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MeSH Review

Metabolic Detoxication, Phase II

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Disease relevance of Metabolic Detoxication, Phase II


High impact information on Metabolic Detoxication, Phase II

  • During postembryonic stages, SKN-1 regulates a key Phase II detoxification gene through constitutive and stress-inducible mechanisms in the ASI chemosensory neurons and intestine, respectively [5].
  • The widespread expression of MRP in tissues, combined with its ability to transport both lipophilic xenobiotics and the products of phase II detoxification, indicates that the transporter represents a widespread and remarkably versatile cellular defense mechanism [6].
  • Nrf2 is a transcription factor that regulates important antioxidant and phase II detoxification genes [7].
  • A major protective mechanism against oxidizing substances capable of damaging DNA integrity and initiating carcinogenesis is the induction of phase II detoxification and antioxidant enzymes by chemopreventive agents [8].
  • An imbalance between phase I drug metabolism [e.g., cytochrome P450 (CYP)] and phase II detoxification [e.g., glutathione S-transferase (GST)] may contribute to the development of these diseases [9].

Biological context of Metabolic Detoxication, Phase II


Anatomical context of Metabolic Detoxication, Phase II


Associations of Metabolic Detoxication, Phase II with chemical compounds


Gene context of Metabolic Detoxication, Phase II


  1. Binding of hematin by a new class of glutathione transferase from the blood-feeding parasitic nematode Haemonchus contortus. van Rossum, A.J., Jefferies, J.R., Rijsewijk, F.A., LaCourse, E.J., Teesdale-Spittle, P., Barrett, J., Tait, A., Brophy, P.M. Infect. Immun. (2004) [Pubmed]
  2. An association between idiopathic Parkinson's disease and polymorphisms of phase II detoxification enzymes: glutathione S-transferase M1 and quinone oxidoreductase 1 and 2. Harada, S., Fujii, C., Hayashi, A., Ohkoshi, N. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  3. Sulfotransferase 1A1 (SULT1A1) polymorphism, PAH-DNA adduct levels in breast tissue and breast cancer risk in a case-control study. Tang, D., Rundle, A., Mooney, L., Cho, S., Schnabel, F., Estabrook, A., Kelly, A., Levine, R., Hibshoosh, H., Perera, F. Breast Cancer Res. Treat. (2003) [Pubmed]
  4. Hemolytic anemia and induction of phase II detoxification enzymes by diprop-1-enyl sulfide in rats: dose-response study. Munday, R., Munday, C.M., Munday, J.S. J. Agric. Food Chem. (2005) [Pubmed]
  5. SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. An, J.H., Blackwell, T.K. Genes Dev. (2003) [Pubmed]
  6. ATP-dependent uptake of natural product cytotoxic drugs by membrane vesicles establishes MRP as a broad specificity transporter. Paul, S., Breuninger, L.M., Tew, K.D., Shen, H., Kruh, G.D. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  7. Nrf2 is increased by CYP2E1 in rodent liver and HepG2 cells and protects against oxidative stress caused by CYP2E1. Gong, P., Cederbaum, A.I. Hepatology (2006) [Pubmed]
  8. Activation of the Nrf2-ARE signaling pathway: a promising strategy in cancer prevention. Giudice, A., Montella, M. Bioessays (2006) [Pubmed]
  9. Polymorphic expression of the glutathione S-transferase P1 gene and its susceptibility to Barrett's esophagus and esophageal carcinoma. van Lieshout, E.M., Roelofs, H.M., Dekker, S., Mulder, C.J., Wobbes, T., Jansen, J.B., Peters, W.H. Cancer Res. (1999) [Pubmed]
