Metabolic Modeling Tutorial
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
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MetaCyc Enzyme: aromatase

Gene: CYP19A1 Accession Number: HS06413 (MetaCyc)

Synonyms: ARO1, CYAR, CYP19, cytochrome P450 19A1, CYPXIX, estrogen synthetase, P-450AROM

Species: Homo sapiens

Summary:
CYP19A1 encodes aromatase, a member of the cytochrome P450 superfamily of enzymes. The protein localizes to the endoplasmic reticulum and catalyzes the last steps of estrogen biosynthesis, three successive hydroxylations of the A ring of the androgens androst-4-ene-3,17-dione or testosterone, resulting in aromatization to form the asterogens estrone and 17β-estradiol, respectively.

Mutations in this gene can result in either increased or decreased aromatase activity; the associated phenotypes suggest that estrogen functions both as a sex steroid hormone and in growth or differentiation.

Citations: [Herrmann02, Carani02, Carreau02, Zhou02b, Gurates02, Yang02e, Berstein02, Clyne02, Kado02, Mukherjee02, Ellis01a, Richards02a, Conley01, Balthazart01, Mor01, Hinshelwood01, Yanase01, Kamat01, Parish01, Yue01, Harada01, Brueggemeier01, Murakami01, Shozu01, Brodie01, Chen01c, Bulun01, Toda93, Simpson87, Chen88, Harada88, Corbin88, Means89, Toda89, Toda90, Means91, Harada92]

Locations: membrane

Map Position: [44,547,646 <- 44,676,082]

Unification Links: ArrayExpress:P11511 , Ensembl:ENSG00000137869 , Entrez-gene:1588 , Entrez-Nucleotide:BC022896 , Entrez-Nucleotide:BC035959 , Entrez-Nucleotide:D14473 , Entrez-Nucleotide:J04127 , Entrez-Nucleotide:M18856 , Entrez-Nucleotide:M22246 , Entrez-Nucleotide:M28420 , Entrez-Nucleotide:M30804 , Entrez-Nucleotide:S85356 , Entrez-Nucleotide:X13589 , Entrez-Nucleotide:Y07508 , Entrez:AAA35556 , Entrez:AAA35557 , Entrez:AAA35728 , Entrez:AAA52132 , Entrez:AAA52141 , Entrez:AAB21520 , Entrez:AAH22896 , Entrez:AAH35959 , Entrez:CAA31929 , Entrez:CAA68807 , Mint:MINT-4054553 , OMIM:107910 , PhosphoSite:P11511 , PhylomeDB:P11511 , Pride:P11511 , Protein Model Portal:P11511 , RefSeq:NM_000103 , RefSeq:NM_031226 , RefSeq:NP_000094 , RefSeq:NP_112503 , SMR:P11511 , String:9606.ENSP00000260433 , UCSC Human Genome:NM_031226 , UniGene:79946 , UniProt:P11511

Relationship Links: InterPro:IN-FAMILY:IPR001128 , InterPro:IN-FAMILY:IPR002401 , InterPro:IN-FAMILY:IPR017972 , PDB:Structure:1TQA , PDB:Structure:3EQM , PDB:Structure:3S79 , PDB:Structure:3S7S , PDB:Structure:4GL5 , PDB:Structure:4GL7 , PDB:Structure:4KQ8 , Pfam:IN-FAMILY:PF00067 , Prints:IN-FAMILY:PR00385 , Prints:IN-FAMILY:PR00463 , Prosite:IN-FAMILY:PS00086

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0006694 - steroid biosynthetic process
Molecular Function: GO:0004497 - monooxygenase activity
GO:0016712 - 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
Cellular Component: GO:0016020 - membrane


Enzymatic reaction of: 19-oxotestosterone 2-βhydroxylase (aromatase)

19-oxo-testosterone + a reduced flavoprotein + oxygen <=> 17β-estradiol + formate + an oxidized flavoprotein + H2O + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , estradiol biosynthesis II


Enzymatic reaction of: 19-hydroxytestosterone 19-dehydrogenase (aromatase)

