| Identification and characterization of functional rat arylamine N-acetyltransferase 3: comparisons with rat arylamine N-acetyltransferases 1 and 2. | |
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MedLine Citation:
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PMID: 16829624 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Arylamine N-acetyltransferases (NATs; EC 2.3.1.5) catalyze both the N-acetylation and O-acetylation of arylamines and N-hydroxyarylamines. Humans possess two functional N-acetyltransferase genes, NAT1 and NAT2, as well as a nonfunctional pseudogene, NATP. Previous studies have identified Nat1 and Nat2 genes in the rat. In this study, we identified and characterized a third rat N-acetyltransferase gene (Nat3) consisting of a single open reading frame of 870 base pairs encoding a 290-amino acid protein, analogous to the previously identified human and rat N-acetyltransferase genes. Rat Nat3 nucleotide sequence was 77.2 and 75.9% identical to human NAT1 and NAT2, respectively. Rat Nat3 amino acid sequence was 68.6 and 67.2% identical to human NAT1 and NAT2, respectively. Rat Nat1, Nat2, and Nat3 were each cloned and recombinantly expressed in Escherichia coli. Recombinant rat Nat3 exhibited thermostability intermediate between recombinant rat Nat1 and Nat2. Recombinant rat Nat3 was functional and catalyzed the N-acetylation of several arylamine substrates, including 3-ethylaniline, 3,5-dimethylaniline, 5-aminosalicylic acid, 4-aminobiphenyl, 4,4'-methylenedianiline, 4,4'-methylenebis(2-chloroaniline), and 2-aminofluorene, and the O-acetylation of N-hydroxy-4-aminobiphenyl. The relative affinities of arylamine carcinogens such as 4-aminobiphenyl, N-hydroxy-4-aminobiphenyl, and 2-aminofluorene for N- and O-acetylation via recombinant rat Nat3 were comparable with recombinant rat Nat1 and higher than for recombinant rat Nat2. This study is the first to report a third arylamine N-acetyltransferase isozyme with significant functional capacity. |
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Authors:
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Jason M Walraven; Mark A Doll; David W Hein |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural Date: 2006-07-07 |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 319 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-09-26 Completed Date: 2006-11-02 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
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Languages: eng Pagination: 369-75 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Arylamine N-Acetyltransferase / genetics, metabolism* Cloning, Molecular Enzyme Stability Humans Isoenzymes / genetics, metabolism* Kinetics Mice Molecular Sequence Data Rats Rats, Inbred F344 Rats, Inbred WKY Rats, Sprague-Dawley |
| Grant Support | |
ID/Acronym/Agency:
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CA34627/CA/NCI NIH HHS; ES011564/ES/NIEHS NIH HHS; R01 CA034627-21/CA/NCI NIH HHS; T32 ES011564-03/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Isoenzymes; EC 2.3.1.5/Arylamine N-Acetyltransferase; EC 2.3.1.5/N-acetyltransferase 1 |
| Comments/Corrections | |
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