nicone-Δ1’,(5’)-iminium ion

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: nicone-Δ1’,(5’)-iminium ion
• 英文别名: 3-[(2R)-1-methyl-3,4-dihydro-2H-pyrrol-1-ium-2-yl]pyridine
• 化学式: C₁₀H₁₃N₂
• 分子量: 161.227
• InChiKey: GTQXYYYOJZZJHL-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.63
• 重原子数：
  12.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  15.9
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为产物：
  描述：

  烟碱 在 glucose-6-phosphate dehydrogenase 、 D-葡萄糖-6-磷酸 、 cytochrome P₄₅₀ 2A₁₃ 、 β-nicotinamide-adenine dinucleotide phosphate 、 magnesium chloride 作用下， 以 aq. phosphate buffer 为溶剂， 反应 0.33h， 生成 nicone-Δ1’,(5’)-iminium ion
  参考文献：
  名称：

  Functional characterization of 9 CYP2A13 allelic variants by assessment of nicotine C-oxidation and coumarin 7-hydroxylation

  摘要：

  Cytochrome P450 2A13 (CYP2A13) is responsible for the metabolism of chemical compounds such as nicotine, coumarin, and tobacco-specific nitrosamine. Several of these compounds have been recognized as procarcinogens activated by CYP2A13. We recently showed that CYP2A13*2 contributes to inter-individual variations observed in bladder cancer susceptibility because CYP2A13*2 might cause a decrease in enzymatic activity. Other CYP2A13 allelic variants may also affect cancer susceptibility. In this study, we performed an in vitro analysis of the wild-type enzyme (CYP2A13.1) and 8 CYP2A13 allelic variants, using nicotine and coumarin as representative CYP2A13 substrates. These CYP2A13 variant proteins were heterologously expressed in 293FT cells, and the kinetic parameters of nicotine C-oxidation and coumarin 7-hydroxylation were estimated. The quantities of CYP2A13 holoenzymes in microsomal fractions extracted from 293FT cells were determined by measuring reduced carbon monoxide-difference spectra. The kinetic parameters for CYP2A13.3, CYP2A13.4, and CYP2A13.10 could not be determined because of low metabolite concentrations. Five other CYP2A13 variants (CYP2A13.2, CYP2A13.5, CYP2A13.6, CYP2A13.8, and CYP2A13.9) showed markedly reduced enzymatic activity toward both substrates. These findings provide insights into the mechanism underlying inter-individual differences observed in genotoxicity and cancer susceptibility. (c) 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.dmpk.2017.11.004

文献信息

• Functional characterization of 9 CYP2A13 allelic variants by assessment of nicotine C-oxidation and coumarin 7-hydroxylation
  作者：Masaki Kumondai、Hiroki Hosono、Masamitsu Maekawa、Hiroaki Yamaguchi、Nariyasu Mano、Akifumi Oda、Noriyasu Hirasawa、Masahiro Hiratsuka

  DOI：10.1016/j.dmpk.2017.11.004

  日期：2018.2

  Cytochrome P450 2A13 (CYP2A13) is responsible for the metabolism of chemical compounds such as nicotine, coumarin, and tobacco-specific nitrosamine. Several of these compounds have been recognized as procarcinogens activated by CYP2A13. We recently showed that CYP2A13*2 contributes to inter-individual variations observed in bladder cancer susceptibility because CYP2A13*2 might cause a decrease in enzymatic activity. Other CYP2A13 allelic variants may also affect cancer susceptibility. In this study, we performed an in vitro analysis of the wild-type enzyme (CYP2A13.1) and 8 CYP2A13 allelic variants, using nicotine and coumarin as representative CYP2A13 substrates. These CYP2A13 variant proteins were heterologously expressed in 293FT cells, and the kinetic parameters of nicotine C-oxidation and coumarin 7-hydroxylation were estimated. The quantities of CYP2A13 holoenzymes in microsomal fractions extracted from 293FT cells were determined by measuring reduced carbon monoxide-difference spectra. The kinetic parameters for CYP2A13.3, CYP2A13.4, and CYP2A13.10 could not be determined because of low metabolite concentrations. Five other CYP2A13 variants (CYP2A13.2, CYP2A13.5, CYP2A13.6, CYP2A13.8, and CYP2A13.9) showed markedly reduced enzymatic activity toward both substrates. These findings provide insights into the mechanism underlying inter-individual differences observed in genotoxicity and cancer susceptibility. (c) 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.