WordNet
- any of a group of natural steroid alcohols derived from plants or animals; they are waxy insoluble substances (同)steroid alcohol
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2013/12/22 15:27:27」(JST)
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Cytochrome P450, family 27, subfamily A, polypeptide 1 |
Available structures |
PDB |
Ortholog search: PDBe, RCSB |
List of PDB id codes |
1MFX
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Identifiers |
Symbols |
CYP27A1; CP27; CTX; CYP27 |
External IDs |
OMIM: 606530 MGI: 88594 HomoloGene: 36040 ChEMBL: 5992 GeneCards: CYP27A1 Gene |
EC number |
1.14.13.15 |
Gene Ontology |
Molecular function |
• iron ion binding
• steroid hydroxylase activity
• electron carrier activity
• heme binding
• vitamin D3 25-hydroxylase activity
• cholesterol 26-hydroxylase activity
• cholestanetriol 26-monooxygenase activity
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Cellular component |
• mitochondrial inner membrane
• mitochondrial matrix
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Biological process |
• bile acid biosynthetic process
• xenobiotic metabolic process
• cholesterol metabolic process
• bile acid metabolic process
• small molecule metabolic process
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Sources: Amigo / QuickGO |
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RNA expression pattern |
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More reference expression data |
Orthologs |
Species |
Human |
Mouse |
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Entrez |
1593 |
104086 |
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Ensembl |
ENSG00000135929 |
ENSMUSG00000026170 |
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UniProt |
Q02318 |
Q9DBG1 |
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RefSeq (mRNA) |
NM_000784 |
NM_024264 |
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RefSeq (protein) |
NP_000775 |
NP_077226 |
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Location (UCSC) |
Chr 2:
219.65 – 219.68 Mb |
Chr 1:
74.71 – 74.74 Mb |
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PubMed search |
[1] |
[2] |
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CYP27A1 is a gene encoding a cytochrome P450 oxidase, and is commonly known as sterol 27-hydroxylase. This enzyme is located in many different tissues where it is found within the mitochondria. It is most prominently involved in the biosynthesis of bile acids.
Contents
- 1 Function
- 2 Clinical significance
- 3 Interactive pathway map
- 4 References
- 5 Further reading
- 6 External links
Function[edit]
CYP27A1 participates in the degradation of cholesterol to bile acids in both the classic and acidic pathways.[1] It is the initiating enzyme in the acidic pathway to bile acids, yielding oxysterols by introducing a hydroxyl group to the carbon at the 27 position in cholesterol. In the acidic pathway, it produces 27-hydroxycholesterol from cholesterol whereas in the classic or neutral pathway, it produces 3β-hydroxy-5-cholestenoic acid.
It is also involved in the metabolism of vitamin D3.[2]
While CYP27A1 is present in many different tissues, its function in these tissues is largely uncharacterized. In macrophages, 27-hydroxycholesterol generated by this enzyme may be helpful against the production of inflammatory factors associated with cardiovascular disease.[3]
Clinical significance[edit]
Mutations in CYP27A1 are associated with cerebrotendineous xanthomatosis, a rare lipid storage disease.
Interactive pathway map[edit]
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
Vitamin D Synthesis Pathway edit
- ^ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".
References[edit]
- ^ Chiang JY (February 1998). "Regulation of bile acid synthesis". Front Biosci 3: d176–193. PMID 9450986.
- ^ Sakaki T, Kagawa N, Yamamoto K, Inouye K (January 2005). "Metabolism of vitamin D3 by cytochromes P450". Front. Biosci. 10: 119–34. PMID 15574355.
- ^ Taylor JM, Borthwick F, Bartholomew C, Graham A (June 2010). "Overexpression of steroidogenic acute regulatory protein increases macrophage cholesterol efflux to apolipoprotein AI". Cardiovasc Res 86 (3): 526–534. doi:10.1093/cvr/cvq015. PMID 20083572.
Further reading[edit]
- Cali JJ, Russell DW (1991). "Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis.". J. Biol. Chem. 266 (12): 7774–8. PMID 1708392.
- Cali JJ, Hsieh CL, Francke U, Russell DW (1991). "Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis.". J. Biol. Chem. 266 (12): 7779–83. PMID 2019602.
- Guo YD, Strugnell S, Back DW, Jones G (1993). "Transfected human liver cytochrome P-450 hydroxylates vitamin D analogs at different side-chain positions.". Proc. Natl. Acad. Sci. U.S.A. 90 (18): 8668–72. doi:10.1073/pnas.90.18.8668. PMC 47419. PMID 7690968.
