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Human Metabolome Database Version 2.5

 

Showing metabocard for 27-Hydroxycholesterol (HMDB02103)

Legend: metabolite field enzyme field

Version 2.5
Creation Date 2006-05-22 15:17:36
Update Date 2009-05-05 20:59:05
Accession Number HMDB02103
Secondary Accession Numbers Not Available
Common Name 27-Hydroxycholesterol
Description 27-hydroxycholesterol is an oxygenated derivative of cholesterol and a major oxysterol in circulation. 27-hydroxycholesterol is the product of the enzyme sterol 27-hydroxylase. The enzyme is critical for degradation of the steroid side-chain and a genetic deficiency of the enzyme leads to reduced formation of bile acids in humans. There is a correlation between 27-hydroxycholesterol and cholesterol in the circulation, and females have lower levels of 27-hydroxycholesterol than males. A strong correlation is observed between circulating levels of 27-hydroxycholesterol and cholesterol, in both healthy subjects and subjects with hypercholesterolemia and documented atherosclerosis. 27-hydroxycholesterol is metabolized by an oxysterol 7a-hydroxylase in the liver, and changes in the activity of this enzyme may lead to accumulation of 27-hydroxycholesterol in the circulation. It has been reported that patients with a genetic deficiency of oxysterol 7a-hydroxylase in the liver had markedly increased levels of 27-hydroxycholesterol in the circulation. Under normal conditions, however, and in the absence of liver or kidney disease, changes in the levels of 27-hydroxycholesterol in the circulation are likely to be caused by changes in the rate of synthesis of these steroids rather than by the rate of metabolism. Three possible explanations for the high concentrations of 27-hydroxycholesterol found in the circulation of the three subjects with atherosclerosis could be: 1) Increased expression of sterol 27-hydroxylase owing to a genetic factor or some other factor completely unrelated to atherosclerosis. 2) The extrahepatic sterol 27-hydroxylase may be up-regulated by circulating factors (e.g. cytokines) that are directly or indirectly related to the development of atherosclerosis. 3) The high amounts of cholesterol accumulating in macrophages in some patients with atherosclerosis may result in increased flux of 27-hydroxycholesterol from the macrophages to the circulation. Since there is a close relation between levels of cholesterol and 27-hydroxycholesterol in the circulation, the possibility must be considered that the flux of 27-hydroxycholesterol into the brain may be part of the yet unexplained link between hypercholesterolemia and Alzheimer's disease. 27-hydroxysterol is the most dominant oxysterol in human ateromas where it may reflect a mechanism for eliminating excessive cholesterol and thus have a protective role. Hypercholesterolemia and chronic low-grade immunological activation are pivotal in the development of atherosclerosis. However, the interconnections between these two factors are not well known. The CD40 system, as measured by the plasma level of soluble CD40 (sCD40), is associated with cholesterol metabolism in hypercholesterolemic patients. When combined, a decreased cholesterol synthesis rate and increased levels of 27-hydroxycholesterol may be a consequence of high levels of cellular cholesterol and, therefore, be related to sCD40. However, sCD40 had no significant correlation with total plasma cholesterol. This suggests that the cellular cholesterol synthesis rate and 27-hydroxycholesterol production are more importantly linked with the plasma levels of sCD40 than total cholesterol. (PMID: 16081359, 17012138, 11504730, 9144161)
Synonyms
  1. (25R)-26-Hydroxycholesterol
  2. (25R)-Cholest-5-ene-3b,26-diol
