芳香化酶

芳香化酶、芳香酶（EC 1.14.14.14、英语：Aromatase），也称为雌激素合成酶（英语：estrogen synthetase）或雌激素合酶（英语：estrogen synthase），是一种单加氧酶，负责雌激素生物合成的关键步骤。由人体基因CYP19A1编码，是CYP450酶蛋白质超家族成员，可催化类固醇生成涉及的许多反应。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、脂肪组织、胎盘、血管、皮肤和骨骼，对青春期的第二性征发育有重要作用。

芳香酶催化的睾酮转化到雌二醇的反应。类固醇由四个稠合的环（标记为A到D）组成。芳香酶将标记为A环芳香化

芳香化酶的催化机理：雄烯二酮转化为雌酮的芳香酶催化机理。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]

芳香酶
已知的结构 PDB 直系同源搜索: PDBe RCSB PDBID列表 3EQM、​3S79、​3S7S、​4GL5、​4GL7、​4KQ8
识别号
别名	CYP19A1；, ARO, ARO1, CPV1, CYAR, CYP19, CYPXIX, P-450AROM, cytochrome P450 family 19 subfamily A member 1
外部ID	OMIM：107910 MGI：88587 HomoloGene：30955 GeneCards：CYP19A1
相关疾病
aromatase excess syndrome[1]
为以下药物的标靶
氨鲁米特、​阿那曲唑、​azalanstat、​依西美坦、​法屈唑、​来曲唑、​睾内脂[2]
基因位置（人类） 染色体 15号染色体[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
基因本体 分子功能 • iron ion binding • oxygen binding • 金属离子结合 • 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 细胞组分 • endoplasmic reticulum membrane • 内质网 • 膜 • integral component of membrane 生物学过程 • 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 • 电子传递链 Sources:Amigo / QuickGO
直系同源
物种	人类	小鼠
Entrez	1588	13075
Ensembl	ENSG00000137869	ENSMUSG00000032274
UniProt	P11511	P28649
mRNA​序列	NM_000103 ​NM_001347248 ​NM_001347249 ​NM_001347250 ​NM_001347251 ​NM_001347252 ​NM_001347253 ​NM_001347254 ​NM_001347255 ​NM_001347256 ​NM_031226	NM_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_112503	NP_001335100 ​NP_001335101 ​NP_001335102 ​NP_031836
基因位置​（UCSC）	Chr 15: 51.21 – 51.34 Mb	Chr 9: 54.07 – 54.18 Mb
PubMed​查找	[5]	[6]
维基数据
查看/编辑人类 查看/编辑小鼠

7 sources

催化机理

雄烯二酮 + 3O₂ + 3NADPH + 3H⁺ ${\displaystyle \rightleftharpoons }$ 雌酮 + Formate + 4H₂O + 3NADP⁺

睾酮 + 3O₂ + 3NADPH + 3H⁺ ${\displaystyle \rightleftharpoons }$ 雌二醇 + Formate + 4H₂O + 3NADP⁺

芳香酶催化的睾酮转化到雌二醇的反应。类固醇由四个稠合的环（标记为A到D）组成。芳香酶将标记为A环芳香化

芳香化酶的催化机理：雄烯二酮转化为雌酮的芳香酶催化机理。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]

1 sources

参考文献

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. GRCh38: Ensembl release 89: ENSG00000137869 - Ensembl, May 2017
4. 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. 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.

进一步阅读

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• 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

• "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）.