腦甾醇

腦甾醇
	IUPAC名; cholest-5-ene-3,24-diol
別名	cerebrosterol
識別
CAS號	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
性質
化學式	C27H46O2
摩爾質量	402.653 g/mol g·mol⁻¹
	若非註明，所有數據均出自標準狀態（25 ℃，100 kPa）下。

腦甾醇（英語：cerebrosterol）或稱為24S-羥基膽固醇（24S-hydroxycholesterol，縮寫24S-HC，即膽甾-5-烯-3β,24S-二醇，cholest-5-ene-3,24-diol）是一種內源性的氧化膽固醇，由大腦中的神經元產生，來維持膽固醇穩態^[1]。腦甾醇最早於1953年由Alberto Ercoli, S. Di Frisco, 和Pietro de Ruggieri三位科學家在馬的大腦中發現^[2]，之後發現人腦中也存在^[3]。

結構[編輯]

24S-HC由膽固醇在24號碳原子上S位置的氫發生羥基基團取代反應生成，此反應由酶膽固醇24-羥化酶（CYP46A1）催化^[4]：

功能[編輯]

24S-HC可與載脂蛋白結合，如apoE、apoJ和apoA1等，來形成高密度脂蛋白樣複合物^[5]，因此比游離的膽固醇更容易通過血腦屏障。因此，24S-HC的生產是大腦合成膽固醇的幾種平衡機制之一^[1]^[6]。在進入血液循環後，24S-HC轉運至肝臟，24S-HC在此可發生硫酸化、葡糖醛酸化或轉化為膽酸，最終排出體外^[7]。

24S-HC也是肝X受體（LXR）的激動劑，肝X受體是一類感應氧化膽固醇的核受體。在大腦中，與24S-HC作用的LXR主要是肝X受體β（LXRβ）^[5]。24S-HC激活LXR，促進固醇調節元件結合蛋白（SREBP）的mRNA轉錄與蛋白的表達，來調控膽固醇合成和脂肪酸合成^[8]。

參考文獻[編輯]

^ ^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. （原始內容存檔於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. （原始內容存檔於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. （原始內容存檔於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. （原始內容存檔於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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