19-hydroxytestosterone + a reduced flavoprotein + oxygen <=> 19-oxo-testosterone + an oxidized flavoprotein + 2 H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , estradiol biosynthesis II


Enzymatic reaction of: testosterone 19-hydroxylase (aromatase)

testosterone + a reduced flavoprotein + oxygen <=> 19-hydroxytestosterone + an oxidized flavoprotein + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , estradiol biosynthesis II


Enzymatic reaction of: 19-oxoandrostenedione 2-βhydroxylase (aromatase)

19-oxoandrostenedione + a reduced flavoprotein + oxygen <=> estrone + formate + an oxidized flavoprotein + H2O + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , estradiol biosynthesis I (via estrone)


Enzymatic reaction of: 19-hydroxyandrostenedione 19-hydrogenase (aromatase)

19-hydroxyandrostenedione + a reduced flavoprotein + oxygen <=> 19-oxoandrostenedione + an oxidized flavoprotein + 2 H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , estradiol biosynthesis I (via estrone)


Enzymatic reaction of: androstenedione 19-hydroxylase (aromatase)

androst-4-ene-3,17-dione + a reduced flavoprotein + oxygen <=> 19-hydroxyandrostenedione + an oxidized flavoprotein + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , estradiol biosynthesis I (via estrone)


References

Balthazart01: Balthazart J, Baillien M, Ball GF (2001). "Phosphorylation processes mediate rapid changes of brain aromatase activity." J Steroid Biochem Mol Biol 79(1-5);261-77. PMID: 11850233

Berstein02: Berstein LM, Larionov AA, Poroshina TE, Zimarina TS, Leenman EE (2002). "Aromatase (CYP19) expression in tumor-infiltrating lymphocytes and blood mononuclears." J Cancer Res Clin Oncol 128(3);173-6. PMID: 11935306

Brodie01: Brodie AM, Lu Q, Long BJ, Fulton A, Chen T, Macpherson N, DeJong PC, Blankenstein MA, Nortier JW, Slee PH, van de Ven J, van Gorp JM, Elbers JR, Schipper ME, Blijham GH, Thijssen JH (2001). "Aromatase and COX-2 expression in human breast cancers." J Steroid Biochem Mol Biol 79(1-5);41-7. PMID: 11850206

Brueggemeier01: Brueggemeier RW, Richards JA, Joomprabutra S, Bhat AS, Whetstone JL (2001). "Molecular pharmacology of aromatase and its regulation by endogenous and exogenous agents." J Steroid Biochem Mol Biol 79(1-5);75-84. PMID: 11850210

Bulun01: Bulun SE, Yang S, Fang Z, Gurates B, Tamura M, Zhou J, Sebastian S (2001). "Role of aromatase in endometrial disease." J Steroid Biochem Mol Biol 79(1-5);19-25. PMID: 11850203

Carani02: Carani C, Fabbi M, Zirilli L, Sgarbi I (2002). "[Estrogen resistance and aromatase deficiency in humans]." J Soc Biol 196(3);245-8. PMID: 12462077

Carreau02: Carreau S, Bourguiba S, Lambard S, Galeraud-Denis I (2002). "[Testicular aromatase]." J Soc Biol 196(3);241-4. PMID: 12462076

Chen01c: Chen S, Zhou D, Yang C, Okubo T, Kinoshita Y, Yu B, Kao YC, Itoh T (2001). "Modulation of aromatase expression in human breast tissue." J Steroid Biochem Mol Biol 79(1-5);35-40. PMID: 11850205

Chen88: Chen SA, Besman MJ, Sparkes RS, Zollman S, Klisak I, Mohandas T, Hall PF, Shively JE (1988). "Human aromatase: cDNA cloning, Southern blot analysis, and assignment of the gene to chromosome 15." DNA 7(1);27-38. PMID: 3390233

Clyne02: Clyne CD, Speed CJ, Zhou J, Simpson ER (2002). "Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes." J Biol Chem 277(23);20591-7. PMID: 11927588

