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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:02:46 UTC
HMDB IDHMDB00501
Secondary Accession NumbersNone
Metabolite Identification
Common Name7-Ketocholesterol
Description7-Ketocholesterol is a major oxidation product of cholesterol (oxysterol) found in human atherosclerotic plaque and is more atherogenic than cholesterol in some animal studies. Oxysterols (oxygenated forms of cholesterol) are present at low levels in the circulation and accumulate is plasma and tissues in some pathologies. In atherosclerotic lesions, 7-oxygenated oxysterols, predominantly 7-ketocholesterol, accumulate and have been implicated in the pathology of the disease. There is some in vivo and in vitro evidence that sterol 27-hydroxylase acts on 7-ketocholesterol to initiate its degradation to more polar, water-soluble products. Recent studies indicate an alternative mechanism, in which 7-ketocholesterol is reduced to 7 beta-hydroxycholesterol by 11 beta-hydroxysteroid dehydrogenase type 1. 7-Ketocholesterol can inhibit cholesterol 7 alpha-hydroxylase, the rate-limiting step in bile acid biosynthesis, as well as strongly inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. It has even been suggested that 7-ketocholesterol is formed enzymically as an endogenous regulator of cholesterol biosynthesis. However, when tested as a pharmacological cholesterol-lowering agent, inhibition of HMG-CoA reductase was rapidly overcome and the 7-ketocholesterol metabolised. In vitro, 7-ketocholesterol has wide-ranging and potent effects, most of which have the potential to contribute to atherosclerosis. For example, 7-ketocholesterol can be cytotoxic and can induce apoptosis in vascular cells. These effects, either individually or more likely, in combination, all implicate 7-ketocholesterol in the initiation and development of atherosclerosis, but further work is needed to establish whether or not its role is a direct causal one. 7-Ketocholesterol is the second most abundant oxysterol found in human atherosclerotic plaque, after the enzymically formed 27-hydroxycholesterol (cholest-5-ene-3beta,27-diol). 7-Ketocholesterol differs from cholesterol by a ketone functional group present at the 7-position. It is produced from cholesterol via the epimeric cholesterol 7-hydroperoxides (cholest-5-ene-3beta-ol-7-hydroperoxide) which decompose to the epimeric 7-hydroxycholesterols (cholest-5-ene-3beta,7-diol) and 7-ketocholesterol. 7-Ketocholesterol is a major dietary oxysterol. It has also been widely suggested that 7-ketocholesterol present in atherosclerotic tissue may be derived from the diet. Certainly, 7-ketocholesterol is a major oxysterol found in cholesterol-rich processed foodstuffs. Dietary 7-ketocholesterol is rapidly metabolised by the liver to 7beta-hydroxycholesterol (cholest-5-ene-3beta,7beta-diol), unusual bile acids and perhaps even cholesterol itself. Its conversion to 7beta-hydroxycholesterol is well documented. (PMID: 15798369 , 10224662 ).
Structure
Thumb
Synonyms
ValueSource
3b-Hydroxycholest-5-en-7-oneHMDB
7-OxocholesterolHMDB
Cholest-5-en-3b-ol-7-oneHMDB
Delta5-Cholesten-3b-ol-7-oneHMDB
Chemical FormulaC27H44O2
Average Molecular Weight400.6371
Monoisotopic Molecular Weight400.334130652
IUPAC Name(1S,2R,10S,11S,15R)-5-hydroxy-2,15-dimethyl-14-[(2R)-6-methylheptan-2-yl]tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-7-en-9-one
Traditional Name(1S,2R,10S,11S,15R)-5-hydroxy-2,15-dimethyl-14-[(2R)-6-methylheptan-2-yl]tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-7-en-9-one
CAS Registry Number566-28-9
SMILES
[H][C@@]12CCC([C@H](C)CCCC(C)C)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])C(=O)C=C2CC(O)CC[C@]12C
InChI Identifier
InChI=1S/C27H44O2/c1-17(2)7-6-8-18(3)21-9-10-22-25-23(12-14-27(21,22)5)26(4)13-11-20(28)15-19(26)16-24(25)29/h16-18,20-23,25,28H,6-15H2,1-5H3/t18-,20?,21?,22+,23+,25+,26+,27-/m1/s1
InChI KeyInChIKey=YIKKMWSQVKJCOP-QJFKPLHKSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as cholesterols and derivatives. These are compounds containing a 3-hydroxylated cholestane core.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassCholestane steroids
