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维基百科

芳香化酶

九月 25, 2023

芳香化酶、芳香酶（EC 1.14.14.14、英語：Aromatase），也稱為雌激素合成酶（英語：estrogen synthetase）或雌激素合酶（英語：estrogen synthase），是一種單加氧酶，負責雌激素生物合成的關鍵步驟。由人體基因CYP19A1編碼，是CYP450酶蛋白質超家族成員，可催化類固醇生成涉及的許多反應。催化涉及甾体激素合成步骤中从雄激素到雌激素的芳香化（英语：Aromatization）反应。芳香化酶在许多人体组织中出现，如生殖腺（颗粒细胞（英语：granulosa cell））、脑、脂肪組織、胎盤、血管、皮膚和骨骼，对青春期的第二性征发育有重要作用。

芳香酶
已知的結構
PDB直系同源搜索: PDBe RCSB
識別號
别名CYP19A1；, ARO, ARO1, CPV1, CYAR, CYP19, CYPXIX, P-450AROM, cytochrome P450 family 19 subfamily A member 1
外部IDOMIM：107910 MGI：88587 HomoloGene：30955 GeneCards：CYP19A1
相關疾病
aromatase excess syndrome[1]
為以下藥物的標靶
氨鲁米特、​阿那曲唑、​azalanstat、​依西美坦、​法屈唑、​来曲唑、​睾內脂[2]
基因位置（人类）
染色体15號染色體[3]
基因座15q21.2起始51,208,057 bp[3]
终止51,338,601 bp[3]
RNA表达模式
查阅更多表达数据
直系同源
物種人類小鼠
Entrez

1588

13075

Ensembl

ENSG00000137869

ENSMUSG00000032274

UniProt

P11511

P28649

mRNA​序列

NM_007810
​NM_001348171
​NM_001348172
​NM_001348173

蛋白序列

NP_001335100
​NP_001335101
​NP_001335102
​NP_031836

基因位置​（UCSC）Chr 15: 51.21 – 51.34 MbChr 9: 54.07 – 54.18 Mb
PubMed​查找[5][6]
維基數據
檢視/編輯人類檢視/編輯小鼠
芳香酶催化的睾酮轉化到雌二醇的反應。類固醇由四個稠合的環（標記為A到D）組成。芳香酶將標記為A環芳香化
芳香化酶的催化机理：雄烯二酮轉化為雌酮的芳香酶催化機理。雄激素的19-甲基基团经过连续三次羟基化和脱水后，再以甲酸形式消去，同时A环发生芳香化[7]

催化機理 编辑

雄烯二酮 + 3O2 + 3NADPH + 3H+   雌酮 + Formate + 4H2O + 3NADP+
睾酮 + 3O2 + 3NADPH + 3H+   雌二醇 + Formate + 4H2O + 3NADP+
 
芳香酶催化的睾酮轉化到雌二醇的反應。類固醇由四個稠合的環（標記為A到D）組成。芳香酶將標記為A環芳香化
 
芳香化酶的催化机理：雄烯二酮轉化為雌酮的芳香酶催化機理。雄激素的19-甲基基团经过连续三次羟基化和脱水后，再以甲酸形式消去，同时A环发生芳香化[7]

参考文献 编辑

  1. ^ 與芳香酶相關的疾病；在維基數據上查看/編輯參考. 
  2. ^ 對芳香酶起作用的藥物；在維基數據上查看/編輯參考. 
  3. ^ 3.0 3.1 3.2 GRCh38: Ensembl release 89: ENSG00000137869 - Ensembl, May 2017
  4. ^ 4.0 4.1 4.2 GRCm38: Ensembl release 89: ENSMUSG00000032274 - Ensembl, May 2017
  5. ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  6. ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  7. ^ 7.0 7.1 Vaz AD. Chapter 1: Cytochrome activation by cytochromes P450: a role for multiple oxidants in the oxidation of substrates. Fisher M, Lee JK, Obach RE (编). Drug metabolizing enzymes: cytochrome P450 and other enzymes in drug discovery and development. Lausanne, Switzerland: FontisMedia SA. 2003. ISBN 978-0-8247-4293-5. 

