芳香化酶

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。催化涉及甾體激素合成步驟中從雄激素到雌激素的芳香化（英語：Aromatization）反應。芳香化酶在許多人體組織中出現，如生殖腺（顆粒細胞（英語：granulosa cell））、腦、脂肪組織、胎盤、血管、皮膚和骨骼，對青春期的第二性徵發育有重要作用。

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

芳香化酶的催化機理：雄烯二酮轉化為雌酮的芳香酶催化機理。雄激素的19-甲基基團經過連續三次羥基化和脫水後，再以甲酸形式消去，同時A環發生芳香化^[7]

芳香酶
已知的結構 PDB 直系同源搜索: PDBe RCSB PDBID列表 3EQM、​3S79、​3S7S、​4GL5、​4GL7、​4KQ8
識別號
別名	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
相關疾病
aromatase excess syndrome[1]
為以下藥物的標靶
氨魯米特、​阿那曲唑、​azalanstat、​依西美坦、​法屈唑、​來曲唑、​睾內脂[2]
基因位置（人類） 染色體 15號染色體[3] 基因座 15q21.2 起始 51,208,057 bp[3] 終止 51,338,601 bp[3]
基因位置（小鼠） 染色體 小鼠9號染色體[4] 基因座 9 A5.3|9 29.49 cM 起始 54,073,221 bp[4] 終止 54,175,394 bp[4]
RNA表達模式
查閱更多表達數據
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 • 內質網 • 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 • 乳腺發育 • 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
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]
維基數據
檢視/編輯人類 檢視/編輯小鼠

催化機理

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

芳香化酶的催化機理：雄烯二酮轉化為雌酮的芳香酶催化機理。雄激素的19-甲基基團經過連續三次羥基化和脫水後，再以甲酸形式消去，同時A環發生芳香化^[7]

參考文獻

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 (編). 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

• 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.

外部連結

• "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（英語：UCSC Genome Browser）.