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

The metabolism of 8-14C-theophylline (14C-Theo) was investigated in vivo and in vitro in the rat. In vivo, 14C-Theo at an initial blood concentration of 10muM was metabolized to at least two different metabolites, 1,3-dimethyl uric acid and 1-methyl uric acid. The biological half-life of the 8-14C-Theo (6 +/- 1.5 hours) was determined from the urinary excretion of radioactivity. Ten days of oral pretreatment of rats with theophylline resulted in a faster rate of metabolism of both 14C-Theo and zoxazolamine. In vitro metabolism of 14C-Theo was investigated in order to identify the enzyme(s) responsible for theophylline metabolism. A tissue survey utilizing tissue slices demonstrated that the metabolism is localized only in the liver since slices of heart, lung, intestine, brain, adrenals, kidney or spleen did not metabolize 14C-Theo. 14C-Theo metabolism in the liver was localized in the subcellular fraction of microsomes and not in the mitochondria or cytosol. 14C-Theo metabolism by liver slices or liver microsomes was inhibited by typical liver microsomal inhibitors such as 2-diethylaminoethyl-2,2-diphenylvalerate (SKF 525-A) and 3-methyl-4-methylaminoazobenzene. 14C-Theo metabolism in liver slices was increased by the liver microsomal-inducing agents, phenobarbital and 3-methylcholanthrene. 3-Methylcholanthrene also increased 14C-Theo metabolism by the liver microsomal fraction. One of the metabolites, 1-methylxanthine, generated by the microsomal system, is a substrate for xanthine oxidase, and its conversion to 1-methyl uric acid by xanthine oxidase was blocked by allopurinol. 14C-Theo per se was shown not to be a substrate for liver xanthine oxidase or aldehyde oxidase. These results indicate that Theo per se is metabolized by the liver microsomal system and not by liver xanthine oxidase or aldehyde oxidase.
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PMID:Theophylline metabolism by the rat liver microsomal system. 124 12

The effect of metabolic activation on the mutagenicity of nitrodibenzofurans (NDF) by rat liver S9 was evaluated with S. typhimurium tester strains. Except for 1-nitrodibenzofuran (NDF), five tested NDFs were mutagenic in strains TA98 and TA98/1,8-DNP6 without S9 mix but were not mutagenic in strain TA98NR. NDFs mutagenized strain TA98NR with S9 mix, and the NAD(P)H system plus 3-methylcholanthrene-induced S9 (3-MC-S9) was the most effective. The specificity of S9 enzyme(s) participating in the activation of NDFs was different from that of endogenous enzyme(s) in strain TA98, i.e., the order of mutagenic potency of NDFs in strain TA98 without S9 mix was 2,8- = 2,7-->3-->2-->4-->1-nitrated dibenzofuran and 2-NDF and 2,8-dinitrodibenzofuran (DNDF) were more mutagenic than 3-NDF and 2,7-DNDF, respectively, in strain TA98NR with S9 mix. The mutagenic potency of 2-NDF, 4-NDF, 2,7-DNDF and 2,8-DNDF in strain TA98NR with S9 mix was stronger than those in strain TA98 without S9 mix and the cytosolic fraction of the 3-MC-S9 accounted for more of the activation than the microsomal fraction. Studies with electron donors and inhibitors indicated that xanthine oxidase and/or NAD(P)H-quinone oxido-reductase (NQOR) participated in the activation of NDFs. The mutagenic potency of NDFs in strain TA98NR with S9 mix (3-MC-S9) was reflected in the induction of NQOR by pretreatment of rats with 3-MC.
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PMID:Metabolic activation of nitrodibenzofurans by rat liver in Salmonella/mutagenicity test. 752 Oct 8

The effect of rat liver S9 on the mutagenicity of 10 nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) was evaluated with Salmonella typhimurium TA98NR using S9 from phenobarbital-, 3-methylcholanthrene (MC)-, beta-naphthoflavone- and polychlorobiphenyl-treated and untreated rats. 2-Nitrofluorene (2-NFI), 2-nitrofluoren-9-one (2-NFlone), 2-nitrocarbazole (2-NCz), 3-NCz, 2-nitrodibenzothiophene (2-NDBT), 2-nitro-6H-dibenzo[b,d]pyran-6-one (2-NDBP) and 3-NDBP were metabolically activated by one or more of the S9 fractions, and the highest enhancement of the mutagenic potency of nitro-PAHs was observed with 3-MC-induced S9. Only in the case of 3-NFlone was the mutagenicity in strain TA98NR decreased by the addition of S9, regardless of S9 induction. 2-NDBP was most efficiently activated among nitro-PAHs tested by all S9 fractions used. The cytosolic fraction of S9 accounted for more of the activation of 2-NDBP than the microsomal fraction. NADH and NADPH were the most effective electron donors on the activation of 2-NDBP by S9, 2-NDBP was also metabolically activated by NADH plus commercial preparations of xanthine oxidase. These activations of 2-NDBP were inhibited by allopurinol, indicating that cytosolic xanthine oxidase in rat liver S9 participates in the activation of 2-NDBP. The potency of 2- and 3-NDBP isomers as base-substitution mutagens was also enhanced by S9. In the presence of S9, both compounds showed the highest mutagenicity in strain TA7005 (C.G-->A.T) followed by strains TA7004 (G.C-->A.T), TA7006 (C.G-->G.C) and TA7002 (T.A-->A.T), and this mutation specificity was similar to that without S9, indicating that the mechanism of mutagenesis caused by NDBP isomers with S9 is similar to that without S9.
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PMID:Metabolic activation of 2- and 3-nitrodibenzopyranone isomers and related compounds by rat liver S9 and the effect of S9 on the mutational specificity of nitrodibenzopyranones. 902 93