進一步閱讀 编辑

  • Attar E, Bulun SE. Aromatase inhibitors: the next generation of therapeutics for endometriosis?. Fertility and Sterility. May 2006, 85 (5): 1307–18. PMID 16647373. doi:10.1016/j.fertnstert.2005.09.064. 
  • Chen S. Aromatase and breast cancer. Frontiers in Bioscience. August 1998, 3 (4): d922–33. PMID 9696881. doi:10.2741/A333. 
  • Strobel HW, Thompson CM, Antonovic L. Cytochromes P450 in brain: function and significance. Current Drug Metabolism. June 2001, 2 (2): 199–214. PMID 11469726. doi:10.2174/1389200013338577. 
  • Simpson ER, Clyne C, Rubin G, Boon WC, Robertson K, Britt K, Speed C, Jones M. Aromatase--a brief overview. Annual Review of Physiology. 2002, 64: 93–127. PMID 11826265. doi:10.1146/annurev.physiol.64.081601.142703. 
  • Bulun SE, Yang S, Fang Z, Gurates B, Tamura M, Zhou J, Sebastian S. Role of aromatase in endometrial disease. The Journal of Steroid Biochemistry and Molecular Biology. December 2001, 79 (1–5): 19–25. PMID 11850203. S2CID 7642211. doi:10.1016/S0960-0760(01)00134-0. 
  • Balthazart J, Baillien M, Ball GF. Phosphorylation processes mediate rapid changes of brain aromatase activity. The Journal of Steroid Biochemistry and Molecular Biology. December 2001, 79 (1–5): 261–77. PMID 11850233. S2CID 34269540. doi:10.1016/S0960-0760(01)00143-1. 
  • Richards JA, Petrel TA, Brueggemeier RW. Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells. The Journal of Steroid Biochemistry and Molecular Biology. February 2002, 80 (2): 203–12. PMID 11897504. S2CID 12728545. doi:10.1016/S0960-0760(01)00187-X. 
  • Balthazart J, Baillien M, Ball GF. Interactions between aromatase (estrogen synthase) and dopamine in the control of male sexual behavior in quail. Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology. May 2002, 132 (1): 37–55. PMID 11997208. doi:10.1016/S1096-4959(01)00531-0. 
  • Meinhardt U, Mullis PE. The aromatase cytochrome P-450 and its clinical impact. Hormone Research. 2002, 57 (5–6): 145–52. PMID 12053085. S2CID 24115725. doi:10.1159/000058374. 
  • Carreau S, Bourguiba S, Lambard S, Galeraud-Denis I, Genissel C, Levallet J. Reproductive system: aromatase and estrogens. Molecular and Cellular Endocrinology. July 2002, 193 (1–2): 137–43. PMID 12161013. S2CID 34446206. doi:10.1016/S0303-7207(02)00107-7. 
  • Meinhardt U, Mullis PE. The essential role of the aromatase/p450arom. Seminars in Reproductive Medicine. August 2002, 20 (3): 277–84. PMID 12428207. doi:10.1055/s-2002-35374. 
  • Carreau S, Bourguiba S, Lambard S, Galeraud-Denis I. [Testicular aromatase]. Journal de la Société de Biologie. 2003, 196 (3): 241–4. PMID 12462076. doi:10.1051/jbio/2002196030241. 
  • Carani C, Fabbi M, Zirilli L, Sgarbi I. [Estrogen resistance and aromatase deficiency in humans]. Journal de la Société de Biologie. 2003, 196 (3): 245–8. PMID 12462077. doi:10.1051/jbio/2002196030245. 