  3. (25R)-Cholest-5-ene-3beta,26-diol
  4. (3-beta)-cholest-5-ene-3,26-diol
  5. (3b,25R)-Cholest-5-ene-3,26-diol
  6. (3beta,25R)-Cholest-5-ene-3,26,diol
  7. 26-hydroxycholesterol(25R)
  8. Cholest-5-ene-3-beta,26-diol
  9. Cholest-5-ene-3beta,26-diol
  10. Cholest-5-ene-3beta,27-diol
  11. cholest-(25R)-5-en-3beta,26-diol
  12. Cholest-5-ene-3-beta,27-diol
  13. Cholest-5-ene-3-b,27-diol
Chemical IUPAC Name (3S,8S,9S,10R,13R,14S,17R)-17-[(2R)-7-hydroxy-6-methyl-heptan-2-yl]-10,13-d
Chemical Formula C27H46O2
Chemical Structure Structure
Chemical Taxonomy
Kingdom
  • Organic
Super Class
  • Cholesterols and derivatives
Class
  • Steroids and Steroid Derivatives
Sub Class
  • Dihydroxy steroids
Family
  • Mammalian Metabolite
Species
  • primary alcohol
  • secondary alcohol
  • alkene
Biofunction
  • Hormones, Membrane component
Application
—
Source
  • Endogenous
Average Molecular Weight 402.653
Monoisotopic Molecular Weight 402.349792
Isomeric SMILES C[C@@H](CO)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Canonical SMILES CC(CO)CCCC(C)C1CCC2C3CC=C4CC(O)CCC4(C)C3CCC12C
KEGG Compound ID C06340 Link Image
BioCyc ID 27-HYDROXYCHOLESTEROL Link Image
BiGG ID 48021 Link Image
Wikipedia Link Not Available
NuGOwiki Link HMDB02103 Link Image
Metagene Link HMDB02103 Link Image
METLIN ID 6487 Link Image
PubChem Compound 99470 Link Image
PubChem Substance 7850685 Link Image
ChEBI ID 16546 Link Image
CAS Registry Number 20380-11-4
InChI Identifier InChI=1/C27H46O2/c1-18(17-28)6-5-7-19(2)23-10-11-24-22-9-8-20-16-21(29)12-14-26(20,3)25(22)13-15-27(23,24)4/h8,18-19,21-25,28-29H,5-7,9-17H2,1-4H3/t18-,19-,21+,22+,23-,24+,25+,26+,27-/m1/s1
Synthesis Reference Hausheer, Frederick H.; Haridas, Kochat. Process for preparing 27-hydroxycholesterol and related derivatives. PCT Int. Appl. (1997), 38 pp.
Melting Point (Experimental) Not Available
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 2.11e-04 mg/mL [Predicted by ALOGPS] Calculated using ALOGPS
Physiological Charge 0
State Solid
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP/Hydrophobicity 6.21 [Predicted by ALOGPS]; 6.6 [Predicted by PubChem via XLOGP] Calculated using ALOGPS
Material Safety Data Sheet (MSDS) Not Available
MOL File Show
SDF File Show
PDB File Show
2D Structure
3D Structure
Experimental PDB ID Not Available
Experimental 1H NMR Spectrum Not Available
Experimental 13C NMR Spectrum Not Available
Experimental 13C HSQC Spectrum Not Available
Predicted 1H NMR Spectrum Show Image
Show Peaklist
Predicted 13C NMR Spectrum Show Image
Show Peaklist
Mass Spectrum Not Available
Simplified TOCSY Spectrum Not Available
BMRB Spectrum Not Available
Cellular Location
  • Membrane (Predicted from LogP)
  • endoplasmic reticulum
  • mitochondria
Biofluid Location
  • Blood
  • Cerebrospinal Fluid
Tissue Location
Tissue References
Brain —
Fibroblasts —
Neuron —
Concentrations (Normal)
Biofluid Blood
Value 0.3 +/- 0.074 uM
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
  • Burkard I, Rentsch KM, von Eckardstein A: Determination of 24S- and 27-hydroxycholesterol in plasma by high-performance liquid chromatography-mass spectrometry. J Lipid Res. 2004 Apr;45(4):776-81. Epub 2004 Jan 16. [PubMed Link Image]
Biofluid CSF
Value 0.0013 +/- 0.0001 uM
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
  • Leoni V, Masterman T, Mousavi FS, Wretlind B, Wahlund LO, Diczfalusy U, Hillert J, Bjorkhem I: Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004 Feb;42(2):186-91. [PubMed Link Image]
Biofluid CSF
Value 0.002 +/- 0.0004 uM
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
  • 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. [PubMed Link Image]
Concentrations (Abnormal)
Biofluid CSF
Value 0.0026 +/- 0.0002 uM
Age Adult:>18 yrs old
Sex Both