  10. The Keap1 BTB/POZ dimerization function is required to sequester Nrf2 in cytoplasm. Zipper, L.M., Mulcahy, R.T. J. Biol. Chem. (2002) [Pubmed]
  11. Conformational stability of pGEX-expressed Schistosoma japonicum glutathione S-transferase: a detoxification enzyme and fusion-protein affinity tag. Kaplan, W., Hüsler, P., Klump, H., Erhardt, J., Sluis-Cremer, N., Dirr, H. Protein Sci. (1997) [Pubmed]
  12. Prognostic significance of glutathione S-transferase-pi in invasive breast cancer. Huang, J., Tan, P.H., Thiyagarajan, J., Bay, B.H. Mod. Pathol. (2003) [Pubmed]
  13. A phase II detoxification enzyme inducer from lemongrass: identification of citral and involvement of electrophilic reaction in the enzyme induction. Nakamura, Y., Miyamoto, M., Murakami, A., Ohigashi, H., Osawa, T., Uchida, K. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  14. Induction of the protective antioxidant response element pathway by 6-hydroxydopamine in vivo and in vitro. Jakel, R.J., Kern, J.T., Johnson, D.A., Johnson, J.A. Toxicol. Sci. (2005) [Pubmed]
  15. Maternal smoking and the risk of orofacial clefts: Susceptibility with NAT1 and NAT2 polymorphisms. Lammer, E.J., Shaw, G.M., Iovannisci, D.M., Van Waes, J., Finnell, R.H. Epidemiology (Cambridge, Mass.) (2004) [Pubmed]
  16. Induction of human NAD(P)H:quinone oxidoreductase (NQO1) gene expression by the flavonol quercetin. Valerio, L.G., Kepa, J.K., Pickwell, G.V., Quattrochi, L.C. Toxicol. Lett. (2001) [Pubmed]
  17. Glutathione S-transferase expression in hepatitis B virus-associated human hepatocellular carcinogenesis. Zhou, T., Evans, A.A., London, W.T., Xia, X., Zou, H., Shen, F., Clapper, M.L. Cancer Res. (1997) [Pubmed]
  18. A sulforaphane analogue that potently activates the Nrf2-dependent detoxification pathway. Morimitsu, Y., Nakagawa, Y., Hayashi, K., Fujii, H., Kumagai, T., Nakamura, Y., Osawa, T., Horio, F., Itoh, K., Iida, K., Yamamoto, M., Uchida, K. J. Biol. Chem. (2002) [Pubmed]
  19. Cyclopentenone prostaglandins as potential inducers of phase II detoxification enzymes. 15-deoxy-delta(12,14)-prostaglandin j2-induced expression of glutathione S-transferases. Kawamoto, Y., Nakamura, Y., Naito, Y., Torii, Y., Kumagai, T., Osawa, T., Ohigashi, H., Satoh, K., Imagawa, M., Uchida, K. J. Biol. Chem. (2000) [Pubmed]
  20. Chemopreventive activity of oltipraz. Clapper, M.L. Pharmacol. Ther. (1998) [Pubmed]
  21. FQR1, a novel primary auxin-response gene, encodes a flavin mononucleotide-binding quinone reductase. Laskowski, M.J., Dreher, K.A., Gehring, M.A., Abel, S., Gensler, A.L., Sussex, I.M. Plant Physiol. (2002) [Pubmed]
  22. Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. Lee, J.M., Calkins, M.J., Chan, K., Kan, Y.W., Johnson, J.A. J. Biol. Chem. (2003) [Pubmed]
  23. Examination of human tissue cytosols for expression of sulfotransferase isoform 1A2 (SULT1A2) using a SULT1A2-specific antibody. Nowell, S., Green, B., Tang, Y.M., Wiese, R., Kadlubar, F.F. Mol. Pharmacol. (2005) [Pubmed]
  24. Increased frequency of wild-type arylamine-N-acetyltransferase allele NAT2*4 homozygotes in Portuguese patients with colorectal cancer. Gil, J.P., Lechner, M.C. Carcinogenesis (1998) [Pubmed]
  25. Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Bai, J., Lai, L., Yeo, H.C., Goh, B.C., Tan, T.M. Int. J. Biochem. Cell Biol. (2004) [Pubmed]
  26. Structure and in vitro substrate specificity of the murine multidrug resistance-associated protein. Paul, S., Belinsky, M.G., Shen, H., Kruh, G.D. Biochemistry (1996) [Pubmed]
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