(24S,25S)-cholest-5-en-3beta,24,26-triol

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (24S,25S)-cholest-5-en-3beta,24,26-triol
• 英文别名: (2S,3S,6R)-6-[(3S,8S,9S,10R,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-methylheptane-1,3-diol
• 化学式: C₂₇H₄₆O₃
• 分子量: 418.7
• InChiKey: XMULUVSUDUCTFU-QDKHZERXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (3Β,24S)-胆甾-5-烯-3,24-二醇 、 氧气 、 1-Deoxy-1-(7,8-dimethyl-2,4-dioxidobenzo[g]pteridin-10(5H)-yl)-5-O-phosphonopentitol 生成 (24S,25S)-cholest-5-en-3beta,24,26-triol 、 氢(+1)阳离子 、 水 、 FMN
  参考文献：
  名称：

  Broad Substrate Specificity of Human Cytochrome P450 46A1 Which Initiates Cholesterol Degradation in the Brain

  摘要：

  The known activity of cytochrome P450 46A1 (P450 46A1) is 24(S)-hydroxylation of cholesterol. This reaction produces biologically active oxysterol, 2 4(S) -hydrox ychol e sterol, and is also the first step in enzymatic degradation of cholesterol in the brain. We report here that P450 46A1 can further metabolize 24(S)-hydroxycholesterol, giving 24,25- and 24,27-dihydroxycholesterols in both the cell cultures transfected with P450 46A1 cDNA and the in vitro reconstituted system with recombinant enzyme. In addition, P450 46A1 was able to carry out side chain hydroxylations of two endogenous C27-steroids with and without a double bond between C5-C6 (7alpha-hydroxycholesterol and cholestanol, respectively) and introduce a hydroxyl group on the steroid nucleus of the C21-steroid hormones with the C4-C5 double bond (progesterone and testosterone). Also, P450 46A1 was found to metabolize xenobiotics carrying out dextromethorphan O- and N-demethylations, diclofenac 4'-hydroxylation, and phenacetin O-deethylation. Thus, substrate specificities of P450 46A1 are not limited to cholesterol and include a number of structurally diverse compounds. Activities of P450 46A1 suggest that, in addition to the involvement in cholesterol homeostasis in the brain, this enzyme may participate in metabolism of neurosteroids and drugs that can cross the blood-brain barrier and are targeted to the central nervous system.

  DOI：

  10.1021/bi035512f

文献信息

• Broad Substrate Specificity of Human Cytochrome P450 46A1 Which Initiates Cholesterol Degradation in the Brain
  作者：Natalia Mast、Ryan Norcross、Ulla Andersson、Magang Shou、Kazuo Nakayama、Ingemar Bjorkhem、Irina A. Pikuleva

  DOI：10.1021/bi035512f

  日期：2003.12.1

  The known activity of cytochrome P450 46A1 (P450 46A1) is 24(S)-hydroxylation of cholesterol. This reaction produces biologically active oxysterol, 2 4(S) -hydrox ychol e sterol, and is also the first step in enzymatic degradation of cholesterol in the brain. We report here that P450 46A1 can further metabolize 24(S)-hydroxycholesterol, giving 24,25- and 24,27-dihydroxycholesterols in both the cell cultures transfected with P450 46A1 cDNA and the in vitro reconstituted system with recombinant enzyme. In addition, P450 46A1 was able to carry out side chain hydroxylations of two endogenous C27-steroids with and without a double bond between C5-C6 (7alpha-hydroxycholesterol and cholestanol, respectively) and introduce a hydroxyl group on the steroid nucleus of the C21-steroid hormones with the C4-C5 double bond (progesterone and testosterone). Also, P450 46A1 was found to metabolize xenobiotics carrying out dextromethorphan O- and N-demethylations, diclofenac 4'-hydroxylation, and phenacetin O-deethylation. Thus, substrate specificities of P450 46A1 are not limited to cholesterol and include a number of structurally diverse compounds. Activities of P450 46A1 suggest that, in addition to the involvement in cholesterol homeostasis in the brain, this enzyme may participate in metabolism of neurosteroids and drugs that can cross the blood-brain barrier and are targeted to the central nervous system.