  • Kragie L. Aromatase in primate pregnancy: a review. Endocrine Research. August 2002, 28 (3): 121–8. PMID 12489562. S2CID 8509882. doi:10.1081/ERC-120015041. 
  • Simpson ER. Biology of aromatase in the mammary gland. Journal of Mammary Gland Biology and Neoplasia. July 2000, 5 (3): 251–8. PMID 14973387. S2CID 13296474. doi:10.1023/A:1009590626450. 
  • Bulun SE, Takayama K, Suzuki T, Sasano H, Yilmaz B, Sebastian S. Organization of the human aromatase p450 (CYP19) gene. Seminars in Reproductive Medicine. February 2004, 22 (1): 5–9. PMID 15083376. doi:10.1055/s-2004-823022. 
  • Simpson ER. Aromatase: biologic relevance of tissue-specific expression. Seminars in Reproductive Medicine. February 2004, 22 (1): 11–23. PMID 15083377. doi:10.1055/s-2004-823023. 
  • Bulun SE, Fang Z, Imir G, Gurates B, Tamura M, Yilmaz B, Langoi D, Amin S, Yang S, Deb S. Aromatase and endometriosis. Seminars in Reproductive Medicine. February 2004, 22 (1): 45–50. PMID 15083380. doi:10.1055/s-2004-823026. 
  • Shozu M, Murakami K, Inoue M. Aromatase and leiomyoma of the uterus. Seminars in Reproductive Medicine. February 2004, 22 (1): 51–60. PMID 15083381. doi:10.1055/s-2004-823027. 
  • Chen S, Ye J, Kijima I, Kinoshita Y, Zhou D. Positive and negative transcriptional regulation of aromatase expression in human breast cancer tissue. The Journal of Steroid Biochemistry and Molecular Biology. May 2005, 95 (1–5): 17–23. PMID 15955695. S2CID 22138523. doi:10.1016/j.jsbmb.2005.04.002. 
  • Lambard S, Silandre D, Delalande C, Denis-Galeraud I, Bourguiba S, Carreau S. Aromatase in testis: expression and role in male reproduction. The Journal of Steroid Biochemistry and Molecular Biology. May 2005, 95 (1–5): 63–9. PMID 16019206. S2CID 40087589. doi:10.1016/j.jsbmb.2005.04.020. 
  • Bulun SE, Imir G, Utsunomiya H, Thung S, Gurates B, Tamura M, Lin Z. Aromatase in endometriosis and uterine leiomyomata. The Journal of Steroid Biochemistry and Molecular Biology. May 2005, 95 (1–5): 57–62. PMID 16024248. S2CID 37228186. doi:10.1016/j.jsbmb.2005.04.012. 
  • Lambard S, Carreau S. Aromatase and oestrogens in human male germ cells. International Journal of Andrology. October 2005, 28 (5): 254–9. PMID 16128984. doi:10.1111/j.1365-2605.2005.00546.x  . 
  • Ellem SJ, Risbridger GP. Aromatase and prostate cancer. Minerva Endocrinologica. March 2006, 31 (1): 1–12. PMID 16498360. 
  • Brueggemeier RW, Díaz-Cruz ES. Relationship between aromatase and cyclooxygenases in breast cancer: potential for new therapeutic approaches. Minerva Endocrinologica. March 2006, 31 (1): 13–26. PMID 16498361. 
  • Jongen VH, Hollema H, Van Der Zee AG, Heineman MJ. Aromatase in the context of breast and endometrial cancer. A review. Minerva Endocrinologica. March 2006, 31 (1): 47–60. PMID 16498363. 
  • Hiltunen M, Iivonen S, Soininen H. Aromatase enzyme and Alzheimer's disease. Minerva Endocrinologica. March 2006, 31 (1): 61–73. PMID 16498364. 


