From Wikipedia, the free encyclopedia
24S-Hydroxycholesterol
Names
IUPAC name
(24S )-Cholest-5-ene-3β,24-diol
Systematic IUPAC name
(1R ,3aS ,3bS ,7S ,9aR ,9bS ,11aR )-1-[(2R ,5S )-5-Hydroxy-6-methylheptan-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H -cyclopenta[a ]phenanthren-7-ol
Other names
cerebrosterol
Identifiers
3218472
ChEBI
ChEMBL
ChemSpider
KEGG
UNII
InChI=1S/C27H46O2/c1-17(2)25(29)11-6-18(3)22-9-10-23-21-8-7-19-16-20(28)12-14-26(19,4)24(21)13-15-27(22,23)5/h7,17-18,20-25,28-29H,6,8-16H2,1-5H3/t18-,20+,21+,22-,23+,24+,25+,26+,27-/m1/s1
Key: IOWMKBFJCNLRTC-XWXSNNQWSA-N
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
Properties
C 27 H 46 O 2
Molar mass
402.663 g·mol−1
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
24S -Hydroxycholesterol (24S-HC ), also known as cholest-5-ene-3,24-diol or cerebrosterol , is an
endogenous
oxysterol produced by
neurons in the
brain to maintain
cholesterol
homeostasis .
[1] It was discovered in 1953 by Alberto Ercoli, S. Di Frisco, and Pietro de Ruggieri, who first isolated the molecule in the horse brain
[2] and then demonstrated its presence in the
human brain .
[3]
Structure
24S-HC is produced by a
hydroxy group
substitution at
carbon number 24 in cholesterol, catalyzed by the
enzyme
cholesterol 24-hydroxylase (CYP46A1).
[4]
Production of 24S-hydroxycholesterol from cholesterol, as catalyzed by
CYP46A1 .
Function
24S-HC binds to
apolipoproteins such as
apoE ,
apoJ , and
apoA1 to form
HDL -like complexes
[5] which can cross the
blood–brain barrier more easily than free
cholesterol . Thus, 24S-HC production serves as one of several counterbalancing mechanisms for cholesterol synthesis in the brain.
[1]
[6] After entering general blood circulation and traveling to the
liver , 24S-HC can be
sulfated ,
glucuronidated , or converted into
bile acids , which can ultimately be
excreted .
[7]
24S-HC is an agonist of
liver X receptors , a class of
nuclear receptors that sense oxysterols. In the brain,
liver X receptor beta is the primary LXR type, which interacts with 24S-HC.
[5] 24S-HC levels sensed by LXRs can regulate the expression of
SREBP mRNA and protein, which in turn regulate
cholesterol synthesis and
fatty acid synthesis .
[8]
24S-HC may participate in several aspects of
brain development and function, such as
axon and
dendrite growth or
synaptogenesis ,
[4] as well as acting as a positive
allosteric modulator of
NMDA receptors .
[9] Regulation of 24S-HC metabolism in neurons may play a role in their health and function, as well as their response to injury or disease.
[10]
Blood plasma levels of 24S-HC may be altered after acute
brain injuries such as
stroke
[11] or in
neurodegenerative diseases such as
Alzheimer's disease ,
Huntington's disease , and
multiple sclerosis .
[12]
[13]
References
^
a
b Mahley RW (2016).
"Central Nervous System Lipoproteins: ApoE and Regulation of Cholesterol Metabolism" . Arterioscler Thromb Vasc Biol . 36 (7): 1305–15.
doi :
10.1161/ATVBAHA.116.307023 .
PMC
4942259 .
PMID
27174096 .
^ Ercoli A, Di Frisco S, De Ruggieri P (1953). "Isolation, constitution and biological significance of cerebrosterol, a companion of cholesterol in the horse brain". Boll Soc Ital Biol Sper . 29 (4): 494–7.
PMID
13105923 .
^ Di Frisco S, De Ruggieri P, Ercoli A (1953). "Isolation of cerebrosterol from human brain". Boll Soc Ital Biol Sper . 29 (7): 1351–2.
PMID
13140512 .
^
a
b Lund EG, Xie C, Kotti T, Turley SD, Dietschy JM, Russell DW (2003).
"Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover" . J Biol Chem . 278 (25): 22980–8.
doi :
10.1074/jbc.M303415200 .
PMID
12686551 .
^
a
b Wang Y, Kumar N, Crumbley C, Griffin PR, Burris TP (2010).
"A second class of nuclear receptors for oxysterols: Regulation of RORalpha and RORgamma activity by 24S-hydroxycholesterol (cerebrosterol)" . Biochim Biophys Acta . 1801 (8): 917–23.
doi :
10.1016/j.bbalip.2010.02.012 .
PMC
2886165 .
PMID
20211758 .
^ Björkhem I (2007). "Rediscovery of cerebrosterol". Lipids . 42 (1): 5–14.
doi :
10.1007/s11745-006-1003-2 .
PMID
17393206 .
S2CID
4005673 .
^ Lütjohann D (2006). "Cholesterol metabolism in the brain: importance of 24S-hydroxylation". Acta Neurol Scand Suppl . 185 : 33–42.
doi :
10.1111/j.1600-0404.2006.00683.x .
PMID
16866909 .
S2CID
44809894 .
^ Cartagena CM, Burns MP, Rebeck GW (2010).
"24S-hydroxycholesterol effects on lipid metabolism genes are modeled in traumatic brain injury" . Brain Res . 1319 : 1–12.
doi :
10.1016/j.brainres.2009.12.080 .
PMC
2826556 .
PMID
20053345 .
^ Paul SM, Doherty JJ, Robichaud AJ, Belfort GM, Chow BY, Hammond RS, Crawford DC, Linsenbardt AJ, Shu HJ, Izumi Y, Mennerick SJ, Zorumski CF (October 2013).
"The major brain cholesterol metabolite 24(S)-hydroxycholesterol is a potent allosteric modulator of N-methyl-D-aspartate receptors" .
The Journal of Neuroscience . 33 (44): 17290–300.
doi :
10.1523/JNEUROSCI.2619-13.2013 .
PMC
3812502 .
PMID
24174662 .
^ Sun MY, Linsenbardt AJ, Emnett CM, Eisenman LN, Izumi Y, Zorumski CF, Mennerick S (2016).
"24(S)-Hydroxycholesterol as a Modulator of Neuronal Signaling and Survival" . Neuroscientist . 22 (2): 132–44.
doi :
10.1177/1073858414568122 .
PMC
4821654 .
PMID
25628343 .
^ Sun MY, Taylor A, Zorumski CF, Mennerick S (2017).
"24S-hydroxycholesterol and 25-hydroxycholesterol differentially impact hippocampal neuronal survival following oxygen-glucose deprivation" . PLOS ONE . 12 (3): e0174416.
Bibcode :
2017PLoSO..1274416S .
doi :
10.1371/journal.pone.0174416 .
PMC
5367825 .
PMID
28346482 .
^ Leoni V, Caccia C (2013). "24S-hydroxycholesterol in plasma: a marker of cholesterol turnover in neurodegenerative diseases". Biochimie . 95 (3): 595–612.
doi :
10.1016/j.biochi.2012.09.025 .
PMID
23041502 .
^ Bandaru VV, Haughey NJ (2014).
"Quantitative detection of free 24S-hydroxycholesterol, and 27-hydroxycholesterol from human serum" . BMC Neurosci . 15 : 137.
doi :
10.1186/s12868-014-0137-z .
PMC
4304132 .
PMID
25539717 .