Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantification of intracellular and extracellular levels and production rates of reactive oxygen species is crucial to understanding their contribution to tissue pathophysiology. We measured basal rates of oxidant production and the activity of xanthine oxidase, proposed to be a key source of O2- and H2O2, in endothelial cells. Then we examined the influence of tumor necrosis factor-alpha and lipopolysaccharide on endothelial cell oxidant metabolism, in response to the proposal that these inflammatory mediators initiate vascular injury in part by stimulating endothelial xanthine oxidase-mediated production of O2- and H2O2. We determined a basal intracellular H2O2 concentration of 32.8 +/- 10.7 pM in cultured bovine aortic endothelial cells by kinetic analysis of aminotriazole-mediated inactivation of endogenous catalase. Catalase activity was 5.72 +/- 1.61 U/mg cell protein and glutathione peroxidase activity was much lower, 8.13 +/- 3.79 mU/mg protein. Only 0.48 +/- 0.18% of total glucose metabolism occurred via the pentose phosphate pathway. The rate of extracellular H2O2 release was 75 +/- 12 pmol.min-1.mg cell protein-1. Intracellular xanthine dehydrogenase/oxidase activity determined by pterin oxidation was 2.32 +/- 0.75 microU/mg with 47.1 +/- 11.7% in the oxidase form. Intracellular purine levels of 1.19 +/- 1.04 nmol hypoxanthine/mg protein, 0.13 +/- 0.17 nmol xanthine/mg protein, and undetectable uric acid were consistent with a low activity of xanthine dehydrogenase/oxidase. Exposure of endothelial cells to 1000 U/ml tumor necrosis factor (TNF) or 1 microgram/ml lipopolysaccharide (LPS) for 1-12 h did not alter basal endothelial cell oxidant production or xanthine dehydrogenase/oxidase activity. These results do not support a casual role for H2O2 in the direct endothelial toxicity of TNF and LPS.
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PMID:Responses of vascular endothelial oxidant metabolism to lipopolysaccharide and tumor necrosis factor-alpha. 156 24

Recently, some knowledge of metabolic pathways, rather than individual enzyme activities of M. leprae, is becoming available. Ultimately this may be useful in devising culture media for M. leprae. Knowledge restricted to individual reactions may be misleading. For instance, the detection of GlcNacase and beta-glucuronidase and the subcellular localization of hyaluronic acid led to attempts to cultivate M. leprae on hyaluronic-acid based medium. Subsequent investigations suggested that there was no pathway for the breakdown of hyaluronic acid in M. leprae. The biochemical pathways for breaking down glucose and glycerol seem to be complete, and thus similar to many bacteria, but there is an unusually high level of one enzyme, 6-phosphogluconate dehydrogenase (6PGDH). Although 6-phosphogluconate is oxidized by M. leprae, and this is an unusual activity, reflecting very high levels of 6PGDH, glycerol may be a preferable energy source (on the basis of rates of oxidation by suspensions) for M. leprae in attempts to cultivate the bacterium. The utilization of 6-phosphogluconate might be important for other aspects of M. leprae metabolism not yet investigated (e.g., pentose metabolism) or it may be an adaption, not needed in vitro, to its existence in host macrophages. Alternatively, its oxidation may be a way of rapidly generating NADPH at critical times for the bacterium. Other unusual activities which have been reported are the presence of an enzyme characteristic of chemoautotrophism , completely surprising in view of the biology of M. leprae. This report needs to be confirmed--some aspects, in fact, have failed to be confirmed. o-Diphenoloxidase activity is unique, among mycobacteria, to M. leprae, but there is still doubt over whether or not it is an enzymatic activity and its function is unknown. A transpeptidase which may be involved in cell wall synthesis, recently demonstrated in M. leprae, is a typical mycobacterial enzyme. It is now known that iron could be supplied to M. leprae in potential media in the form of ferriexochelin from M. neoaurum . Two "deletions" in the metabolic processes of M. leprae have been observed. Catalase appears to be absent in M. leprae; its addition to media stimulates the growth of some organisms since peroxides form in the bacteriological media . Purine synthesis de novo occurred at a very low rate compared with purine scavenging. Whether this is an adaption to growth in vivo is not known.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Metabolism in Mycobacterium leprae: its relation to other research on M. leprae and to aspects of metabolism in other mycobacteria and intracellular parasites. 614 38