Condition Multiple sclerosis
Comments With gadolinium-enhancing lesion
References
  • Leoni V, Masterman T, Mousavi FS, Wretlind B, Wahlund LO, Diczfalusy U, Hillert J, Bjorkhem I: Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004 Feb;42(2):186-91. [PubMed Link Image]
Biofluid CSF
Value 0.0038 +/- 0.0003 uM
Age Elderly:>65 yrs old
Sex Both
Condition Alzheimer's disease
Comments Not Available
References
  • Leoni V, Masterman T, Mousavi FS, Wretlind B, Wahlund LO, Diczfalusy U, Hillert J, Bjorkhem I: Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004 Feb;42(2):186-91. [PubMed Link Image]
Biofluid CSF
Value 0.01 +/- 0.001 uM
Age Adult:>18 yrs old
Sex Both
Condition Demyelinating polyneuropathy
Comments Not Available
References
  • Leoni V, Masterman T, Mousavi FS, Wretlind B, Wahlund LO, Diczfalusy U, Hillert J, Bjorkhem I: Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004 Feb;42(2):186-91. [PubMed Link Image]
Biofluid CSF
Value 0.0058 +/- 0.0006 uM
Age Adult:>18 yrs old
Sex Both
Condition Subarachnoid hemorrhage
Comments Not Available
References
  • Leoni V, Masterman T, Mousavi FS, Wretlind B, Wahlund LO, Diczfalusy U, Hillert J, Bjorkhem I: Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004 Feb;42(2):186-91. [PubMed Link Image]
Biofluid CSF
Value 0.006 +/- 0.0006 uM
Age Adult:>18 yrs old
Sex Both
Condition Meningitis
Comments Viral
References
  • Leoni V, Masterman T, Mousavi FS, Wretlind B, Wahlund LO, Diczfalusy U, Hillert J, Bjorkhem I: Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004 Feb;42(2):186-91. [PubMed Link Image]
Biofluid CSF
Value 0.0063 +/- 0.001 uM
Age Adult:>18 yrs old
Sex Both
Condition Neuroborreliosis
Comments Not Available
References
  • Leoni V, Masterman T, Mousavi FS, Wretlind B, Wahlund LO, Diczfalusy U, Hillert J, Bjorkhem I: Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004 Feb;42(2):186-91. [PubMed Link Image]
Biofluid CSF
Value 0.0045 +/- 0.001 uM
Age Elderly:>65 yrs old
Sex Both
Condition Mild cognitive impairment
Comments Also known as incipient dementia or isolated memory impairment
References
  • Leoni V, Shafaati M, Salomon A, Kivipelto M, Bjorkhem I, Wahlund LO: Are the CSF levels of 24S-hydroxycholesterol a sensitive biomarker for mild cognitive impairment? Neurosci Lett. 2006 Apr 10-17;397(1-2):83-7. Epub 2006 Jan 6. [PubMed Link Image]
Biofluid CSF
Value 0.003 +/- 0.0008 uM
Age Adult:>18 yrs old
Sex Both
Condition Multiple sclerosis
Comments Not Available
References
  • 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. [PubMed Link Image]
Associated Disorders
Condition References
Alzheimer's disease
  • Leoni V, Masterman T, Mousavi FS, Wretlind B, Wahlund LO, Diczfalusy U, Hillert J, Bjorkhem I: Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004 Feb;42(2):186-91. [PubMed Link Image]
Demyelinating polyneuropathy
  • Leoni V, Masterman T, Mousavi FS, Wretlind B, Wahlund LO, Diczfalusy U, Hillert J, Bjorkhem I: Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004 Feb;42(2):186-91. [PubMed Link Image]
Meningitis
  • Leoni V, Masterman T, Mousavi FS, Wretlind B, Wahlund LO, Diczfalusy U, Hillert J, Bjorkhem I: Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004 Feb;42(2):186-91. [PubMed Link Image]
Mild cognitive impairment
  • Leoni V, Shafaati M, Salomon A, Kivipelto M, Bjorkhem I, Wahlund LO: Are the CSF levels of 24S-hydroxycholesterol a sensitive biomarker for mild cognitive impairment? Neurosci Lett. 2006 Apr 10-17;397(1-2):83-7. Epub 2006 Jan 6. [PubMed Link Image]
Multiple sclerosis
Neuroborreliosis
  • Leoni V, Masterman T, Mousavi FS, Wretlind B, Wahlund LO, Diczfalusy U, Hillert J, Bjorkhem I: Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004 Feb;42(2):186-91. [PubMed Link Image]
Subarachnoid hemorrhage
