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)

1. Ethanol metabolism in slices or homogenates of transplantable hepatocellular carcinoma HC-252 (HC-252) was 50 to 60% of the rate found in host liver slices or homogenates when they were expressed per gram of tissue wet weight and 70 to 80% of the liver when the rates were expressed per milligram of tissue protein. At 10 mM ethanol, the activities of alcohol dehydrogenase in tumor and liver supernatants were comparable. 2. Tumor microsomes did not oxidize ethanol in the presence of a NADPH-generating system, indicating the absence of the microsomal ethanol-oxidizing system and catalase-mediated peroxidation of ethanol. The HC-252 microsomes were contaminated with catalase, and acetaldehyde production occurred in the presence of a H2O2-generating system (xanthine oxidase). The virtual absence of ethanol oxidation and drug metabolism (aminopyrine demethylase and aniline hydroxylase) in HC-252 microsomes may be due to the low activities of NADPH-cytochrome c reductase, NADPH oxidase, and NADPH-dependent oxygen uptake. 3. Microsomal oxidation of ethanol was present in Morris hepatoma 5123C, a well-differentiated tumor of intermediate growth rate, while activity was negligible in microsomes from Morris hepatoma 7288CTC, a less differentiated tumor. Microsomal NADPH oxidase was present in the well differentiated tumor 5123C but was lacking in the less differentiated tumor 7288CTC. Several microsomal, mitochondrial, and cytosolic properties of HC-252 are similar to those of Morris hepatoma 7288CTC but differ from those of the more differentiated 5123C tumor and normal liver. 4. The content of mitochondrial protein in HC-252 was only 25% that of liver, and oxygen consumption per gram of tumor was only 28% that of the liver. When corrected for the mitochondrial protein content, oxygen uptake in tumor HC-252 and liver homogenates was comparable. Isolated tumor and liver mitochondria displayed comparable State 4 and 3 rates of oxygen consumption with succinate and glutamate as substrates. The activities of the reconstituted malate-aspartate and alpha-glycerophosphate shuttles were only slightly lower in isolated HC-252 mitochondria compared to liver mitochondria, when shuttles were reconstituted with purified enzymes. 5. Antimycin inhibited alcohol metabolism,and pyruvate stimulated alcohol metabolism, much less in tumor slices than in liver slices, suggesting the presence of an augmented mitochondria-independent, cytosolic mechanism for oxidizing reducing equivalents in the tumor. These factors suggest that oxidation of NADH is the limiting factor in ethanol metabolism. Whereas, in the liver mitochondrial reoxidation is predominant, in HC-252, cytosolic reoxidation of NADH also plays a major role.
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PMID:Ethanol metabolism by a transplantable hepatocellular carcinoma. Role of microsomes and mitochondria. 13 37

Xanthine oxidase was decreased 2- to 10-fold in all examined rat hepatomas irrespective of the malignancy; growth rate and degrees of histological differentiation of the neoplasms. The affinity to substrate (KM=6-8 muM) and the pH optimum (8.0) of the liver and hepatoma enzymes were the same. The reprogramming of gene expression, as manifested in the decreased activity of this key purine metabolizing enzyme, appears to be specific to neoplastic transformation. Since glutamine PRPP amidotransferase activity was increased but the opposing enzyme, xanthine oxidase, was decreased in all the hepatomas, the reprogramming of gene expression results in an imbalance that favors synthesis against catabolism. This enzymatic imbalance should confer selective advantages to the cancer cells.
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PMID:Malignant transformation-linked imbalance: decreased xanthine oxidase activity in hepatomas. 17 60

The behavior of the rate-limiting enzyme of purine catabolism, xanthine oxidase (EC 1.2.3.2); was examined in normal liver, in 17 hepatomas of different growth rates, and in rapidly growing differentiating and regenerating liver. Xanthine oxidase activity was measured in the supernatant fluid prepared by centrifugation of 5% homogenates at 100,000 X g for 30 min. There was no uricase activity in the supernatant fluid. The affinity of xanthine oxidase to xanthine was similar in normal liver and in slow- and rapidly growing hepatomas (Km=6 to 8 muM), and theoptimum pH was 8.0; at pH 7.4, the activity was 80% of that at the pH optimum. A standard assay was worked out for the liver and hepatoma systems; the enzyme activity was linear during 60-min incubation and proportionate with amounts of protein added over a range of 0.5 to 3.0 mg. Xanthine oxidase specific activity was 9 times higher in small intestine than in liver. Activities in lung, spleen, kidney, heart, testes, and thymus were 67, 59, 21, 19, 8, and 8%, and in skeletal muscle, brain, and bone marrow activities were 5% of that of the liver. In regenerating liver, xanthine oxidase activity was not changed from that of the liver of sham-operated controls up to 96 hr after operation. The activity of the average differentiating liver cell was less than 5% of that of adult liver during the first week after birth. At postnatal ages of 18, 25, 30 and 40 days, the activity rose to 18, 46, 76, and 94%, respectively, of that of the adult liver. In starvation, hepatic xanthine oxidase activity per cell was preferentially depleted as compared to the decline in protein concentration. Upon refeeding, the enzymatic activity was restored more slowly than the protein content. Since xanthine oxidase activity was decreased in all examined hepatomas, including the slowest-growing, well-differentiated neoplasms, the altered activity of this enzyme appears to be.linked with neoplastic transformatiobosyl 1-pyrophosphate amidotransferase (EC 2.4.2.14), was increassed in the hepatomas, the reprogramming of gene expression results in an imbalance that favors the synthetic over the catabolic potential. This enzymatic imbalance should confer selective advantages to the cancer cells.
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PMID:Imbalance of purine metabolism in hepatomas of different growth rates as expressed in behavior of xanthine oxidase (EC 1.2.3.2). 18 29

