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CYP27A1 |
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Available structures |
PDB |
Ortholog search: PDBe RCSB |
List of PDB id codes |
1MFX
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Identifiers |
Aliases |
CYP27A1, CP27, CTX, CYP27, cytochrome P450 family 27 subfamily A member 1 |
External IDs |
OMIM: 606530 MGI: 88594 HomoloGene: 36040 GeneCards: CYP27A1 |
Gene ontology |
Molecular function |
• monooxygenase activity
• iron ion binding
• steroid hydroxylase activity
• oxidoreductase activity
• heme binding
• oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
• metal ion binding
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Cellular component |
• mitochondrial inner membrane
• mitochondrial matrix
• membrane
• mitochondrion
• mitochondrial membrane
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Biological process |
• sterol metabolic process
• bile acid biosynthetic process
• oxidation-reduction 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 |
Entrez |
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Ensembl |
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UniProt |
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RefSeq (mRNA) |
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RefSeq (protein) |
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Location (UCSC) |
Chr 2: 218.78 – 218.82 Mb |
Chr 1: 74.71 – 74.74 Mb |
PubMed search |
[1] |
[2] |
Wikidata |
View/Edit Human |
View/Edit Mouse |
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
CYP27A1 participates in the degradation of cholesterol to bile acids in both the classic and acidic pathways.[3] 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.[4]
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.[5]
Clinical significance
Mutations in CYP27A1 are associated with cerebrotendineous xanthomatosis, a rare lipid storage disease.
Inhibitors of CYP27A1 may be effective as adjuvants in the treatment of ER-positive breast cancer due to inhibition of the production of 27-hydroxycholesterol (which has estrogenic actions and stimulates the growth of ER-positive breast cancer cells).[6] Some marketed drugs that have been identified as CYP27A1 inhibitors include anastrozole, fadrozole, bicalutamide, dexmedetomidine, ravuconazole, and posaconazole.[6]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
[[File:
|{{{bSize}}}px|alt=Vitamin D Synthesis Pathway edit]]
File:VitaminDSynthesis WP1531.png
Vitamin D Synthesis Pathway edit
- ^ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".
References
- ^ "Human PubMed Reference:".
- ^ "Mouse PubMed Reference:".
- ^ Chiang JY (Feb 1998). "Regulation of bile acid synthesis". Frontiers in Bioscience. 3: d176–93. PMID 9450986.
- ^ Sakaki T, Kagawa N, Yamamoto K, Inouye K (Jan 2005). "Metabolism of vitamin D3 by cytochromes P450". Frontiers in Bioscience. 10: 119–34. doi:10.2741/1514. PMID 15574355.
- ^ Taylor JM, Borthwick F, Bartholomew C, Graham A (Jun 2010). "Overexpression of steroidogenic acute regulatory protein increases macrophage cholesterol efflux to apolipoprotein AI". Cardiovascular Research. 86 (3): 526–34. doi:10.1093/cvr/cvq015. PMID 20083572.
- ^ a b Mast N, Lin JB, Pikuleva IA (Sep 2015). "Marketed Drugs Can Inhibit Cytochrome P450 27A1, a Potential New Target for Breast Cancer Adjuvant Therapy". Molecular Pharmacology. 88 (3): 428–36. doi:10.1124/mol.115.099598. PMID 26082378.
Further reading
- Cali JJ, Russell DW (Apr 1991). "Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis". The Journal of Biological Chemistry. 266 (12): 7774–8. PMID 1708392.
- Cali JJ, Hsieh CL, Francke U, Russell DW (Apr 1991). "Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis". The Journal of Biological Chemistry. 266 (12): 7779–83. PMID 2019602.
- Guo YD, Strugnell S, Back DW, Jones G (Sep 1993). "Transfected human liver cytochrome P-450 hydroxylates vitamin D analogs at different side-chain positions". Proceedings of the National Academy of Sciences of the United States of America. 90 (18): 8668–72. doi:10.1073/pnas.90.18.8668. PMC 47419. PMID 7690968.
- Kim KS, Kubota S, Kuriyama M, Fujiyama J, Björkhem I, Eggertsen G, Seyama Y (Jun 1994). "Identification of new mutations in sterol 27-hydroxylase gene in Japanese patients with cerebrotendinous xanthomatosis (CTX)". Journal of Lipid Research. 35 (6): 1031–9. PMID 7915755.