Malignant hyperthermia (MH) is a severe familial disease in both the pig and the human, with 70% fatality when fully expressed in humans. MH produces rapid elevation of temperature in response to stresses, of which there are two general kinds: Societal or emotional stress, and chemical stressors. The most commonly encountered stressor is halothane, a general anesthetic in wide use. Besides large temperature increases, there occur some twenty symptoms. Much work in other laboratories has been concentrated on elevated CPK i the plasma. However, all the symptoms are consistent with a single disorder, namely oxidative damage, especially in membranes. A deficiency in the glutathione peroxidase (GPX) system is a prime factor, likely the molecular basis allowing abnormal oxidative damage in the MH pig. Catalase activities are normal in MH pigs, but they have only 20-50% normal GPX activities. The deficiency does not cause oxidative damage. It allows failure or protective mechanisms against it. The nonstressed MH animal exhibits less acute symptoms, e.g. enhanced red cell Heinz bodies, but such animals generally mature. Under stress, their inadequate protective mechanisms dependent on GPX are overwhelmed, resulting in gross symptoms and crisis. It is important to concentrate on the GPX system(s) and their adjacent pentose shunt metabolism. We propose that a deficiency in any of these two systems is the molecular basis of the disease. Many tissues are involve in MH, but the red cell obviously provides a convenient means for assay and for screening. This paper mainly pertains to porcine MH. However, preliminary work with humans indicates that human MH has a similar molecular basis.
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PMID:Malignant hyperthermia (MH): porcine erythrocyte damage from oxidation and glutathione peroxidase deficiency. 729 Nov 94

Various studies have shown the mutagenicity of red wine. The major mutagens identified in red wine have been flavonoids, i.e. rutin and its aglycone quercetin. Besides flavonoids, however, it has recently been reported that H2O2 may account for the mutagenicity of red wine in the L-Arabinose resistance test. In the present study we report on the role of flavonoids in the mutagenicity of red wine in the Ames assay. Different wines from Portugal and Spain have been tested after concentration in XAD-2 columns in strains TA98 and TA104 of Salmonella typhimurium concurrently with the determination of the respective content of quercetin by HPLC. A similar approach was used for pilot scale productions of red wines. In all cases quercetin could be demonstrated as the major mutagen in red wines. The levels of quercetin in finished wines and during the wine-making process showed a good fit with the levels of mutagenicity detected. Catalase had no effect whatsoever on the mutagenicity of wines in both TA98 and TA104. These results do not rule out a role for H2O2 in the mutagenicity of wines, detected in other genetic end-points, because H2O2 can be formed from the auto-oxidation of quercetin.
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PMID:Quercetin and the mutagenicity of wines. 845 Jul 68

The aim of this study was to determine whether neural cells exposed to beta amyloid (A beta) activate the pentose phosphate pathway (PPP), a critical oxidative stress defense mechanism. A beta stimulated H2O2 production in neural (B12) and non-neural (HepG2) cells and stimulated PPP activity, the source of the main intracellular reductant NADPH, in HepG2 cells (67% increase). Catalase blocked the A beta-induced increase in PPP, demonstrating that H2O2 mediated the increase in PPP activity. B12 cells showed no increase in PPP following A beta exposure. Fifty-five per cent of HepG2 cells but only 11.1% of B12 cells remained viable after A beta exposure. Lack of PPP activation may contribute to A beta cytotoxicity in neural calls and may lead to differences in survival between neural and non-neural cells.
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PMID:beta Amyloid does not activate the antioxidant pentose phosphate pathway within the B12 neural cell line. 917 13

