4beta,24S-dihydroxycholesterol

• 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: 4beta,24S-dihydroxycholesterol
• 英文别名: (3S,4R,8S,9S,10R,13R,14S,17R)-17-[(2R,5S)-5-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,4-diol
• 化学式: C₂₇H₄₆O₃
• 分子量: 418.7
• InChiKey: IWXJGKGAPXGSCN-GCUSXLOISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  30
• 可旋转键数：
  5
• 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：

  4-Beta-羟基胆固醇 、 氧气 、 1-Deoxy-1-(7,8-dimethyl-2,4-dioxidobenzo[g]pteridin-10(5H)-yl)-5-O-phosphonopentitol 生成 4beta,24S-dihydroxycholesterol 、 氢(+1)阳离子 、 水 、 FMN
  参考文献：
  名称：

  Metabolism of 4β-Hydroxycholesterol in Humans

  摘要：

  One of the major oxysterols in the human circulation is 4beta-hydroxycholesterol formed from cholesterol by the drug-metabolizing enzyme cytochrome P450 3A4. Deuterium-labeled 4beta-hydroxycholesterol was injected into two healthy volunteers, and the apparent half-life was found to be 64 and 60 h, respectively. We have determined earlier the half-lives for 7alpha-, 27-, and 24-hydroxycholesterol to be similar to0.5, 0.75, and 14 h, respectively. Patients treated with certain antiepileptic drugs have up to 20-fold increased plasma concentrations of 4beta-hydroxycholesterol. The apparent half-life of deuteriumlabeled 4beta-hydroxycholesterol in such a patient was found to be 52 h, suggesting that the high plasma concentration was because of increased synthesis rather than impaired clearance. 4beta-Hydroxycholesterol was converted into acidic products at a much slower rate than 7alpha-hydroxycholesterol in primary human hepatocytes, and 4beta-hydroxycholesterol was 7alpha-hydroxylated at a slower rate than cholesterol by recombinant human CYP7A1. CYP7B1 and CYP39A1 had no activity toward 4beta-hydroxycholesterol. These results suggest that the high plasma concentration of 4beta-hydroxycholesterol is because of its exceptionally slow elimination, probably in part because of the low rate of 7alpha-hydroxylation of the steroid. The findings are discussed in relation to a potential role of 4beta-hydroxycholesterol as a ligand for the nuclear receptor LXR.

  DOI：

  10.1074/jbc.m201712200

文献信息

• Metabolism of 4β-Hydroxycholesterol in Humans
  作者：Karl Bodin、Ulla Andersson、Eva Rystedt、Ewa Ellis、Maria Norlin、Irina Pikuleva、Gösta Eggertsen、Ingemar Björkhem、Ulf Diczfalusy

  DOI：10.1074/jbc.m201712200

  日期：2002.8

  One of the major oxysterols in the human circulation is 4beta-hydroxycholesterol formed from cholesterol by the drug-metabolizing enzyme cytochrome P450 3A4. Deuterium-labeled 4beta-hydroxycholesterol was injected into two healthy volunteers, and the apparent half-life was found to be 64 and 60 h, respectively. We have determined earlier the half-lives for 7alpha-, 27-, and 24-hydroxycholesterol to be similar to0.5, 0.75, and 14 h, respectively. Patients treated with certain antiepileptic drugs have up to 20-fold increased plasma concentrations of 4beta-hydroxycholesterol. The apparent half-life of deuteriumlabeled 4beta-hydroxycholesterol in such a patient was found to be 52 h, suggesting that the high plasma concentration was because of increased synthesis rather than impaired clearance. 4beta-Hydroxycholesterol was converted into acidic products at a much slower rate than 7alpha-hydroxycholesterol in primary human hepatocytes, and 4beta-hydroxycholesterol was 7alpha-hydroxylated at a slower rate than cholesterol by recombinant human CYP7A1. CYP7B1 and CYP39A1 had no activity toward 4beta-hydroxycholesterol. These results suggest that the high plasma concentration of 4beta-hydroxycholesterol is because of its exceptionally slow elimination, probably in part because of the low rate of 7alpha-hydroxylation of the steroid. The findings are discussed in relation to a potential role of 4beta-hydroxycholesterol as a ligand for the nuclear receptor LXR.