- Kim KS, Kubota S, Kuriyama M et al. (1994). "Identification of new mutations in sterol 27-hydroxylase gene in Japanese patients with cerebrotendinous xanthomatosis (CTX)". J. Lipid Res. 35 (6): 1031–9. PMID 7915755.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Leitersdorf E, Reshef A, Meiner V et al. (1993). "Frameshift and splice-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis in Jews or Moroccan origin". J. Clin. Invest. 91 (6): 2488–96. doi:10.1172/JCI116484. PMC 443309. PMID 8514861.
- Chen W, Kubota S, Kim KS et al. (1997). "Novel homozygous and compound heterozygous mutations of sterol 27-hydroxylase gene (CYP27) cause cerebrotendinous xanthomatosis in three Japanese patients from two unrelated families". J. Lipid Res. 38 (5): 870–9. PMID 9186905.
- Reiss AB, Martin KO, Rojer DE et al. (1997). "Sterol 27-hydroxylase: expression in human arterial endothelium". J. Lipid Res. 38 (6): 1254–60. PMID 9215552.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Chen W, Kubota S, Ujike H et al. (1998). "A novel Arg362Ser mutation in the sterol 27-hydroxylase gene (CYP27): its effects on pre-mRNA splicing and enzyme activity". Biochemistry 37 (43): 15050–6. doi:10.1021/bi9807660. PMID 9790667.
- Shiga K, Fukuyama R, Kimura S et al. (1999). "Mutation of the sterol 27-hydroxylase gene (CYP27) results in truncation of mRNA expressed in leucocytes in a Japanese family with cerebrotendinous xanthomatosis". J. Neurol. Neurosurg. Psychiatr. 67 (5): 675–7. doi:10.1136/jnnp.67.5.675. PMC 1736608. PMID 10519880.
- Gascon-Barré M, Demers C, Ghrab O et al. (2001). "Expression of CYP27A, a gene encoding a vitamin D-25 hydroxylase in human liver and kidney". Clin. Endocrinol. (Oxf) 54 (1): 107–15. doi:10.1046/j.1365-2265.2001.01160.x. PMID 11167933.
- Johnston TP, Nguyen LB, Chu WA, Shefer S (2001). "Potency of select statin drugs in a new mouse model of hyperlipidemia and atherosclerosis". International journal of pharmaceutics 229 (1–2): 75–86. doi:10.1016/S0378-5173(01)00834-1. PMID 11604260.
- Toba H, Fukuyama R, Sasaki M et al. (2002). "A Japanese patient with cerebrotendinous xanthomatosis has different mutations within two functional domains of CYP27". Clin. Genet. 61 (1): 77–8. doi:10.1034/j.1399-0004.2002.610116.x. PMID 11903362.
- Lamon-Fava S, Schaefer EJ, Garuti R et al. (2002). "Two novel mutations in the sterol 27-hydroxylase gene causing cerebrotendinous xanthomatosis". Clin. Genet. 61 (3): 185–91. doi:10.1034/j.1399-0004.2002.610303.x. PMID 12000359.
- Björkhem I, Araya Z, Rudling M et al. (2002). "Differences in the regulation of the classical and the alternative pathway for bile acid synthesis in human liver. No coordinate regulation of CYP7A1 and CYP27A1". J. Biol. Chem. 277 (30): 26804–7. doi:10.1074/jbc.M202343200. PMID 12011083.
- von Bahr S, Movin T, Papadogiannakis N et al. (2002). "Mechanism of accumulation of cholesterol and cholestanol in tendons and the role of sterol 27-hydroxylase (CYP27A1)". Arterioscler. Thromb. Vasc. Biol. 22 (7): 1129–35. doi:10.1161/01.ATV.0000022600.61391.A5. PMID 12117727.
- Meir K, Kitsberg D, Alkalay I et al. (2002). "Human sterol 27-hydroxylase (CYP27) overexpressor transgenic mouse model. Evidence against 27-hydroxycholesterol as a critical regulator of cholesterol homeostasis". J. Biol. Chem. 277 (37): 34036–41. doi:10.1074/jbc.M201122200. PMID 12119285.