The aim of the present study was to investigate the effects of treatment with antioxidant stobadine (ST) on the activities of enzymes related with pentose phosphate pathway and glutathione-dependent metabolism and the other markers of oxidative stress in brain and peripheral organs of diabetic rats, and to compare the effects of ST treatment alone with the effects of treatments with another antioxidant vitamin E and ST plus vitamin E. Rats were made diabetic by the injection of streptozotocin (STZ; 55 mg/kg IP), and, 2 days later, some control and diabetic rats were left untreated or treated with ST (24.7 mg/kg/day, orally), vitamin E (400-500 U/kg/day, orally), or both substances together. In the brain, although 6-phosphogluconate dehydrogenase activity (6-PGD) did not change, glucose-6-phosphate dehydrogenase activity (G-6PD) was markedly increased in diabetic rats compared with controls; only combined treatment with ST and vitamin E produced a partial prevention on this alteration. The aorta G-6PD and 6-PGD of diabetic rats were 52% and 36% of control values, respectively. Neither single treatments with each antioxidant nor their combination altered the G-6PD and 6-PGD in aorta of diabetic rats. Glutathione peroxidase (GSHPx) activity was increased by STZ-diabetes in brain, heart, and kidney. In diabetic brain, vitamin E alone or combination with ST kept GSHPx at normal levels. Diabetes-induced stimulation in GSHPx did not decrease in response to the treatment with vitamin E in heart and kidney, but was greatly prevented by ST alone. The activity of glutathione reductase (GR) was decreased in brain and heart of diabetic rats. The treatment with each antioxidant or with a combination of both agents completely prevented this deficiency and resulted in further activation of GR in diabetic tissues. Glutathione S-transferase (GST) activity did not significantly change in diabetic brain and aorta. GST was stimulated by all treatment protocols in the brain of diabetic rats and was depressed in aorta of control rats. Catalase (CAT) was activated in diabetic heart but depressed in diabetic kidney. Diabetes-induced abnormalities in CAT activity did not respond to vitamin E alone in heart, was moderately ameliorated by the treatment with this vitamin in kidney, and was completely prevented by ST alone in both tissues. Superoxide dismutase (SOD) activity of brain and heart was unchanged by the diabetes but inhibited in diabetic kidney after the treatment ST alone or ST plus vitamin E. The lipid peroxidation (MDA) was increased in diabetic brain and heart. ST or vitamin E alone partly prevented diabetes-induced increase in MDA in brain and heart; however, antioxidant combination achieved a completely amelioration in MDA of these tissues of diabetic rats. Kidney MDA levels were similar in control and untreated diabetic animals. ST and vitamin E treatments, when applied separately or together, significantly reduced kidney MDA in both control and diabetic rats; and the combined effect of antioxidants was greater than that of each alone. These results are consistent with the degenerative role of hyperglycemia on cellular reducing equivalent homeostasis and antioxidant defense, and provide further evidence that pharmacological intervention of different antioxidants may have significant implications in the prevention of the prooxidant feature of diabetes and protects redox status of the cells.
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PMID:Pentose phosphate pathway, glutathione-dependent enzymes and antioxidant defense during oxidative stress in diabetic rodent brain and peripheral organs: effects of stobadine and vitamin E. 1271 33

We have constructed a metabolic model describing the H2O2 elimination by mammalian cells. It comprises three compartments (medium, cytosol, and peroxisome) separated by cytoplasmic and peroxisomal membranes, and H2O2 moves across the membranes with different permeation rate constants. Catalase localizes to peroxisomes, while glutathione peroxidase (GPx) and GSH recycling system (glutathione reductase (GR) and the oxidative pentose phosphate pathway (PPP)) localize to cytosol. The rates of individual enzyme reactions were computed using the experimentally determined activities and rate equations known for mammalian enzymes. Using the model, the concentration dependence of H2O2 elimination rate was obtained by numerical simulation and was compared with experimental data obtained previously with cultured mammalian cells (fibroblasts, human umbilical vein endothelial cells (HUVEC), and PC12 cells). The model was shown to be able to reproduce the data well by assuming appropriate values for the permeability rate constants. The H2O2 permeability coefficients thus estimated for cytoplasmic and peroxisomal membranes were in the same order of magnitude, except that the value for cytoplasmic membrane of PC12 cell was significantly smaller. The results suggest that the membrane permeability is one of the rate-limiting factors in the H2O2 elimination by mammalian cells. Using the model and estimated parameter values, we have examined the rate-limiting enzyme of the metabolic system, as well as the intracellular H2O2 concentration under steady-state and non-steady-state conditions.
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PMID:A metabolic model describing the H2O2 elimination by mammalian cells including H2O2 permeation through cytoplasmic and peroxisomal membranes: comparison with experimental data. 1527 86

