1.0 2011-09-21 00:08:11 UTC 2015-10-09 22:29:05 UTC FDB022079 7-Ketocholesterol 7-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) [HMDB] 3b-Hydroxycholest-5-en-7-one 7-Ketocholesterol 7-Oxocholesterol Cholest-5-en-3b-ol-7-one delta5-Cholesten-3b-ol-7-one C27H44O2 400.6371 400.334130652 (1S,2R,10S,11S,15R)-5-hydroxy-2,15-dimethyl-14-[(2R)-6-methylheptan-2-yl]tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-7-en-9-one (1S,2R,10S,11S,15R)-5-hydroxy-2,15-dimethyl-14-[(2R)-6-methylheptan-2-yl]tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-7-en-9-one 566-28-9 [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=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 YIKKMWSQVKJCOP-QJFKPLHKSA-N belongs to the class of organic compounds known as cholesterols and derivatives. Cholesterols and derivatives are compounds containing a 3-hydroxylated cholestane core. Cholesterols and derivatives Organic compounds Lipids and lipid-like molecules Steroids and steroid derivatives Cholestane steroids Aliphatic homopolycyclic compounds 3-hydroxy delta-5-steroids 7-oxosteroids Cyclic alcohols and derivatives Cyclohexenones Delta-5-steroids Hydrocarbon derivatives Organic oxides Secondary alcohols 3-hydroxy-delta-5-steroid 3-hydroxysteroid 7-oxosteroid Alcohol Aliphatic homopolycyclic compound Carbonyl group Cholesterol Cholesterol-skeleton Cyclic alcohol Cyclohexenone Delta-5-steroid Hydrocarbon derivative Hydroxysteroid Ketone Organic oxide Organic oxygen compound Organooxygen compound Oxosteroid Secondary alcohol Solid logp 5.80 ALOGPS logs -6.29 ALOGPS solubility 2.08e-04 g/l ALOGPS logp 6.55 ChemAxon pka_strongest_acidic 17.39 ChemAxon pka_strongest_basic -1.4 ChemAxon iupac (1S,2R,10S,11S,15R)-5-hydroxy-2,15-dimethyl-14-[(2R)-6-methylheptan-2-yl]tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-7-en-9-one ChemAxon average_mass 400.6371 ChemAxon mono_mass 400.334130652 ChemAxon 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 ChemAxon formula C27H44O2 ChemAxon inchi 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 ChemAxon inchikey YIKKMWSQVKJCOP-QJFKPLHKSA-N ChemAxon polar_surface_area 37.3 ChemAxon refractivity 121.26 ChemAxon polarizability 50.9 ChemAxon rotatable_bond_count 5 ChemAxon acceptor_count 2 ChemAxon donor_count 1 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Specdb::NmrOneD 1395 Specdb::NmrTwoD 1339 Specdb::CMs 17705 Specdb::CMs 37575 Specdb::CMs 171438 Specdb::CMs 1064196 Specdb::CMs 1064198 Specdb::CMs 1064200 Specdb::MsMs 719 Specdb::MsMs 720 Specdb::MsMs 721 Specdb::MsMs 305197 Specdb::MsMs 305198 Specdb::MsMs 305199 Specdb::MsMs 348550 Specdb::MsMs 348551 Specdb::MsMs 348552 Specdb::MsMs 2658592 Specdb::MsMs 2658593 Specdb::MsMs 2658594 Specdb::MsMs 3050588 Specdb::MsMs 3050589 Specdb::MsMs 3050590 HMDB00501 #<Reference:0x000055ce2ecd1890> #<Reference:0x000055ce2ecd16b0> #<Reference:0x000055ce2ecd14a8> #<Reference:0x000055ce2ecd12a0> #<Reference:0x000055ce2ecd1070> #<Reference:0x000055ce2ecd0d00> #<Reference:0x000055ce2ecd0aa8> #<Reference:0x000055ce2ecd0760> #<Reference:0x000055ce2ecd0558> #<Reference:0x000055ce2ecd0378> #<Reference:0x000055ce2ecd01c0> #<Reference:0x000055ce2ecd0008> #<Reference:0x000055ce2ecc3e48> #<Reference:0x000055ce2ecc3bc8> #<Reference:0x000055ce2ecc38a8> #<Reference:0x000055ce2ecc34c0> #<Reference:0x000055ce2ecc1508> #<Reference:0x000055ce2ecbf9b0> #<Reference:0x000055ce2ecbf3e8> #<Reference:0x000055ce2ecbedd0> #<Reference:0x000055ce2ecbead8> Anatidae Type 1 specific Anatidae 8830 Beefalo Type 1 specific Bos taurus X Bison bison 297284 Bison Type 1 specific Bison bison 9901 Buffalo Type 1 specific Bubalus bubalis 89462 Cattle (Beef, Veal) Type 1 specific Bos taurus 9913 Chicken Type 1 specific Gallus gallus 9031 Columbidae (Dove, Pigeon) Type 1 specific Columbidae 8930 Deer Type 1 specific Cervidae 9850 Domestic goat Type 1 specific Capra aegagrus hircus 9925 Domestic pig Type 1 specific Sus scrofa domestica 9825 Elk Type 1 specific Cervus canadensis 1574408 Emu Type 1 specific Dromaius novaehollandiae 8790 European rabbit Type 1 specific Oryctolagus 9984 Greylag goose Type 1 specific Anser anser 8843 Guinea hen Type 1 specific Numida meleagris 8996 Horse Type 1 specific Equus caballus 9796 Mallard duck Type 1 specific Anas platyrhynchos 8839 Mountain hare Type 1 specific Lepus timidus 62621 Mule deer Type 1 specific Odocoileus 9871 Ostrich Type 1 specific Struthio camelus 8801 Pheasant Type 1 specific Phasianus colchicus 9054 Quail Type 1 specific Phasianidae 9005 Rabbit Type 1 specific Leporidae 9979 Rock ptarmigan Type 1 specific Lagopus muta 64668 Sheep (Mutton, Lamb) Type 1 specific Ovis aries 9940 Squab Type 1 specific Columba 8931 Turkey Type 1 specific Meleagris gallopavo 9103 Velvet duck Type 1 specific Melanitta fusca 371864 Wild boar Type 1 specific Sus scrofa 9823 Corticosteroid 11-beta-dehydrogenase isozyme 1 P28845 HSD11B1