Conley01: Conley A, Mapes S, Corbin CJ, Greger D, Walters K, Trant J, Graham S (2001). "A comparative approach to structure-function studies of mammalian aromatases." J Steroid Biochem Mol Biol 79(1-5);289-97. PMID: 11850235

Corbin88: Corbin CJ, Graham-Lorence S, McPhaul M, Mason JI, Mendelson CR, Simpson ER (1988). "Isolation of a full-length cDNA insert encoding human aromatase system cytochrome P-450 and its expression in nonsteroidogenic cells." Proc Natl Acad Sci U S A 85(23);8948-52. PMID: 2848247

Ellis01a: Ellis JA, Wong ZY, Stebbing M, Harrap SB (2001). "Sex, genes and blood pressure." Clin Exp Pharmacol Physiol 28(12);1053-5. PMID: 11903314

Gurates02: Gurates B, Sebastian S, Yang S, Zhou J, Tamura M, Fang Z, Suzuki T, Sasano H, Bulun SE (2002). "WT1 and DAX-1 inhibit aromatase P450 expression in human endometrial and endometriotic stromal cells." J Clin Endocrinol Metab 87(9);4369-77. PMID: 12213901

Harada01: Harada N, Matsumoto T, Yoshimura N, Sakamoto H, Honda S (2001). "Analysis of transcriptional regulation of human breast aromatase by in vitro and in vivo studies." J Steroid Biochem Mol Biol 79(1-5);151-6. PMID: 11850219

Harada88: Harada N (1988). "Cloning of a complete cDNA encoding human aromatase: immunochemical identification and sequence analysis." Biochem Biophys Res Commun 156(2);725-32. PMID: 2973313

Harada92: Harada N, Ogawa H, Shozu M, Yamada K, Suhara K, Nishida E, Takagi Y (1992). "Biochemical and molecular genetic analyses on placental aromatase (P-450AROM) deficiency." J Biol Chem 267(7);4781-5. PMID: 1371509

Herrmann02: Herrmann BL, Saller B, Janssen OE, Gocke P, Bockisch A, Sperling H, Mann K, Broecker M (2002). "Impact of estrogen replacement therapy in a male with congenital aromatase deficiency caused by a novel mutation in the CYP19 gene." J Clin Endocrinol Metab 87(12);5476-84. PMID: 12466340

Hinshelwood01: Hinshelwood MM, Mendelson CR (2001). "Tissue-specific expression of the human CYP19 (aromatase) gene in ovary and adipose tissue of transgenic mice." J Steroid Biochem Mol Biol 79(1-5);193-201. PMID: 11850225

Kado02: Kado N, Kitawaki J, Obayashi H, Ishihara H, Koshiba H, Kusuki I, Tsukamoto K, Hasegawa G, Nakamura N, Yoshikawa T, Honjo H (2002). "Association of the CYP17 gene and CYP19 gene polymorphisms with risk of endometriosis in Japanese women." Hum Reprod 17(4);897-902. PMID: 11925378

Kamat01: Kamat A, Mendelson CR (2001). "Identification of the regulatory regions of the human aromatase P450 (CYP19) gene involved in placenta-specific expression." J Steroid Biochem Mol Biol 79(1-5);173-80. PMID: 11850222

Means89: Means GD, Mahendroo MS, Corbin CJ, Mathis JM, Powell FE, Mendelson CR, Simpson ER (1989). "Structural analysis of the gene encoding human aromatase cytochrome P-450, the enzyme responsible for estrogen biosynthesis." J Biol Chem 264(32);19385-91. PMID: 2808431

Means91: Means GD, Kilgore MW, Mahendroo MS, Mendelson CR, Simpson ER (1991). "Tissue-specific promoters regulate aromatase cytochrome P450 gene expression in human ovary and fetal tissues." Mol Endocrinol 5(12);2005-13. PMID: 1724289

Mor01: Mor G, Eliza M, Song J, Wiita B, Chen S, Naftolin F (2001). "17alpha-methyl testosterone is a competitive inhibitor of aromatase activity in Jar choriocarcinoma cells and macrophage-like THP-1 cells in culture." J Steroid Biochem Mol Biol 79(1-5);239-46. PMID: 11850230

