脑甾醇

脑甾醇
	IUPAC名; cholest-5-ene-3,24-diol
别名	cerebrosterol
识别
CAS号	474-73-7
PubChem	121948
ChemSpider	108790
SMILES	C[C@H](CC[C@@H](C(C)C)O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H](C4)O)C)C;
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（英語：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]：

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.

[pmid27174096-1] 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.

[pmid13105923-2] 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.

[pmid13140512-3] 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.

[pmid12686551-4] 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）.

[pmid20211758-5] 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）.

[pmid17393206-6] Björkhem I. Rediscovery of cerebrosterol.. Lipids. 2007, 42 (1): 5–14. PMID 17393206. doi:10.1007/s11745-006-1003-2.

[pmid16866909-7] 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.

[pmid20053345-8] 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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