Lipid peroxidation of microsomal membranes isolated from rat liver, and Morris hepatomas 9618A (slow-growing) and 3924A (fast-growing) was induced by superoxide radicals generated by the action of xanthine oxidase on xanthine. The peroxidation, measured as malondialdehyde and lipid hydroperoxide formation, was optimized with regard to iron concentration and chelation of iron by ADP. In such conditions hepatoma microsomes catalyze lower rates of lipid peroxidation than the normal counterpart. However, while microsomes from hepatoma 3924A show a marked decrease in both the malondialdehyde and hydroperoxide production rates, microsomes from hepatoma 9618A differ moderately from the control, mainly in the long-term production of hydroperoxides. It is also reported here that the 9618A microsomes partially lack cytochrome P-450 (about 40% deficiency), but they have a fatty acid composition similar to that of control. No differences were found in the content of vitamin E between normal and hepatoma 3924A microsomes. Moreover, induction of vitamin E deficiency in hepatoma 3924A microsomes does not influence the rate of either malondialdehyde or lipid hydroperoxide production. On the basis of these results and previous data on the lipid composition of hepatoma 3924A microsomes it is proposed that the high resistance to superoxide-dependent lipid peroxidation of hepatoma 3924A microsomes is related to the low substrate availability rather than the content of membrane antioxidants; and a limitation only in the propagation phase characterizes the hepatoma 9618A microsomal lipid peroxidation and would be due to the partial deficiency of the endogenous propagating agent, cytochrome P-450.
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PMID:Superoxide-dependent lipid peroxidation and vitamin E content of microsomes from hepatomas with different growth rates. 298 56

Effect of superoxide radical (O2-) produced extracellularly by hypoxanthine (HX) and xanthine oxidase (XO) on invasive capacity of rat ascites hepatoma cells was studied. Invasive capacity was estimated in vitro by counting the number of tumor cell colonies penetrated underneath cultured mesothelial cell monolayer. When the tumor cells had been treated with non-toxic doses of HX and XO, the formation of penetrated colonies increased with increasing concentrations of XO. This increment was completely inhibited by scavengers of active oxygen radicals, superoxide dismutase (SOD) in combination with catalase (CAT) added simultaneously at the time of HX-XO treatment.
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PMID:Superoxide radical potentiates invasive capacity of rat ascites hepatoma cells in vitro. 301 47

Pretreatment of Chinese hamster ovary (CHO) or H4 (rat hepatoma) cells with low non-toxic doses of H2O2 or xanthine-xanthine oxidase renders the cells more resistant to the toxic effect of H2O2 and gamma-rays. This increased resistance is observed both in exponentially growing and in plateau-phase cells. Cells pretreated with xanthine-xanthine oxidase are less mutated than control cultures when challenged with ionizing radiation. The number of DNA single-strand breaks (measured by nucleoid sedimentation) induced by a high dose of gamma-rays or H2O2 is lower in cells pretreated with xanthine-xanthine oxidase compared to control cultures. However, the pretreatment does not modify the rate of DNA single-strand breaks rejoining in cells challenged with H2O2 or gamma-rays. The catalase activity is not modified in pretreated cells, but the superoxide dismutase activity is increased about 2-fold.
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PMID:Pretreatment with oxygen species increases the resistance of mammalian cells to hydrogen peroxide and gamma-rays. 341 50