Sleep deprivation in humans is widely believed to impair health, and sleep is thought to have powerful restorative properties. The specific physical and biochemical factors and processes mediating these outcomes, however, are poorly elucidated. Sleep deprivation in the animal model produces a condition that eventually becomes highly lethal, lacks specific localization, and is reversible with sleep, implying mediation by a biochemical abnormality. Metabolic and immunological consequences of sleep deprivation point to a high potential for antioxidant imbalance. The objective, therefore, was to study glutathione content in the liver, heart, and lung, because glutathione is considered a major free radical scavenger that reflects the degree to which a tissue has been oxidatively challenged. We also investigated major enzymatic antioxidants, including catalase and glutathione peroxidase, as well as indexes of glutathione recycling. Catalase activity and glutathione content, which normally are tightly regulated, were both decreased in liver by 23-36% by 5 and 10 days of sleep deprivation. Such levels are associated with impaired health in other animal models of oxidative stress-associated disease. The decreases were accompanied by markers of generalized cell injury and absence of responses by the other enzymatic antioxidants under study. Enzymatic activities in the heart indicated an increased rate of oxidative pentose phosphate pathway activity during sleep deprivation. Recovery sleep normalized antioxidant content in liver and enhanced enzymatic antioxidant activities in both the liver and the heart. The present results link uncompensated oxidative stress to health effects induced by sleep deprivation and provide evidence that restoration of antioxidant balance is a property of recovery sleep.
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PMID:Antioxidant defense responses to sleep loss and sleep recovery. 1547 7

Campylobacter concisus is an emerging enteric pathogen that is associated with inflammatory bowel disease. Previous studies demonstrated that C. concisus is non-saccharolytic and hydrogen gas (H2) is a critical factor for C. concisus growth. In order to understand the molecular basis of the non-saccharolytic and H2-dependent nature of C. concisus growth, in this study we examined the pathways involving energy metabolism and oxidative stress defence in C. concisus. Bioinformatic analysis of C. concisus genomes in comparison with the well-studied enteric pathogen Campylobacter jejuni was performed. This study found that C. concisus lacks a number of key enzymes in glycolysis, including glucokinase and phosphofructokinase, and the oxidative pentose phosphate pathway. C. concisus has an incomplete tricarboxylic acid cycle, with no identifiable succinyl-CoA synthase or fumarate hydratase. C. concisus was inferred to use fewer amino acids and have fewer candidate substrates as electron donors and acceptors compared to C. jejuni. The addition of DMSO or fumarate to media resulted in significantly increased growth of C. concisus in the presence of H2 as an electron donor, demonstrating that both can be used as electron acceptors. Catalase, an essential enzyme for oxidative stress defence in C. jejuni, and various nitrosative stress enzymes, were not found in the C. concisus genome. Overall, C. concisus is inferred to have a non-saccharolytic metabolism in which H2 is central to energy conservation, and a narrow selection of carboxylic acids and amino acids can be utilised as organic substrates. In conclusion, this study provides a molecular basis for the non-saccharolytic and hydrogen-dependent nature of C. concisus energy metabolism pathways, which provides insights into the growth requirements and pathogenicity of this species.
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PMID:Analyses of energy metabolism and stress defence provide insights into Campylobacter concisus growth and pathogenicity. 3216 25