- Lee MJ, Huang YC, Sweeney MG et al. (2002). "Mutation of the sterol 27-hydroxylase gene ( CYP27A1) in a Taiwanese family with cerebrotendinous xanthomatosis". J. Neurol. 249 (9): 1311–2. doi:10.1007/s00415-002-0762-9. PMID 12242561.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
External links[edit]
- GeneReviews/NCBI/NIH/UW entry on Cerebrotendinous Xanthomatosis
- Cytochrome P-450 CYP27A1 at the US National Library of Medicine Medical Subject Headings (MeSH)
Metabolism: lipid metabolism – ketones/cholesterol synthesis enzymes/steroid metabolism
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Mevalonate pathway |
To HMG-CoA |
- Acetyl-Coenzyme A acetyltransferase
- HMG-CoA synthase (regulated step)
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Ketogenesis |
- HMG-CoA lyase
- 3-hydroxybutyrate dehydrogenase
- Thiophorase
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To Mevalonic acid |
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To DMAPP |
- Mevalonate kinase
- Phosphomevalonate kinase
- Pyrophosphomevalonate decarboxylase
- Isopentenyl-diphosphate delta isomerase
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Geranyl- |
- Dimethylallyltranstransferase
- Geranyl pyrophosphate
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To cholesterol |
To lanosterol |
- Farnesyl-diphosphate farnesyltransferase
- Squalene monooxygenase
- Lanosterol synthase
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7-Dehydrocholesterol path |
- Lanosterol 14α-demethylase
- Sterol-C5-desaturase-like
- 7-Dehydrocholesterol reductase
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Desmosterol path |
- 24-dehydrocholesterol reductase
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To Bile acids |
- Cholesterol 7α-hydroxylase
- Sterol 27-hydroxylase
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Steroidogenesis |
To pregnenolone |
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To corticosteroids |
- aldosterone: 18-hydroxylase
- cortisol/cortisone: 17α-hydroxylase
- 11β dehydrogenase
- both: 3β dehydrogenase
- 21α-hydroxylase
- 11β-hydroxylase
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To sex hormones |
To androgens |
- 17α-hydroxylase/17,20 lyase
- 3β dehydrogenase
- 17β dehydrogenase
- 5α reductase
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To estrogens |
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Other/ungrouped |
- Steroid metabolism: sulfatase
- sulfotransferase
- Steroidogenic acute regulatory protein
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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noco (d)/cong/tumr, sysi/epon
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proc, drug (A10/H1/H2/H3/H5)
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Metabolism of vitamins, coenzymes, and cofactors
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Fat soluble vitamins |
Vitamin A
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Vitamin E
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- Alpha-tocopherol transfer protein
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Vitamin D
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- liver (Sterol 27-hydroxylase or CYP27A1)
- renal (25-Hydroxyvitamin D3 1-alpha-hydroxylase or CYP27B1)
- degradation (1,25-Dihydroxyvitamin D3 24-hydroxylase or CYP24A1)
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Vitamin K
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- Vitamin K epoxide reductase
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Water soluble vitamins |
Thiamine (B1)
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Niacin (B3)
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- Indoleamine 2,3-dioxygenase
- Formamidase
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Pantothenic acid (B5)
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Folic acid (B9)
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- Dihydropteroate synthase
- Dihydrofolate reductase
- Serine hydroxymethyltransferase
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- Methylenetetrahydrofolate reductase
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Vitamin B12
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Vitamin C
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Riboflavin (B2)
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Nonvitamin cofactors |
Tetrahydrobiopterin
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- GTP cyclohydrolase I
- 6-pyruvoyltetrahydropterin synthase
- Sepiapterin reductase
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Molybdenum cofactor
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noco, nuvi, sysi/epon, met
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Cytochromes, oxygenases: cytochrome P450 (EC 1.14)
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CYP1 |
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CYP2 |
- A6
- A7
- A13
- B6
- C8
- C9
- C18
- C19
- D6
- E1
- F1
- J2
- R1
- S1
- U1
- W1
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CYP3 (CYP3A) |
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CYP4 |
- A11
- A22
- B1
- F2
- F3
- F8
- F11
- F12
- F22
- V2
- X1
- Z1
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CYP5-20 |
- CYP5 (A1)
- CYP7 (A1, B1)
- CYP8 (A1, B1)
- CYP11 (A1, B1, B2)
- CYP17 (A1)
- CYP19 (A1)
- CYP20 (A1)
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CYP21-51 |
- CYP21 (A2)
- CYP24 (A1)
- CYP26 (A1, B1, C1)
- CYP27 (A1, B1, C1)
- CYP39 (A1)
- CYP46 (A1)
- CYP51 (A1)
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UpToDate Contents
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English Journal
- Plasma 27-hydroxycholesterol/cholesterol ratio is increased in low high density lipoprotein-cholesterol healthy subjects.
- Nunes VS, Leança CC, Panzoldo NB, Parra E, Zago V, Cazita PM, Nakandakare ER, de Faria EC, Quintão EC.SourceLipids Laboratory (LIM-10), Endocrinology and Metabolism Division of Hospital das Clinicas, Faculty of Medical Sciences, University of Sao Paulo, Av. Dr. Arnaldo, 455-Room 3305, CEP 01246-00 São Paulo, SP, Brazil. Electronic address: valeriasutti@gmail.com.