Xanthine dehydrogenase (EC 1.1.1.204), the rate-limiting enzyme of purine degradation, was purified 642-fold to homogeneity from liver of male Wistar rats. Antibody was generated to the purified enzyme in white rabbits and was partially purified. For the immunotitration a radioassay of high sensitivity was developed to determine low enzyme activities. Titration curves with the antibody showed that the xanthine dehydrogenase enzyme protein amounts in slowly growing hepatoma 20 and rapidly growing hepatoma 3924A were 34 and 4% of those of normal liver, which was in good agreement with the decrease in the activity of the enzyme to 33 and 2%, respectively. The contents of flavin adenine dinucleotide, the essential cofactor of the enzyme, in the immunoprecipitates in hepatomas 20 and 3924A were 27 and 4% of that of the normal liver. This is the first report to provide immunological evidence that a decreased enzyme activity in rat hepatomas, that of xanthine dehydrogenase, was due to a decrease in the enzyme protein amount. The markedly decreased xanthine dehydrogenase activity and amount have far-reaching biochemical and pharmacological implications for the tumors.
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PMID:Decreased concentration of xanthine dehydrogenase (EC 1.1.1.204) in rat hepatomas. 346 Jun 92

The hepatocarcinogen acetamide, in single doses of 100 and 400 mg/kg b.wt., was shown to act as an initiator in a dose-dependent fashion in rat liver using the Solt-Farber method. Acetamide and its putative metabolite N-hydroxy-acetamide did not cause liver necrosis in single dose experiments. Acetamide showed no evidence for genotoxicity in tests for mutations in Salmonella typhimurium, for DNA damage in rat hepatoma cells or for DNA repair in isolated rat hepatocytes. In contrast, N-hydroxy-acetamide displayed genotoxic activity in all 3 test systems. Neither acetamide nor N-hydroxy-acetamide induced transformation of primary Syrian hamster embryo cells or gave evidence of inhibition of metabolic cooperation in V79 cells. Radiolabelled acetamide and N-hydroxy-acetamide were not bound covalently to proteins in the presence of various metabolic activation systems (microsomes plus NADPH or xanthine/xanthine oxidase, cytosol or cytosol plus acetyl CoA or proline plus ATP). N-Hydroxy-acetamide was cytotoxic to monolayers of isolated hepatocytes at concentrations above 2.5 mM. This cytotoxicity was increased after diethyl maleate treatment, but N-hydroxy-acetamide did not deplete cellular glutathione. A HPLC system was developed for the separation and quantification of acetamide, N-hydroxy-acetamide and acetic acid. No significant excretion of N-hydroxy-acetamide or acetic acid in the urine could be demonstrated after treatment of rats with 100 or 1,000 mg/kg b.wt. of acetamide. The underlying mechanism for the observed initiating effect of acetamide is obscure.
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PMID:Studies on the mechanism of acetamide hepatocarcinogenicity. 355 Jul 69

Activities of glucose-6-phosphatase, fructose 1,6-diphosphatase, ornithine transcarbamylase, arginase and xanthine oxidase were measured in thioacetamide induced primary hepatoma and its tumour cell suspension. It was observed that the percentage decrease in the activities of all the enzymes in tumour cell suspension was far more than that observed in tumour tissue. However, in these studies no qualitative difference was observed between the parenchymal cells and the tumour cells.
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PMID:Enzyme studies on tumour cell suspensions. 432 28

Experiments were carried out to determine if the difference in rates of cell proliferation between normal and neoplastic cells may be related to altered levels of oxidative enzymes. Assays were performed using homogenates from hepatocellular carcinoma HC-252, a rapidly growing and moderately well-differentiated tumor; from normal liver; and from the liver of the tumor-bearing ACI rat. Results of the mitochondrial enzymes indicated that the activities of cytochrome oxidase and succinate dehydrogenase were 3-fold lower in tumor homogenates than in liver homogenates. Monoamine oxidase activity could not be detected in HC-252; mixing experiments indicated no inhibitor was present in HC-252. Activities of th peroxisomal enzymes, urate oxidase, D-amino acid oxidase, and L-alpha-hydroxy acid oxidase were either undetected in the tumor or were 12-fold lower than in liver homogenates. The activity of xanthine oxidase, a cytoplasmic enzyme, was 5- to 6-fold lower in the tumor. Catalase activity in the tumor was also lower than in liver; this may be indicative of a lower oxidative environment at the cellular level. These enzyme activities of the liver of tumor-bearing rats were in the same range as those of normal rat liver, except that D-amino acid oxidase activity was slightly lower, and catalase activity was markedly lower and varied in a wide range. These results show an inverse correlation between the activities of oxygen-utilizing enzymes and rates of proliferation of one tumor line and its control. The possible implications of these results in neoplasia, cell proliferation, and cellular aging are discussed.
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PMID:Oxidoreductase activities in normal rat liver, tumor-bearing rat liver, and hepatoma HC-252. 689 80


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