外部链接 编辑

  • "U.S. study of gay sheep may shed light on sexuality", via WikiNews, 15 August 2005.
  • Human CYP19A1 genome location and CYP19A1 gene details page in the UCSC Genome Browser（英语：UCSC Genome Browser）.

九月 25, 2023
芳香化酶, 芳香酶, 英語, aromatase, 也稱為雌激素合成酶, 英語, estrogen, synthetase, 或雌激素合酶, 英語, estrogen, synthase, 是一種單加氧酶, 負責雌激素生物合成的關鍵步驟, 由人體基因cyp19a1編碼, 是cyp450酶蛋白質超家族成員, 可催化類固醇生成涉及的許多反應, 催化涉及甾体激素合成步骤中从雄激素到雌激素的芳香化, 英语, aromatization, 反应, 在许多人体组织中出现, 如生殖腺, 颗粒细胞, 英语, granulosa, . 芳香化酶 芳香酶 EC 1 14 14 14 英語 Aromatase 也稱為雌激素合成酶 英語 estrogen synthetase 或雌激素合酶 英語 estrogen synthase 是一種單加氧酶 負責雌激素生物合成的關鍵步驟 由人體基因CYP19A1編碼 是CYP450酶蛋白質超家族成員 可催化類固醇生成涉及的許多反應 催化涉及甾体激素合成步骤中从雄激素到雌激素的芳香化 英语 Aromatization 反应 芳香化酶在许多人体组织中出现 如生殖腺 颗粒细胞 英语 granulosa cell 脑 脂肪組織 胎盤 血管 皮膚和骨骼 对青春期的第二性征发育有重要作用 芳香酶已知的結構PDB直系同源搜索 PDBe RCSBPDBID列表3EQM 3S79 3S7S 4GL5 4GL7 4KQ8識別號别名CYP19A1 ARO ARO1 CPV1 CYAR CYP19 CYPXIX P 450AROM cytochrome P450 family 19 subfamily A member 1外部IDOMIM 107910 MGI 88587 HomoloGene 30955 GeneCards CYP19A1相關疾病aromatase excess syndrome 1 為以下藥物的標靶氨鲁米特 阿那曲唑 azalanstat 依西美坦 法屈唑 来曲唑 睾內脂 2 基因位置 人类 染色体15號染色體 3 基因座15q21 2起始51 208 057 bp 3 终止51 338 601 bp 3 基因位置 小鼠 染色体小鼠9号染色体 4 基因座9 A5 3 9 29 49 cM起始54 073 221 bp 4 终止54 175 394 bp 4 RNA表达模式查阅更多表达数据基因本體分子功能 iron ion binding oxygen binding 金屬離子結合 monooxygenase activity heme binding oxidoreductase activity acting on paired donors with incorporation or reduction of molecular oxygen electron transfer activity oxidoreductase activity aromatase activity oxidoreductase activity acting on paired donors with incorporation or reduction of molecular oxygen reduced flavin or flavoprotein as one donor and incorporation of one atom of oxygen steroid hydroxylase activity細胞組分 endoplasmic reticulum membrane 内质网 膜 integral component of membrane生物學過程 estrogen biosynthetic process androgen metabolic process negative regulation of chronic inflammatory response prostate gland growth sterol metabolic process negative regulation of macrophage chemotaxis steroid biosynthetic process female gonad development female genitalia development 乳腺发育 uterus development testosterone biosynthetic process androgen catabolic process positive regulation of estradiol secretion 電子傳遞鏈Sources Amigo QuickGO直系同源物種人類小鼠Entrez158813075EnsemblENSG00000137869ENSMUSG00000032274UniProtP11511P28649mRNA 序列NM 000103 NM 001347248 NM 001347249 NM 001347250 NM 001347251 NM 001347252 NM 001347253 NM 001347254 NM 001347255 NM 001347256 NM 031226NM 007810 NM 001348171 NM 001348172 NM 001348173蛋白序列NP 000094 NP 001334177 NP 001334178 NP 001334179 NP 001334180 NP 001334181 NP 001334182 NP 001334183 NP 001334184 NP 001334185 NP 112503NP 001335100 NP 001335101 NP 001335102 NP 031836基因位置 UCSC Chr 15 51 21 51 34 MbChr 9 54 07 54 18 MbPubMed 查找 5 6 維基數據檢視 編輯人類檢視 編輯小鼠 芳香酶催化的睾酮轉化到雌二醇的反應 類固醇由四個稠合的環 標記為A到D 組成 芳香酶將標記為A環芳香化芳香化酶的催化机理 雄烯二酮轉化為雌酮的芳香酶催化機理 雄激素的19 甲基基团经过连续三次羟基化和脱水后 再以甲酸形式消去 同时A环发生芳香化 7 目录 1 催化機理 2 参考文献 3 進一步閱讀 4 外部链接催化機理 编辑雄烯二酮 3O2 3NADPH 3H displaystyle rightleftharpoons nbsp 雌酮 Formate 4H2O 3NADP 睾酮 3O2 3NADPH 3H displaystyle rightleftharpoons nbsp 雌二醇 Formate 4H2O 3NADP nbsp 芳香酶催化的睾酮轉化到雌二醇的反應 類固醇由四個稠合的環 標記為A到D 組成 芳香酶將標記為A環芳香化 nbsp 