Showing metabocard for Diethylstilbestrol (HMDB0014400)

General function:

Involved in magnesium ion binding

Specific function:

Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.

Gene Name:

COMT

Uniprot ID:

P21964

Molecular weight:

30036.77

References

1. Engel LL, Weidenfield J, Merriam GR: Metabolism of diethylstilbestrol by rat liver: a preliminary report. J Toxicol Environ Health Suppl. 1976;1:37-44. [PubMed:11352 ]

General function:

Involved in sequence-specific DNA binding transcription factor activity

Specific function:

Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA- binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual

Gene Name:

ESR2

Uniprot ID:

Q92731

Molecular weight:

59215.8

References

1. Authors unspecified: Final amended report on the safety assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in cosmetic products. Int J Toxicol. 2008;27 Suppl 4:1-82. doi: 10.1080/10915810802548359. [PubMed:19101832 ]
2. Geistlinger TR, McReynolds AC, Guy RK: Ligand-selective inhibition of the interaction of steroid receptor coactivators and estrogen receptor isoforms. Chem Biol. 2004 Feb;11(2):273-81. [PubMed:15123288 ]

General function:

Involved in transferase activity, transferring hexosyl groups

Specific function:

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone.

Gene Name:

UGT1A1

Uniprot ID:

P22309

Molecular weight:

59590.91

Reactions

General function:

Involved in monooxygenase activity

Specific function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.

Gene Name:

CYP3A4

Uniprot ID:

P08684

Molecular weight:

57255.585

References

1. Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. [PubMed:21553654 ]

General function:

Involved in monooxygenase activity

Specific function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.

Gene Name:

CYP2C9

Uniprot ID:

P11712

Molecular weight:

55627.365

References

1. Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. [PubMed:21553654 ]

General function:

Involved in monooxygenase activity

Specific function:

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.

Gene Name:

CYP2E1

Uniprot ID:

P05181

Molecular weight:

56848.42

References

1. Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. [PubMed:21553654 ]

General function:

Involved in monooxygenase activity

Specific function:

Catalyzes the formation of aromatic C18 estrogens from C19 androgens.

Gene Name:

CYP19A1

Uniprot ID:

P11511

Molecular weight:

57882.48

References

1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

General function:

Involved in monooxygenase activity

Specific function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).

Gene Name:

CYP2C8

Uniprot ID:

P10632

Molecular weight:

55824.275

References

1. Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. [PubMed:21553654 ]

General function:

Involved in monooxygenase activity

Specific function:

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.

Gene Name:

CYP2A6

Uniprot ID:

P11509

Molecular weight:

56517.005

References

1. Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. [PubMed:21553654 ]

General function:

Involved in sequence-specific DNA binding transcription factor activity

Specific function:

Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Can activate the transcriptional activity of TFF1

Gene Name:

ESR1

Uniprot ID:

P03372

Molecular weight:

66215.4

References

1. Munoz G, Ovilo C, Estelle J, Silio L, Fernandez A, Rodriguez C: Association with litter size of new polymorphisms on ESR1 and ESR2 genes in a Chinese-European pig line. Genet Sel Evol. 2007 Mar-Apr;39(2):195-206. Epub 2007 Feb 17. [PubMed:17306201 ]
2. Dixon A, Wells CC, Singh S, Babayan R, Maric C: Renoprotective effects of a selective estrogen receptor modulator, raloxifene, in an animal model of diabetic nephropathy. Am J Nephrol. 2007;27(2):120-8. Epub 2007 Feb 15. [PubMed:17308373 ]
3. Hart SA, Snyder MA, Smejkalova T, Woolley CS: Estrogen mobilizes a subset of estrogen receptor-alpha-immunoreactive vesicles in inhibitory presynaptic boutons in hippocampal CA1. J Neurosci. 2007 Feb 21;27(8):2102-11. [PubMed:17314305 ]
4. Baron S, Escande A, Alberola G, Bystricky K, Balaguer P, Richard-Foy H: Estrogen receptor alpha and the activating protein-1 complex cooperate during insulin-like growth factor-I-induced transcriptional activation of the pS2/TFF1 gene. J Biol Chem. 2007 Apr 20;282(16):11732-41. Epub 2007 Feb 22. [PubMed:17317669 ]
5. Bains M, Cousins JC, Roberts JL: Neuroprotection by estrogen against MPP+-induced dopamine neuron death is mediated by ERalpha in primary cultures of mouse mesencephalon. Exp Neurol. 2007 Apr;204(2):767-76. Epub 2007 Jan 25. [PubMed:17320868 ]
6. Kwok KC, Cheung NH: Measuring binding kinetics of ligands with tethered receptors by fluorescence polarization and total internal reflection fluorescence. Anal Chem. 2010 May 1;82(9):3819-25. doi: 10.1021/ac1002245. [PubMed:20387803 ]
7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]