Direct ParentCholesterols and derivatives
Alternative Parents
Substituents
  • Cholesterol-skeleton
  • Cholesterol
  • 7-oxosteroid
  • Oxosteroid
  • Hydroxysteroid
  • 3-hydroxysteroid
  • 3-hydroxy-delta-5-steroid
  • Delta-5-steroid
  • Cyclic alcohol
  • Secondary alcohol
  • Ketone
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External DescriptorsNot Available
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Hormones, Membrane component
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point168 - 170 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.000208 mg/mLALOGPS
logP5.8ALOGPS
logP6.55ChemAxon
logS-6.3ALOGPS
pKa (Strongest Acidic)17.39ChemAxon
pKa (Strongest Basic)-1.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity121.26 m3·mol-1ChemAxon
Polarizability50.88 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, N/A (Annotated)splash10-0a4i-0009000000-82ed6dc62b49ac0340e6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, N/A (Annotated)splash10-0a5a-5910100000-41a560da8a3cd10710d8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, N/A (Annotated)splash10-05o1-9400000000-eef0253b6691ce201b6fView in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue Location
  • Myelin
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.033 +/- 0.018 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.122 +/- 0.083 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.014 +/- 0.008 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0021(0.00074-0.005) uMAdult (>18 years old)Not SpecifiedNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
Cerebrospinal Fluid (CSF)Detected and Quantified0.003(0.001-0.01) uMAdult (>18 years old)Not SpecifiedMultiple Sclerosis details
Associated Disorders and Diseases
Disease References
Multiple sclerosis
  1. Leoni V, Lutjohann D, Masterman T: Levels of 7-oxocholesterol in cerebrospinal fluid are more than one thousand times lower than reported in multiple sclerosis. J Lipid Res. 2005 Feb;46(2):191-5. Epub 2004 Dec 1. [15576852 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022079
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB00501
Metagene LinkHMDB00501
METLIN ID5487
PubChem Compound53477696
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceChicoye, Etzer; Powrie, William D.; Fennema, Owen R. Synthesis, purification, and characterization of 7-ketocholesterol and epimeric 7-hydroxycholesterols. Lipids (1968), 3(6), 551-6.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Pedruzzi E, Guichard C, Ollivier V, Driss F, Fay M, Prunet C, Marie JC, Pouzet C, Samadi M, Elbim C, O'dowd Y, Bens M, Vandewalle A, Gougerot-Pocidalo MA, Lizard G, Ogier-Denis E: NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells. Mol Cell Biol. 2004 Dec;24(24):10703-17. [15572675 ]
  2. Schweizer RA, Zurcher M, Balazs Z, Dick B, Odermatt A: Rapid hepatic metabolism of 7-ketocholesterol by 11beta-hydroxysteroid dehydrogenase type 1: species-specific differences between the rat, human, and hamster enzyme. J Biol Chem. 2004 Apr 30;279(18):18415-24. Epub 2004 Feb 18. [14973125 ]
  3. Miguet-Alfonsi C, Prunet C, Monier S, Bessede G, Lemaire-Ewing S, Berthier A, Menetrier F, Neel D, Gambert P, Lizard G: Analysis of oxidative processes and of myelin figures formation before and after the loss of mitochondrial transmembrane potential during 7beta-hydroxycholesterol and 7-ketocholesterol-induced apoptosis: comparison with various pro-apoptotic chemicals. Biochem Pharmacol. 2002 Aug 1;64(3):527-41. [12147305 ]
  4. Dulak J, Jozkowicz A, Dichtl W, Alber H, Schwarzacher SP, Pachinger O, Weidinger F: Vascular endothelial growth factor synthesis in vascular smooth muscle cells is enhanced by 7-ketocholesterol and lysophosphatidylcholine independently of their effect on nitric oxide generation. Atherosclerosis. 2001 Dec;159(2):325-32. [11730812 ]
  5. Miguet C, Monier S, Bettaieb A, Athias A, Bessede G, Laubriet A, Lemaire S, Neel D, Gambert P, Lizard G: Ceramide generation occurring during 7beta-hydroxycholesterol- and 7-ketocholesterol-induced apoptosis is caspase independent and is not required to trigger cell death. Cell Death Differ. 2001 Jan;8(1):83-99. [11313706 ]