芳香化酶的催化机理 雄烯二酮轉化為雌酮的芳香酶催化機理 雄激素的19 甲基基团经过连续三次羟基化和脱水后 再以甲酸形式消去 同时A环发生芳香化 7 参考文献 编辑 與芳香酶相關的疾病 在維基數據上查看 編輯參考 對芳香酶起作用的藥物 在維基數據上查看 編輯參考 3 0 3 1 3 2 GRCh38 Ensembl release 89 ENSG00000137869 Ensembl May 2017 4 0 4 1 4 2 GRCm38 Ensembl release 89 ENSMUSG00000032274 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine 7 0 7 1 Vaz AD Chapter 1 Cytochrome activation by cytochromes P450 a role for multiple oxidants in the oxidation of substrates Fisher M Lee JK Obach RE 编 Drug metabolizing enzymes cytochrome P450 and other enzymes in drug discovery and development Lausanne Switzerland FontisMedia SA 2003 ISBN 978 0 8247 4293 5 進一步閱讀 编辑Attar E Bulun SE Aromatase inhibitors the next generation of therapeutics for endometriosis Fertility and Sterility May 2006 85 5 1307 18 PMID 16647373 doi 10 1016 j fertnstert 2005 09 064 Chen S Aromatase and breast cancer Frontiers in Bioscience August 1998 3 4 d922 33 PMID 9696881 doi 10 2741 A333 Strobel HW Thompson CM Antonovic L Cytochromes P450 in brain function and significance Current Drug Metabolism June 2001 2 2 199 214 PMID 11469726 doi 10 2174 1389200013338577 Simpson ER Clyne C Rubin G Boon WC Robertson K Britt K Speed C Jones M Aromatase a brief overview Annual Review of Physiology 2002 64 93 127 PMID 11826265 doi 10 1146 annurev physiol 64 081601 142703 Bulun SE Yang S Fang Z Gurates B Tamura M Zhou J Sebastian S Role of aromatase in endometrial disease The Journal of Steroid Biochemistry and Molecular Biology December 2001 79 1 5 19 25 PMID 11850203 S2CID 7642211 doi 10 1016 S0960 0760 01 00134 0 Balthazart J Baillien M Ball GF Phosphorylation processes mediate rapid changes of brain aromatase activity The Journal of Steroid Biochemistry and Molecular Biology December 2001 79 1 5 261 77 PMID 11850233 S2CID 34269540 doi 10 1016 S0960 0760 01 00143 1 Richards JA Petrel TA Brueggemeier RW Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells The Journal of Steroid Biochemistry and Molecular Biology February 2002 80 2 203 12 PMID 11897504 S2CID 12728545 doi 10 1016 S0960 0760 01 00187 X Balthazart J Baillien M Ball GF Interactions between aromatase estrogen synthase and dopamine in the control of male sexual behavior in quail Comparative Biochemistry and Physiology Part B Biochemistry amp Molecular Biology May 2002 132 1 37 55 PMID 11997208 doi 10 1016 S1096 4959 01 00531 0 Meinhardt U Mullis PE The aromatase cytochrome P 450 and its clinical impact Hormone Research 2002 57 5 6 145 52 PMID 12053085 S2CID 24115725 doi 10 1159 000058374 Carreau S Bourguiba S Lambard S Galeraud Denis I Genissel C Levallet J Reproductive system aromatase and estrogens Molecular and Cellular Endocrinology July 2002 193 1 2 137 43 PMID 12161013 S2CID 34446206 doi 10 1016 S0303 7207 02 00107 7 Meinhardt U Mullis PE The essential role of the aromatase p450arom Seminars in Reproductive Medicine August 2002 20 3 277 84 PMID 12428207 doi 10 1055 s 2002 35374 Carreau S Bourguiba S Lambard S Galeraud Denis I Testicular aromatase Journal de la Societe de Biologie 2003 196 3 241 4 PMID 12462076 doi 10 1051 jbio 2002196030241 Carani C Fabbi M Zirilli L Sgarbi I Estrogen resistance and