  • Leoni V, Masterman T, Mousavi FS, Wretlind B, Wahlund LO, Diczfalusy U, Hillert J, Bjorkhem I: Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004 Feb;42(2):186-91. [PubMed Link Image]
OMIM ID
Pathways
Name SMPDB Link KEGG Link
Bile Acid Biosynthesis SMP00035 Link Image map00120 Link Image
General References
  1. Burkard I, Rentsch KM, von Eckardstein A: Determination of 24S- and 27-hydroxycholesterol in plasma by high-performance liquid chromatography-mass spectrometry. J Lipid Res. 2004 Apr;45(4):776-81. Epub 2004 Jan 16. [PubMed Link Image]
  2. Fu X, Menke JG, Chen Y, Zhou G, MacNaul KL, Wright SD, Sparrow CP, Lund EG: 27-hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells. J Biol Chem. 2001 Oct 19;276(42):38378-87. Epub 2001 Aug 14. [PubMed Link Image]
  3. Rajagopalon I, Kok E, Cohen BI, Javitt NB: 26-Hydroxycholesterol disulfate: metabolism and excretion in the normal neonate. J Steroid Biochem. 1986 Dec;25(6):991-4. [PubMed Link Image]
  4. Li S, Pang J, Jackson EM, Wilson WK, Mott GE, Schroepfer GJ Jr: Kinetics and plasma concentrations of 26-hydroxycholesterol in baboons. Biochim Biophys Acta. 2000 May 31;1485(2-3):173-84. [PubMed Link Image]
  5. Frolov A, Zielinski SE, Crowley JR, Dudley-Rucker N, Schaffer JE, Ory DS: NPC1 and NPC2 regulate cellular cholesterol homeostasis through generation of low density lipoprotein cholesterol-derived oxysterols. J Biol Chem. 2003 Jul 11;278(28):25517-25. Epub 2003 Apr 28. [PubMed Link Image]
  6. Brown J 3rd, Theisler C, Silberman S, Magnuson D, Gottardi-Littell N, Lee JM, Yager D, Crowley J, Sambamurti K, Rahman MM, Reiss AB, Eckman CB, Wolozin B: Differential expression of cholesterol hydroxylases in Alzheimer's disease. J Biol Chem. 2004 Aug 13;279(33):34674-81. Epub 2004 May 17. [PubMed Link Image]
  7. Leoni V, Masterman T, Mousavi FS, Wretlind B, Wahlund LO, Diczfalusy U, Hillert J, Bjorkhem I: Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004 Feb;42(2):186-91. [PubMed Link Image]
  8. Bellosta S, Corsini A, Bernini F, Granata A, Didoni G, Mazzotti M, Fumagalli R: 27-Hydroxycholesterol modulation of low density lipoprotein metabolism in cultured human hepatic and extrahepatic cells. FEBS Lett. 1993 Oct 11;332(1-2):115-8. [PubMed Link Image]
  9. Heverin M, Bogdanovic N, Lutjohann D, Bayer T, Pikuleva I, Bretillon L, Diczfalusy U, Winblad B, Bjorkhem I: Changes in the levels of cerebral and extracerebral sterols in the brain of patients with Alzheimer's disease. J Lipid Res. 2004 Jan;45(1):186-93. Epub 2003 Oct 1. [PubMed Link Image]
  10. Shoda J, Toll A, Axelson M, Pieper F, Wikvall K, Sjovall J: Formation of 7 alpha- and 7 beta-hydroxylated bile acid precursors from 27-hydroxycholesterol in human liver microsomes and mitochondria. Hepatology. 1993 Mar;17(3):395-403. [PubMed Link Image]
  11. Goldman M, Vlahcevic ZR, Schwartz CC, Gustafsson J, Swell L: Bile acid metabolism in cirrhosis. VIII. Quantitative evaluation of bile acid synthesis from [7 beta-3H]7 alpha-hydroxycholesterol and [G-3H]26-hydroxycholesterol. Hepatology. 1982 Jan-Feb;2(1):59-66. [PubMed Link Image]
  12. Summerfield JA, Billing BH, Shackleton CH: Identification of bile acids in the serum and urine in cholestasis. Evidence for 6alpha-hydroxylation of bile acids in man. Biochem J. 1976 Feb 15;154(2):507-16. [PubMed Link Image]
  13. Lala DS, Syka PM, Lazarchik SB, Mangelsdorf DJ, Parker KL, Heyman RA: Activation of the orphan nuclear receptor steroidogenic factor 1 by oxysterols. Proc Natl Acad Sci U S A. 1997 May 13;94(10):4895-900. [PubMed Link Image]
  14. Norlin M, Andersson U, Bjorkhem I, Wikvall K: Oxysterol 7 alpha-hydroxylase activity by cholesterol 7 alpha-hydroxylase (CYP7A). J Biol Chem. 2000 Nov 3;275(44):34046-53. [PubMed Link Image]