Mukherjee02: Mukherjee TK, Dinh H, Chaudhuri G, Nathan L (2002). "Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: implications in atherosclerosis." Proc Natl Acad Sci U S A 99(6);4055-60. PMID: 11904449

Murakami01: Murakami H, Harada N, Sasano H (2001). "Aromatase in atherosclerotic lesions of human aorta." J Steroid Biochem Mol Biol 79(1-5);67-74. PMID: 11850209

Parish01: Parish D, Purohit A, Singh A, Rosankiewicz J, Ghilchik MW, Reed MJ (2001). "Peptide inhibition of cytokine-stimulated aromatase activity in breast tissue fibroblasts." J Steroid Biochem Mol Biol 79(1-5);165-72. PMID: 11850221

Richards02a: Richards JA, Petrel TA, Brueggemeier RW (2002). "Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells." J Steroid Biochem Mol Biol 80(2);203-12. PMID: 11897504

Shozu01: Shozu M, Sumitani H, Murakami K, Segawa T, Yang HJ, Inoue M (2001). "Regulation of aromatase activity in bone-derived cells: possible role of mitogen-activated protein kinase." J Steroid Biochem Mol Biol 79(1-5);61-5. PMID: 11850208

Simpson87: Simpson ER, Evans CT, Corbin CJ, Powell FE, Ledesma DB, Mendelson CR (1987). "Sequencing of cDNA inserts encoding aromatase cytochrome P-450 (P-450AROM)." Mol Cell Endocrinol 52(3);267-72. PMID: 3653507

Thompson74: Thompson EA, Siiteri PK (1974). "The involvement of human placental microsomal cytochrome P-450 in aromatization." J Biol Chem 249(17);5373-8. PMID: 4370479

Toda89: Toda K, Terashima M, Mitsuuchi Y, Yamasaki Y, Yokoyama Y, Nojima S, Ushiro H, Maeda T, Yamamoto Y, Sagara Y (1989). "Alternative usage of different poly(A) addition signals for two major species of mRNA encoding human aromatase P-450." FEBS Lett 247(2);371-6. PMID: 2541021

Toda90: Toda K, Terashima M, Kawamoto T, Sumimoto H, Yokoyama Y, Kuribayashi I, Mitsuuchi Y, Maeda T, Yamamoto Y, Sagara Y (1990). "Structural and functional characterization of human aromatase P-450 gene." Eur J Biochem 193(2);559-65. PMID: 2171939

Toda93: Toda K, Shizuta Y (1993). "Molecular cloning of a cDNA showing alternative splicing of the 5'-untranslated sequence of mRNA for human aromatase P-450." Eur J Biochem 213(1);383-9. PMID: 8477708

Yanase01: Yanase T, Mu YM, Nishi Y, Goto K, Nomura M, Okabe T, Takayanagi R, Nawata H (2001). "Regulation of aromatase by nuclear receptors." J Steroid Biochem Mol Biol 79(1-5);187-92. PMID: 11850224

Yang02e: Yang HJ, Shozu M, Murakami K, Sumitani H, Segawa T, Kasai T, Inoue M (2002). "Spatially heterogeneous expression of aromatase P450 through promoter II is closely correlated with the level of steroidogenic factor-1 transcript in endometrioma tissues." J Clin Endocrinol Metab 87(8);3745-53. PMID: 12161505

Yue01: Yue W, Berstein LM, Wang JP, Clark GM, Hamilton CJ, Demers LM, Santen RJ (2001). "The potential role of estrogen in aromatase regulation in the breast." J Steroid Biochem Mol Biol 79(1-5);157-64. PMID: 11850220

Zhou02b: Zhou XD, Cai WQ, Cao HW (2002). "[Relationship between level of sexual hormone in external blood and aromatase expression in cancer tissues of male patients with lung cancer]." Ai Zheng 21(3);259-62. PMID: 12451990


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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