  6. Lyons MA, Brown AJ: Metabolism of an oxysterol, 7-ketocholesterol, by sterol 27-hydroxylase in HepG2 cells. Lipids. 2001 Jul;36(7):701-11. [11521968 ]
  7. Berthier A, Lemaire-Ewing S, Prunet C, Montange T, Vejux A, Pais de Barros JP, Monier S, Gambert P, Lizard G, Neel D: 7-Ketocholesterol-induced apoptosis. Involvement of several pro-apoptotic but also anti-apoptotic calcium-dependent transduction pathways. FEBS J. 2005 Jun;272(12):3093-104. [15955068 ]
  8. Monier S, Samadi M, Prunet C, Denance M, Laubriet A, Athias A, Berthier A, Steinmetz E, Jurgens G, Negre-Salvayre A, Bessede G, Lemaire-Ewing S, Neel D, Gambert P, Lizard G: Impairment of the cytotoxic and oxidative activities of 7 beta-hydroxycholesterol and 7-ketocholesterol by esterification with oleate. Biochem Biophys Res Commun. 2003 Apr 11;303(3):814-24. [12670484 ]
  9. Lizard G, Moisant M, Cordelet C, Monier S, Gambert P, Lagrost L: Induction of similar features of apoptosis in human and bovine vascular endothelial cells treated by 7-ketocholesterol. J Pathol. 1997 Nov;183(3):330-8. [9422990 ]
  10. Tuomainen TP, Diczfalusy U, Kaikkonen J, Nyyssonen K, Salonen JT: Serum ferritin concentration is associated with plasma levels of cholesterol oxidation products in man. Free Radic Biol Med. 2003 Oct 15;35(8):922-8. [14556856 ]
  11. Scopesi F, Zunin P, Mazzella M, Testa M, Boggia R, Evangelisti F, Serra G: 7-ketocholesterol in human and adapted milk formulas. Clin Nutr. 2002 Oct;21(5):379-84. [12381334 ]
  12. Zhang Y, Yu C, Liu J, Spencer TA, Chang CC, Chang TY: Cholesterol is superior to 7-ketocholesterol or 7 alpha-hydroxycholesterol as an allosteric activator for acyl-coenzyme A:cholesterol acyltransferase 1. J Biol Chem. 2003 Mar 28;278(13):11642-7. Epub 2003 Jan 17. [12533546 ]
  13. Shimozawa M, Naito Y, Manabe H, Uchiyama K, Kuroda M, Katada K, Yoshida N, Yoshikawa T: 7-Ketocholesterol enhances the expression of adhesion molecules on human aortic endothelial cells by increasing the production of reactive oxygen species. Redox Rep. 2004;9(6):370-5. [15720835 ]
  14. Ghelli A, Porcelli AM, Zanna C, Rugolo M: 7-Ketocholesterol and staurosporine induce opposite changes in intracellular pH, associated with distinct types of cell death in ECV304 cells. Arch Biochem Biophys. 2002 Jun 15;402(2):208-17. [12051665 ]
  15. Martinet W, De Bie M, Schrijvers DM, De Meyer GR, Herman AG, Kockx MM: 7-ketocholesterol induces protein ubiquitination, myelin figure formation, and light chain 3 processing in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2004 Dec;24(12):2296-301. Epub 2004 Sep 30. [15458974 ]
  16. Hayden JM, Brachova L, Higgins K, Obermiller L, Sevanian A, Khandrika S, Reaven PD: Induction of monocyte differentiation and foam cell formation in vitro by 7-ketocholesterol. J Lipid Res. 2002 Jan;43(1):26-35. [11792719 ]
  17. Jessup W, Brown AJ: Novel routes for metabolism of 7-ketocholesterol. Rejuvenation Res. 2005 Spring;8(1):9-12. [15798369 ]
  18. Huang RF, Yaong HC, Chen SC, Lu YF: In vitro folate supplementation alleviates oxidative stress, mitochondria-associated death signalling and apoptosis induced by 7-ketocholesterol. Br J Nutr. 2004 Dec;92(6):887-94. [15613250 ]
  19. Kahn E, Vejux A, Lizard G, Bessede G, Frouin F, Prunet C, Bernengo JC, Brau F, Todd-Pokropek A, Gambert P: Analysis of the fluorescence of monodansylcadaverine-positive cytoplasmic structures during 7-ketocholesterol-induced cell death. Anal Quant Cytol Histol. 2004 Feb;26(1):47-56. [15032081 ]
  20. Kahn E, Vejux A, Dumas D, Montange T, Frouin F, Robert V, Riedinger JM, Stoltz JF, Gambert P, Todd-Pokropek A, Lizard G: FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol. Anal Quant Cytol Histol. 2004 Dec;26(6):304-13. [15678612 ]
  21. Lyons MA, Brown AJ: 7-Ketocholesterol. Int J Biochem Cell Biol. 1999 Mar-Apr;31(3-4):369-75. [10224662 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7-ketocholesterol to 7-beta-hydroxycholesterol (By similarity).
Gene Name:
HSD11B1
Uniprot ID:
P28845
Molecular weight:
32400.665