- Clinical biochemistry.Clin Biochem.2013 Oct;46(15):1619-21. doi: 10.1016/j.clinbiochem.2013.06.025. Epub 2013 Jul 10.
- Sterol 27-hydroxylase converts cholesterol to 27-hydroxycholesterol (27-OHC) which is widely distributed among tissues and is expressed at high levels in the vascular endothelium and macrophages. There is a continuous flow of this oxysterol from the tissues into the liver, where it is converted to b
- PMID 23850851
- FXR-induced secretion of FGF15/19 inhibits CYP27 expression in cholangiocytes through p38 kinase pathway.
- Jung D, York JP, Wang L, Yang C, Zhang A, Francis HL, Webb P, McKeehan WL, Alpini G, Lesage GD, Moore DD, Xia X.SourceDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
- Pflugers Archiv : European journal of physiology.Pflugers Arch.2013 Sep 26. [Epub ahead of print]
- Cholangiocytes, bile duct lining cells, actively adjust the amount of cholesterol and bile acids in bile through expression of enzymes and channels involved in transportation and metabolism of the cholesterol and bile acids. Herein, we report molecular mechanisms regulating bile acid biosynthesis in
- PMID 24068255
Japanese Journal
- Identification of a Novel Missense Mutation in the Sterol 27-Hydroxylase Gene in Two Japanese Patients with Cerebrotendinous Xanthomatosis
- Nozue Tsuyoshi,Higashikata Toshinori,Inazu Akihiro,Kawashiri Masa-aki,Nohara Atsushi,Kobayashi Junji,Koizumi Junji,Yamagishi Masakazu,Mabuchi Hiroshi
- Internal Medicine 49(12), 1127-1131, 2010
- … Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive sterol storage disease caused by a mutated sterol 27-hydroxylase (CYP27A1) gene. … We analyzed the CYP27A1 gene in two Japanese CTX patients. … The CYP27A1 gene was amplified by PCR and screened by PCR-SSCP. …
- NAID 130000251640
- Hypocholesterolemic Mechanism of Chlorella : Chlorella and Its Indigestible Fraction Enhance Hepatic Cholesterol Catabolism through Up-Regulation of Cholesterol 7α-Hydroxylase in Rats
- Shibata Shinya,Hayakawa Kazuhito,Egashira Yukari [他],SANADA Hiroo
- Bioscience, biotechnology, and biochemistry 71(4), 916-925, 2007-04-23
- … CP increased the hepatic mRNA level and activity of cholesterol 7α-hydroxylase (CYP7A1). … CP did not affect hepatic mRNA levels of sterol 27-hydroxylase, HMGR, low-density lipoprotein (LDL) receptor, scavenger receptor class B1, ATP-binding cassette (ABC) A1, ABCG5, or ABCB11. …
- NAID 10027513400
- Enhanced Susceptibility of LDL to Oxidative Modification in a CTX Patient:-Role of Chenodeoxycholic Acid in Xanthoma Formation-
- Kinoshita Makoto,Kawamura Mitsunobu,Fujita Mineko,Hirota Daisuke,Suda Takaoki,Taki Masanari,Kusano Jyun,Takao Kosuke,Takenaka Hideki,Kubota Shunichiro,Teramoto Tamio
- Journal of Atherosclerosis and Thrombosis 11(3), 167-172, 2004
- … Cerebrotendinous xanthomatosis (CTX) is a rare familial sterol storage disease, causing multiple xanthomas in tendons and the brain. … The underlying biochemical defect is a lack of the hepatic mitochondrial cholesterol 27-hydroxylase involved in the normal biosynthesis of bile acid, resulting in reduced biosynthesis of chenodeoxycholic acid (CDCA). …
- NAID 130004444106
Related Links
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- Sterol 27-Hydroxylase– and ApoAI/Phospholipid–Mediated Efflux of Cholesterol From Cholesterol-Laden Macrophages Evidence for an Inverse Relation Between ... Jan Westman, Bengt Kallin,
Related Pictures
★リンクテーブル★
[★]
- 英
- sterol 27-hydroxylase
- 関
- CYP27A1チトクロムP450、ステロール27-ヒドロキシラーゼ
[★]
- 英
- sterol 27-hydroxylase
- 関
- ステロール27-水酸化酵素
[★]
CYP27A1チトクロムP450
- 関
- sterol 27-hydroxylase
[★]
[★]
コレステロール27-水酸化酵素、コレステロール27-ヒドロキシラーゼ