27-Hydroxycholesterol
27-hydroxycholesterol is an oxygenated derivative of cholesterol and a major oxysterol in circliation. 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 circliation, and females have lower levels of 27-hydroxycholesterol than males. A strong correlation is observed between circliating 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 accumliation of 27-hydroxycholesterol in the circliation. 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 circliation. Under normal conditions, however, and in the absence of liver or kidney disease, changes in the levels of 27-hydroxycholesterol in the circliation 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 circliation of the three subjects with atherosclerosis colid 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-regliated by circliating factors (e.g. cytokines) that are directly or indirectly related to the development of atherosclerosis. 3) The high amounts of cholesterol accumliating in macrophages in some patients with atherosclerosis may reslit in increased flux of 27-hydroxycholesterol from the macrophages to the circliation. Since there is a close relation between levels of cholesterol and 27-hydroxycholesterol in the circliation, 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 Alzheimers 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 cellliar cholesterol and, therefore, be related to sCD40. However, sCD40 had no significant correlation with total plasma cholesterol. This suggests that the cellliar 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 ).
Structure for HMDB02103 (27-Hydroxycholesterol)
C27H46O2
402.6529
402.349780716
(1S,2R,5S,10S,11S,14R,15R)-14-[(2R,6R)-7-hydroxy-6-methylheptan-2-yl]-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-7-en-5-ol
(25R)-26-hydroxycholesterol
20380-11-4
FYHRJWMENCALJY-YSQMORBQSA-N
Not classified
Detected and Quantified
Solid
Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available
Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available
Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available
Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available
Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available
Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available
Mlitiple sclerosis
Meningitis
Mild cognitive impairment
- 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:15061359 ]
- 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:15061359 ]
- 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:15061359 ]
- 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:15061359 ]
- 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:16406316 ]
- 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:15061359 ]
- Leoni V, Lutjohann D, Masterman T: Levels of 7-oxocholesterol in cerebrospinal fluid are more than one thousand times lower than reported in mlitiple sclerosis. J Lipid Res. 2005 Feb;46(2):191-5. Epub 2004 Dec 1. [PubMed:15576852 ]
- 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:15061359 ]
Not Available
Not Available
Not Available
Not Available
FDB022846
Not Available
110495
C06340
27-HYDROXYCHOLESTEROL
48021
Not Available
HMDB02103
HMDB02103
6487
123976
Not Available
387060
Product: Dextrorotation nimorazole phosphate ester
- 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:938463 ]
- 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:15061359 ]
- 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:14729854 ]
- 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:11504730 ]
- 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:3795956 ]
- 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:10832098 ]
- 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:12719428 ]
- 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 Alzheimers disease. J Biol Chem. 2004 Aug 13;279(33):34674-81. Epub 2004 May 17. [PubMed:15148325 ]
- 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:8405424 ]
- 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 Alzheimers disease. J Lipid Res. 2004 Jan;45(1):186-93. Epub 2003 Oct 1. [PubMed:14523054 ]
- 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:8444412 ]
- 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:7054068 ]
- 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:9144161 ]
- 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:10882719 ]
- Babiker A, Dzeletovic S, Wiklund B, Pettersson N, Salonen J, Nyyssonen K, Eriksson M, Diczfalusy U, Bjorkhem I: Patients with atherosclerosis may have increased circulating levels of 27-hydroxycholesterol and cholestenoic acid. Scand J Clin Lab Invest. 2005;65(5):365-75. [PubMed:16081359 ]
- Luomala M, Paiva H, Laaksonen R, Thelen K, Lutjohann D, Peltonen N, Lehtimaki T: Plasma-soluble CD40 is related to cholesterol metabolism in patients with moderate hypercholesterolemia. Scand Cardiovasc J. 2006 Oct;40(5):280-4. [PubMed:17012138 ]
Enzymes
- General function:
- Involved in monooxygenase activity
- Specific function:
- Catalyzes a rate-limiting step in cholesterol catabolism and bile acid biosynthesis by introducing a hydrophilic moiety at position 7 of cholesterol. Important for cholesterol homeostasis.
- Gene Name:
- CYP7A1
- Uniprot ID:
- P22680
- Molecular weight:
- 57660.155
Reactions
- General function:
- Involved in monooxygenase activity
- Specific function:
- Catalyzes the first step in the oxidation of the side chain of sterol intermediates; the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol. Has also a vitamin D3-25-hydroxylase activity.
- Gene Name:
- CYP27A1
- Uniprot ID:
- Q02318
- Molecular weight:
- 60234.28
Reactions
- General function:
- Involved in monooxygenase activity
- Specific function:
- Not Available
- Gene Name:
- CYP7B1
- Uniprot ID:
- O75881
- Molecular weight:
- 58255.325