Bock¹

2011

Biochemical Pharmacology

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. From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans. Biochemical Pharmacology, Elsevier, 2011, 82 (1) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64

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P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature

Cited by 2,553 publications

References 0 publications

The effect of smoking on postoperative nausea and vomiting

The effect of smoking on postoperative nausea and vomiting

Modulation of P450-dependent ifosfamide pharmacokinetics: a better understanding of drug activation in vivo

From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans

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