Human cytochrome P450 2A13 efficiently metabolizes chemicals in air pollutants: naphthalene, styrene, and toluene
Fukami, T; Katoh, M; Yamazaki, H; Yokoi, T; Nakajima, M
HERO ID
1468245
Reference Type
Journal Article
Year
2008
Language
English
PMID
| HERO ID | 1468245 |
|---|---|
| In Press | No |
| Year | 2008 |
| Title | Human cytochrome P450 2A13 efficiently metabolizes chemicals in air pollutants: naphthalene, styrene, and toluene |
| Authors | Fukami, T; Katoh, M; Yamazaki, H; Yokoi, T; Nakajima, M |
| Journal | Chemical Research in Toxicology |
| Volume | 21 |
| Issue | 3 |
| Page Numbers | 720-725 |
| Abstract | Human P450 2A13 is the most efficient enzyme for catalyzing the metabolism of nicotine and metabolic activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). It is conceivable that P450 2A13 also metabolizes chemicals in air pollutants because this enzyme is highly expressed in the respiratory tract. In this study, we investigated the possibility that P450 2A13 can metabolize naphthalene, styrene, and toluene, which are included in air pollutants as well as tobacco smoke, although they were known to be metabolized by P450 1A2 or 2E1. We found that P450 2A13 catalyzed 1- and 2-naphthol formations from naphthalene with higher intrinsic clearances ( kcat/ Km) (3.1- and 2.2-fold, respectively) than P450 1A2 and also more efficiently catalyzed the styrene 7,8-oxide formation from styrene and the benzylalcohol formation from toluene than P450 2E1. The overlapping substrate specificity of P450 2A13 with P450 2E1 was supported by the finding that P450 2A13 catalyzed chlorzoxazone 6-hydroxylation (8-fold higher value of kcat/ Km) and p-nitrophenol 2-hydroxylation (19-fold higher value of kcat/ Km), which are marker activities of P450 2E1. Thus, we found that P450 2A13 metabolizes diverse environmental chemicals and has overlapping substrate specificities of P450 1A2 and 2E1, suggesting that P450 2A13 plays important roles in the local metabolism of environmental chemicals in the respiratory tract related to toxicity or carcinogenicity. |
| Doi | 10.1021/tx700325f |
| Pmid | 18266326 |
| Wosid | WOS:000254085300021 |
| Url | https://www.proquest.com/scholarly-journals/human-cytochrome-p450-2a13-efficiently/docview/70400612/se-2?accountid=171501 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000254085300021Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-41849093006&doi=10.1021%2ftx700325f&partnerID=40&md5=f041b76a977871968faceac7298c409f |
| Is Public | Yes |
| Language Text | English |
| Keyword | Air Pollutants; Membrane Proteins; Naphthalenes; Naphthols; Styrenes; 1-naphthol; 2A71EAQ389; Toluene; 3FPU23BG52; Cyp3a13 protein, mouse; EC 1.14.14.1; Cytochrome P-450 CYP3A; Index Medicus; Naphthols -- metabolism; Hydroxylation; Catalysis; Kinetics; Escherichia coli -- metabolism; Membrane Proteins -- metabolism; Cytochrome P-450 CYP3A -- metabolism; Toluene -- metabolism; Air Pollutants -- metabolism; Styrenes -- metabolism; Naphthalenes -- metabolism |