Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0130)
DME Name Alcohol dehydrogenase class-II (ADH4), Homo sapiens DME Info
UniProt ID
ADH4_HUMAN
EC Number    EC: 1.1.1.105     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
CH-OH donor oxidoreductase
NAD/NADP oxidoreductase
EC: 1.1.1.105
Lineage    Species: Homo sapiens     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Interactome
Interactions between Xenobiotics and DME (XEOTIC)
      Fungicide(s), Herbicide(s) or Insecticide(s)
                  Fungicide Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Tebuconazole Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00957   XEOTIC Info Gene Form Protein
                                 Classification Fungicide
                                 DME Modulation Tebuconazole inhibits the drug-metabolizing activity of DME ADH4 [1]
                  Pesticide/Insecticide Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Dicrotophos Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01050   XEOTIC Info Gene Form mRNA
                                 Classification Pesticide/Insecticide
                                 DME Modulation Dicrotophos inhibits the expression of DME ADH4 [2]
                              Endosulfan Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01074   XEOTIC Info Gene Form Protein
                                 Classification Pesticide/Insecticide
                                 DME Modulation Endosulfan inhibits the drug-metabolizing activity of DME ADH4 [3]
      Health or Environmental Toxicant(s)
                  Acute Toxic Substance Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              1,4-naphthoquinone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01089   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation 1,4-naphthoquinone up-regulates the expression of DME ADH4 [4]
                              Formaldehyde Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01305   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Formaldehyde up-regulates the expression of DME ADH4 [5]
                              Oxyquinoline Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01419   XEOTIC Info Gene Form Protein
                                 Classification Acute Toxic Substance
                                 DME Modulation Oxyquinoline inhibits the expression of DME ADH4 and leads to decreasing the drug-metabolizing activity of this enzyme [6]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Benzo(a)pyrene Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00898   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Benzo(a)pyrene inhibits the expression of DME ADH4 [7]
                              Aflatoxin B1 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00806   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen-mycotoxin
                                 DME Modulation Aflatoxin B1 inhibits the expression of DME ADH4 [8], [9]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Lead Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01505   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation Lead up-regulates the expression of DME ADH4 [10]
                              Tris(1,3-dichloro-2-propyl)phosphate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01031   XEOTIC Info Gene Form Protein
                                 Classification Health Hazard
                                 DME Modulation Tris(1,3-dichloro-2-propyl)phosphate inhibits the drug-metabolizing activity of DME ADH4 [11]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:        7 Xenobiotics
                              Acetaminophen Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00217   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Acetaminophen inhibits the expression of DME ADH4 [12]
                              Bosentan Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00148   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Bosentan inhibits the drug-metabolizing activity of DME ADH4 [13]
                              Copper sulfate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00117   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Copper sulfate inhibits the expression of DME ADH4 [14]
                              Cyclosporine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00241   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cyclosporine inhibits the expression of DME ADH4 [15]
                              Estradiol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00090   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Estradiol inhibits the expression of DME ADH4 [16]
                              Fenofibrate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00035   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Fenofibrate inhibits the expression of DME ADH4 [17]
                              Valproic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00029   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Valproic acid inhibits the expression of DME ADH4 [18]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Sodium arsenite Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00632   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Sodium arsenite inhibits the expression of DME ADH4 [19]
References
1 Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
2 Molecular mechanisms of discrotophos-induced toxicity in HepG2 cells: The role of CSA in oxidative stress. Food Chem Toxicol. 2017 May;103:253-260.
3 Down-regulation of the expression of alcohol dehydrogenase 4 and CYP2E1 by the combination of alpha-endosulfan and dioxin in HepaRG human cells. Toxicol In Vitro. 2017 Dec;45(Pt 3):309-317.
4 Possible role of the exchange protein directly activated by cyclic AMP (Epac) in the cyclic AMP-dependent functional differentiation and syncytialization of human placental BeWo cells. Hum Reprod. 2010 Sep;25(9):2229-38.
5 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
6 Oxadiazon affects the expression and activity of aldehyde dehydrogenase and acylphosphatase in human striatal precursor cells: A possible role in neurotoxicity. Toxicology. 2019 Jan 1;411:110-121.
7 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
8 Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):176-87.
9 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
10 Correlations of gene expression with blood lead levels in children with autism compared to typically developing controls. Neurotox Res. 2011 Jan;19(1):1-13.
11 Species-specific differences in the inhibition of human and zebrafish 11beta-hydroxysteroid dehydrogenase 2 by thiram and organotins. Toxicology. 2012 Nov 15;301(1-3):72-8.
12 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
13 Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
14 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
15 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
16 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
17 Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
18 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
19 Inhibitory effects of nitric oxide on the expression and activity of aromatase in human granulosa cells. Mol Hum Reprod. 1999 May;5(5):396-401.

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