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Wikipedia

24S-Hydroxycholesterol

April 14, 2024

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]

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
  • 474-73-7
3D model (JSmol)
  • Interactive image
3218472
ChEBI
  • CHEBI:34310
ChEMBL
  • ChEMBL171804
ChemSpider
  • 108790
KEGG
  • C13550
  • 121948
UNII
  • 47IMW63S3F
  • 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
C27H46O2
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).

Structure edit

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 edit

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 edit

  1. ^ 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.
  2. ^ 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.
  3. ^ 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.
  4. ^ 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.
  5. ^ 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.
  6. ^ Björkhem I (2007). "Rediscovery of cerebrosterol". Lipids. 42 (1): 5–14. doi:10.1007/s11745-006-1003-2. PMID 17393206. S2CID 4005673.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.

April 14, 2024
hydroxycholesterol, also, known, cholest, diol, cerebrosterol, endogenous, oxysterol, produced, neurons, brain, maintain, cholesterol, homeostasis, discovered, 1953, alberto, ercoli, frisco, pietro, ruggieri, first, isolated, molecule, horse, brain, then, demo. 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 24S Hydroxycholesterol NamesIUPAC name 24S Cholest 5 ene 3b 24 diolSystematic 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 olOther names cerebrosterolIdentifiersCAS Number 474 73 73D model JSmol Interactive imageBeilstein Reference 3218472ChEBI CHEBI 34310ChEMBL ChEMBL171804ChemSpider 108790KEGG C13550PubChem CID 121948UNII 47IMW63S3FInChI 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 s1Key IOWMKBFJCNLRTC XWXSNNQWSA NSMILES 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 CPropertiesChemical formula C 27H 46O 2Molar mass 402 663 g mol 1Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Infobox referencesStructure edit24S HC is produced by a hydroxy group substitution at carbon number 24 in cholesterol catalyzed by the enzyme cholesterol 24 hydroxylase CYP46A1 4 nbsp Production of 24S hydroxycholesterol from cholesterol as catalyzed by CYP46A1 Function edit24S 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 edit 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 Bjorkhem I 2007 Rediscovery of cerebrosterol Lipids 42 1 5 14 doi 10 1007 s11745 006 1003 2 PMID 17393206 S2CID 4005673 Lutjohann 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 Retrieved from https en wikipedia org w index php title 24S Hydroxycholesterol amp oldid 1186232966, wikipedia, wiki, book, books, library,

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