Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dihydrodiol dehydrogenase (DD; EC 1.3.1.20) catalyzes the oxidation of polycyclic aromatic hydrocarbon (PAH) trans-dihydrodiols (proximate carcinogens) to catechols which rapidly autoxidize to yield o-quinones (Smithgall, T. E., Harvey, R. G., and Penning, T. M. (1988) J. Biol. Chem 263, 1814-1820). Although this pathway suppresses the formation of the PAH anti- and syn-diol epoxides (ultimate carcinogens), the process of autoxidation is anticipated to yield reactive oxygen species (ROS). We now show that the NADP+ dependent oxidation of (+/-)-trans-1,2-dihydroxy-1,2-dihydronaphthalene (Npdiol) and (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (Bpdiol) catalyzed by homogeneous DD is accompanied by the consumption of molecular oxygen and the production of H2O2. With both trans-dihydrodiol substrates, oxygen consumption was stoichiometric with H2O2 production consistent with the reaction: QH2 + O2 = H2O2 + Q, where QH2 is the catechol and Q is the o-quinone. Using Npdiol or Bpdiol as substrates, a burst of superoxide anion production is catalyzed by DD which can be detected as the rate of cyt c reduction that is inhibited by superoxide dismutase. Using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as spin-trapping agent, secondary spin adducts corresponding to DMPO-CH3 were formed during the enzymatic oxidation of Npdiol and Bpdiol. The formation of the CH3. radical arises from the OH. attack of DMSO, which was used as cosolvent. These spin adducts were attenuated by superoxide dismutase and catalase, implying that O2-. and H2O2 are obligatory for the formation of DMPO-CH3. It is proposed that O2-. is the radical that propagates autoxidation and that the resultant H2O2 undergoes Fenton chemistry to produce the OH. radical. Identical spin adducts were observed using a superoxide anion generating system (hypoxanthine/xanthine oxidase) and DMPO as spin-trapping agent in the presence of DMSO. The ability of DD to generate ROS during the oxidation of PAH trans-dihydrodiols (proximate carcinogens) may have important implications for tumor initiation and promotion.
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PMID:Generation of reactive oxygen species during the enzymatic oxidation of polycyclic aromatic hydrocarbon trans-dihydrodiols catalyzed by dihydrodiol dehydrogenase. 892 21

Curcumin is a major component of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animals as indicated by its ability to block colon tumor initiation by azoxymethane and skin tumor promotion induced by phorbol ester TPA. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase. Curcumin is also a potent inhibitor of protein kinase C, EGF-receptor tyrosine kinase and IkappaB kinase. Subsequently, curcumin inhibits the activation of NFkappaB and the expressions of c-jun, c-fos, c-myc and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction pathways in the target cells. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin-glucuronide, dihydro-curcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are major metabolites of curcumin in mice.
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PMID:Recent studies on the biofunctions and biotransformations of curcumin. 1123 76

Curcumin is a major component of the Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animals as indicated by its ability to block colon tumor initiation by azoxymethane and skin tumor promotion induced by phorbol ester TPA. Recently, curcumin has been considered by oncologists as a potential third generation cancer chemopreventive agent, and clinical trials using it have been carried out in several laboratories. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes, such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase. Curcumin is also a potent inhibitor of protein kinase C, EGF-receptor tyrosine kinase and IkappaB kinase. In addition, curcumin inhibits the activation of NFkappaB and the expression of c-jun, c-fos, c-myc and iNOS. It is proposed that curcumin may suppress tumor promotion by blocking signal transduction pathways in the target cells. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin, and these compounds were subsequently convened into monoglucuronide conjugates. The experimental results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are major metabolites of curcumin in mice.
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PMID:Mechanisms of cancer chemoprevention by curcumin. 1137 Jul 61