Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
A novel single nucleotide polymorphism altering stability and activity of CYP2A6
Autore:
Ariyoshi, N; Sawamura, Y; Kamataki, T;
Indirizzi:
Hokkaido Univ, Grad Sch Pharmaceut Sci, Lab Drug Metab, Kita Ku, Sapporo, Hokkaido 0600812, Japan Hokkaido Univ Sapporo Hokkaido Japan 0600812 oro, Hokkaido 0600812, Japan Maruyama Clin, Sapporo, Hokkaido 0640820, Japan Maruyama Clin Sapporo Hokkaido Japan 0640820 oro, Hokkaido 0640820, Japan
Titolo Testata:
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
fascicolo: 3, volume: 281, anno: 2001,
pagine: 810 - 814
SICI:
0006-291X(20010302)281:3<810:ANSNPA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN LIVER-MICROSOMES; CYTOCHROME-P450 2A6; NICOTINE METABOLISM; GENE; DELETION; IDENTIFICATION; HYDROCHLORIDE; SUBSTRATE; SMOKING;
Keywords:
cytochrome P450; genetic polymorphism; nicotine; genetic linkage; genotyping; allele specific PCR; poor metabolizers;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
17
Recensione:
Indirizzi per estratti:
Indirizzo: Kamataki, T Hokkaido Univ, Grad Sch Pharmaceut Sci, Lab Drug Metab, Kita Ku, N12W6, Sapporo, Hokkaido 0600812, Japan Hokkaido Univ N12W6 Sapporo Hokkaido Japan 0600812 0812, Japan
Citazione:
N. Ariyoshi et al., "A novel single nucleotide polymorphism altering stability and activity of CYP2A6", BIOC BIOP R, 281(3), 2001, pp. 810-814

Abstract

CYP2A6 is known as a major cytochrome P450 (CYP) responsible for the oxidation of nicotine and coumarin in humans. In this study, we explored geneticpolymorphisms, which reduce CYP2A6 activity in Japanese. Two novel mutations in exon 9 of the CYP2A6 gene were found. A single nucleotide polymorphism of T1412C and G1454T resulted in Ile471Thr and Arg485Leu substitution, respectively. The frequency of the former variant allele was considerably high (15.7%), while the latter variant appeared to be a rare polymorphism. Heterologous expression of CYP2A6 using a cDNA possessing C instead of T-base at codon 471 in Escherichia coli caused remarkable reduction of the stability of holoenzyme at 37 degreesC. Furthermore, this variant enzyme almost lacked nicotine C-oxidase activity, although coumarin 7-hydroxylase activity was still observed. These data suggest that individuals homozygous for the T1412C variant allele or heterozygous for this and a defect allele such as the CYP2A6*4 may be poor metabolizer of nicotine, but not coumarin. (C) 2001 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 09:54:25