13-Hydroxy-gamma-tocopherol

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 13-Hydroxy-gamma-tocopherol
• 英文别名: (2R)-2-[(4R,8S)-13-hydroxy-4,8,12-trimethyltridecyl]-2,7,8-trimethyl-3,4-dihydrochromen-6-ol
• 化学式: C₂₈H₄₈O₃
• 分子量: 432.7
• InChiKey: QNBPVJMQPAQXML-WQSDRKHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  31
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  D-gamma-生育酚 、 氢(+1)阳离子 、 NADPH(4-) 、 氧气 生成 13-Hydroxy-gamma-tocopherol 、 水 、 NADP⁺
  参考文献：
  名称：

  Cytochrome P450 ω-Hydroxylase Pathway of Tocopherol Catabolism

  摘要：

  Postabsorptive elimination of the various forms of vitamin E appears to play a key role in regulation of tissue tocopherol concentrations, but mechanisms of tocopherol metabolism have not been elucidated. Here we describe a pathway involving cytochrome P450-mediated omega-hydroxylation of the tocopherol phytyl side chain followed by stepwise removal of two- or three-carbon moieties, ultimately yielding the X-carboxychromanol metabolite that is excreted in urine. All key intermediates of gamma-tocopherol metabolism via this pathway were identified in hepatocyte cultures using gas chromatographymass spectrometry. NADPH-dependent synthesis of the initial gamma- and alpha-tocopherol 13'-hydroxy and -carboxy metabolites was demonstrated in rat and human liver microsomes. Functional analysis of several recombinant human liver P450 enzymes revealed that tocopherol-cohydroxylase activity was associated only with CYP4F2, which also catalyzes omega-hydroxylation of leukotriene B-4 and arachidonic acid. Tocopherol-omega-hydroxylase exhibited similar binding affinities but markedly higher catalytic activities for gamma-tocopherol than alpha-tocopherol, suggesting a role for this pathway in the preferential physiological retention of alpha-tocopherol and elimination of gamma-tocopherol. Sesamin potently inhibited tocopherol-omega-hydroxylase activity exhibited by CYP4F2 and rat or human liver microsomes. Since dietary sesamin also results in elevated tocopherol levels in vivo, this pathway appears to represent a functionally significant means of regulating vitamin E status.

  DOI：

  10.1074/jbc.m201466200

文献信息

• Cytochrome P450 ω-Hydroxylase Pathway of Tocopherol Catabolism
  作者：Timothy J. Sontag、Robert S. Parker

  DOI：10.1074/jbc.m201466200

  日期：2002.7

  Postabsorptive elimination of the various forms of vitamin E appears to play a key role in regulation of tissue tocopherol concentrations, but mechanisms of tocopherol metabolism have not been elucidated. Here we describe a pathway involving cytochrome P450-mediated omega-hydroxylation of the tocopherol phytyl side chain followed by stepwise removal of two- or three-carbon moieties, ultimately yielding the X-carboxychromanol metabolite that is excreted in urine. All key intermediates of gamma-tocopherol metabolism via this pathway were identified in hepatocyte cultures using gas chromatographymass spectrometry. NADPH-dependent synthesis of the initial gamma- and alpha-tocopherol 13'-hydroxy and -carboxy metabolites was demonstrated in rat and human liver microsomes. Functional analysis of several recombinant human liver P450 enzymes revealed that tocopherol-cohydroxylase activity was associated only with CYP4F2, which also catalyzes omega-hydroxylation of leukotriene B-4 and arachidonic acid. Tocopherol-omega-hydroxylase exhibited similar binding affinities but markedly higher catalytic activities for gamma-tocopherol than alpha-tocopherol, suggesting a role for this pathway in the preferential physiological retention of alpha-tocopherol and elimination of gamma-tocopherol. Sesamin potently inhibited tocopherol-omega-hydroxylase activity exhibited by CYP4F2 and rat or human liver microsomes. Since dietary sesamin also results in elevated tocopherol levels in vivo, this pathway appears to represent a functionally significant means of regulating vitamin E status.