aromatase deficiency in humans Journal de la Societe de Biologie 2003 196 3 245 8 PMID 12462077 doi 10 1051 jbio 2002196030245 Kragie L Aromatase in primate pregnancy a review Endocrine Research August 2002 28 3 121 8 PMID 12489562 S2CID 8509882 doi 10 1081 ERC 120015041 Simpson ER Biology of aromatase in the mammary gland Journal of Mammary Gland Biology and Neoplasia July 2000 5 3 251 8 PMID 14973387 S2CID 13296474 doi 10 1023 A 1009590626450 Bulun SE Takayama K Suzuki T Sasano H Yilmaz B Sebastian S Organization of the human aromatase p450 CYP19 gene Seminars in Reproductive Medicine February 2004 22 1 5 9 PMID 15083376 doi 10 1055 s 2004 823022 Simpson ER Aromatase biologic relevance of tissue specific expression Seminars in Reproductive Medicine February 2004 22 1 11 23 PMID 15083377 doi 10 1055 s 2004 823023 Bulun SE Fang Z Imir G Gurates B Tamura M Yilmaz B Langoi D Amin S Yang S Deb S Aromatase and endometriosis Seminars in Reproductive Medicine February 2004 22 1 45 50 PMID 15083380 doi 10 1055 s 2004 823026 Shozu M Murakami K Inoue M Aromatase and leiomyoma of the uterus Seminars in Reproductive Medicine February 2004 22 1 51 60 PMID 15083381 doi 10 1055 s 2004 823027 Chen S Ye J Kijima I Kinoshita Y Zhou D Positive and negative transcriptional regulation of aromatase expression in human breast cancer tissue The Journal of Steroid Biochemistry and Molecular Biology May 2005 95 1 5 17 23 PMID 15955695 S2CID 22138523 doi 10 1016 j jsbmb 2005 04 002 Lambard S Silandre D Delalande C Denis Galeraud I Bourguiba S Carreau S Aromatase in testis expression and role in male reproduction The Journal of Steroid Biochemistry and Molecular Biology May 2005 95 1 5 63 9 PMID 16019206 S2CID 40087589 doi 10 1016 j jsbmb 2005 04 020 Bulun SE Imir G Utsunomiya H Thung S Gurates B Tamura M Lin Z Aromatase in endometriosis and uterine leiomyomata The Journal of Steroid Biochemistry and Molecular Biology May 2005 95 1 5 57 62 PMID 16024248 S2CID 37228186 doi 10 1016 j jsbmb 2005 04 012 Lambard S Carreau S Aromatase and oestrogens in human male germ cells International Journal of Andrology October 2005 28 5 254 9 PMID 16128984 doi 10 1111 j 1365 2605 2005 00546 x nbsp Ellem SJ Risbridger GP Aromatase and prostate cancer Minerva Endocrinologica March 2006 31 1 1 12 PMID 16498360 Brueggemeier RW Diaz Cruz ES Relationship between aromatase and cyclooxygenases in breast cancer potential for new therapeutic approaches Minerva Endocrinologica March 2006 31 1 13 26 PMID 16498361 Jongen VH Hollema H Van Der Zee AG Heineman MJ Aromatase in the context of breast and endometrial cancer A review Minerva Endocrinologica March 2006 31 1 47 60 PMID 16498363 Hiltunen M Iivonen S Soininen H Aromatase enzyme and Alzheimer s disease Minerva Endocrinologica March 2006 31 1 61 73 PMID 16498364 外部链接 编辑 U S study of gay sheep may shed light on sexuality via WikiNews 15 August 2005 Human CYP19A1 genome location and CYP19A1 gene details page in the UCSC Genome Browser 英语 UCSC Genome Browser 取自 https zh wikipedia org w index php title 芳香化酶 amp oldid 78974261, 维基百科，wiki，书籍，书籍，图书馆，

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