- Maruyama K, Sugano S (Jan 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, Levitzki R, Schwartz SP, Dann EJ, Berkman N, Cali JJ, Klapholz L, Berginer VM (Jun 1993). "Frameshift and splice-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis in Jews or Moroccan origin". The Journal of Clinical Investigation. 91 (6): 2488–96. doi:10.1172/JCI116484. PMC 443309. PMID 8514861.
- Chen W, Kubota S, Kim KS, Cheng J, Kuriyama M, Eggertsen G, Björkhem I, Seyama Y (May 1997). "Novel homozygous and compound heterozygous mutations of sterol 27-hydroxylase gene (CYP27) cause cerebrotendinous xanthomatosis in three Japanese patients from two unrelated families". Journal of Lipid Research. 38 (5): 870–9. PMID 9186905.
- Reiss AB, Martin KO, Rojer DE, Iyer S, Grossi EA, Galloway AC, Javitt NB (Jun 1997). "Sterol 27-hydroxylase: expression in human arterial endothelium". Journal of Lipid Research. 38 (6): 1254–60. PMID 9215552.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 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, Ishihara T, Seyama Y (Oct 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, Nakajima K, Fushiki S (Nov 1999). "Mutation of the sterol 27-hydroxylase gene (CYP27) results in truncation of mRNA expressed in leucocytes in a Japanese family with cerebrotendinous xanthomatosis". Journal of Neurology, Neurosurgery, and Psychiatry. 67 (5): 675–7. doi:10.1136/jnnp.67.5.675. PMC 1736608. PMID 10519880.
- Gascon-Barré M, Demers C, Ghrab O, Theodoropoulos C, Lapointe R, Jones G, Valiquette L, Ménard D (Jan 2001). "Expression of CYP27A, a gene encoding a vitamin D-25 hydroxylase in human liver and kidney". Clinical Endocrinology. 54 (1): 107–15. doi:10.1046/j.1365-2265.2001.01160.x. PMID 11167933.
- Johnston TP, Nguyen LB, Chu WA, Shefer S (Oct 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, Shiga K, Ishibashi S, Fushiki S (Jan 2002). "A Japanese patient with cerebrotendinous xanthomatosis has different mutations within two functional domains of CYP27". Clinical Genetics. 61 (1): 77–8. doi:10.1034/j.1399-0004.2002.610116.x. PMID 11903362.
- Lamon-Fava S, Schaefer EJ, Garuti R, Salen G, Calandra S (Mar 2002). "Two novel mutations in the sterol 27-hydroxylase gene causing cerebrotendinous xanthomatosis". Clinical Genetics. 61 (3): 185–91. doi:10.1034/j.1399-0004.2002.610303.x. PMID 12000359.
- Björkhem I, Araya Z, Rudling M, Angelin B, Einarsson C, Wikvall K (Jul 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". The Journal of Biological Chemistry. 277 (30): 26804–7. doi:10.1074/jbc.M202343200. PMID 12011083.
- von Bahr S, Movin T, Papadogiannakis N, Pikuleva I, Rönnow P, Diczfalusy U, Björkhem I (Jul 2002). "Mechanism of accumulation of cholesterol and cholestanol in tendons and the role of sterol 27-hydroxylase (CYP27A1)". Arteriosclerosis, Thrombosis, and Vascular Biology. 22 (7): 1129–35. doi:10.1161/01.ATV.0000022600.61391.A5. PMID 12117727.
- Meir K, Kitsberg D, Alkalay I, Szafer F, Rosen H, Shpitzen S, Avi LB, Staels B, Fievet C, Meiner V, Björkhem I, Leitersdorf E (Sep 2002). "Human sterol 27-hydroxylase (CYP27) overexpressor transgenic mouse model. Evidence against 27-hydroxycholesterol as a critical regulator of cholesterol homeostasis". The Journal of Biological Chemistry. 277 (37): 34036–41. doi:10.1074/jbc.M201122200. PMID 12119285.
- Lee MJ, Huang YC, Sweeney MG, Wood NW, Reilly MM, Yip PK (Sep 2002). "Mutation of the sterol 27-hydroxylase gene ( CYP27A1) in a Taiwanese family with cerebrotendinous xanthomatosis". Journal of Neurology. 249 (9): 1311–2. doi:10.1007/s00415-002-0762-9. PMID 12242561.
External links
- 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
- Cholesterol total synthesis
- Reverse cholesterol transport
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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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Metabolism of vitamins, coenzymes, and cofactors
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Fat soluble vitamins |
Vitamin A |
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Vitamin E |
- Alpha-tocopherol transfer protein
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Vitamin D |
- 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 |
- Vitamin K epoxide reductase
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Water soluble vitamins |
Thiamine (B1) |
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Niacin (B3) |
- Indoleamine 2,3-dioxygenase
- Formamidase
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Pantothenic acid (B5) |
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Folic acid (B9) |
- 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 |
- GTP cyclohydrolase I
- 6-pyruvoyltetrahydropterin synthase
- Sepiapterin reductase
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Molybdenum cofactor |
- MOCS1
- MOCS2
- MOCS3
- Gephyrin
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Enzymes
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Activity |
- Active site
- Binding site
- Catalytic triad
- Oxyanion hole
- Enzyme promiscuity
- Catalytically perfect enzyme
- Coenzyme
- Cofactor
- Enzyme catalysis
- Enzyme kinetics
- Lineweaver–Burk plot
- Michaelis–Menten kinetics
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Regulation |
- Allosteric regulation
- Cooperativity
- Enzyme inhibitor
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Classification |
- EC number
- Enzyme superfamily
- Enzyme family
- List of enzymes
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Types |
- EC1 Oxidoreductases (list)
- EC2 Transferases (list)
- EC3 Hydrolases (list)
- EC4 Lyases (list)
- EC5 Isomerases (list)
- EC6 Ligases (list)
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UpToDate Contents
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- 1. 脳腱黄色腫症 cerebrotendinous xanthomatosis
English Journal
- High-Throughput and Reliable Isotope Label-free Approach for Profiling 24 Metabolic Enzymes in FVB Mice and Sex Differences.
- Chen J1, Zhu L1, Li X1, Zheng H1, Yan T1, Xie C1, Zeng S1, Yu J1, Jiang H1, Lu L1, Qi X1, Wang Y1, Hu M1, Liu Z2.
- Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2017 Jun;45(6):624-634. doi: 10.1124/dmd.116.074682. Epub 2017 Mar 29.
- PMID 28356314
- Common genetic etiology between "multiple sclerosis-like" single-gene disorders and familial multiple sclerosis.
- Traboulsee AL1, Sadovnick AD1,2, Encarnacion M2, Bernales CQ2, Yee IM2, Criscuoli MG2, Vilariño-Güell C3.
- Human genetics.Hum Genet.2017 Jun;136(6):705-714. doi: 10.1007/s00439-017-1784-9. Epub 2017 Mar 23.
- PMID 28337550
- Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia.
- Mistry HD1,2, Kurlak LO2, Mansour YT3, Zurkinden L4, Mohaupt MG4, Escher G4.
- Journal of lipid research.J Lipid Res.2017 Jun;58(6):1186-1195. doi: 10.1194/jlr.M071985. Epub 2017 Apr 10.
- PMID 28396342
Japanese Journal
- Hepatic Cholesterol Metabolism Following a Chronic Ingestion of Cesium-137 Starting at Fetal Stage in Rats
- Racine Radjini,Grandcolas Line,Blanchardon Eric [他],GOURMELON Patrick,VEYSSIERE Georges,SOUIDI Maamar
- Journal of radiation research 51(1), 37-45, 2010-01-16
- … In addition, the enzymatic activity of CYP27A1, which catabolizes cholesterol, was increased. …
- NAID 10025914063
- 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
- 腎癌におけるビタミンD活性化関連遺伝子CYP27A1・CYP27B1・CYP24の発現と活性型ビタミンD添加による発現の変化
Related Links
- 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 ...
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★リンクテーブル★
[★]
- 英
- cytochrome P-450 CYP27A1
- 関
- ステロール27-水酸化酵素
[★]
CYP27A1チトクロムP450
- 関
- sterol 27-hydroxylase