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)

Chloroquine (1, 5 and 10 mg/kg), given in acute and in chronic (7 and 15 days) treatment schedules, caused characteristic alterations in the lysosomal enzyme system, antioxidant enzymes, NADPH-induced lipid peroxidation, and glutathione content in the retina of the rat. One-half hour and four hours after chloroquine administration, increased free activities of lysosomal enzymes and NADPH-induced lipid peroxidation were observed, associated with a decrease in tissue glutathione content. In contrast to the acute effect, chloroquine, given in 7- and 15-day treatment schedules, had no significant effect on the lysosomal enzyme system, while at the same time a normalization or a decrease in NADPH-induced lipid peroxidation, associated with a significant increase in tissue glutathione content, was noted. Catalase and peroxidase activities were decreased after both the acute and the daily treatment schedules. Superoxide dismutase activity, although increased in the high dose acute study, appeared otherwise little affected by chloroquine treatment.
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PMID:Effects of chloroquine on lysosomal enzymes, NADPH-induced lipid peroxidation, and antioxidant enzymes of rat retina. 662 66

Rats were fed diet with or without vitamin A for 5-6 weeks. Vitamin A deficiency had differential effect on the activities of protective enzymes in lung and liver. Superoxide dismutase activity was reduced significantly in lung, whereas remained unchanged in liver, in vitamin A deficient group. Catalase activity was reduced both in lung and liver by inducing vitamin A deficiency. On the other hand, vitamin A deficiency resulted in significant increase in the activity of glutathione peroxidase in lung and had little effect in liver. NADPH dependent lipid peroxidation, as measured by TBA products, remained unaltered, both in lung and liver in vitamin A deficient animals when compared to control group. These results suggest that vitamin A deficiency does not seem to predispose lung and liver to the injurious effects of oxygen toxicity in vivo.
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PMID:Effect of vitamin A deficiency on pulmonary and hepatic protective enzymes in rat. 684 6

Rat liver microsomes catalyzed the oxidative delta 6-desaturation of linoleoyl-CoA (C18: 2, delta 9.12.) to gamma-linolenoyl-CoA (c18: 3, delta 6.9.12.) by using molecular oxygen and NADH or NADPH as the electron donors. The antibodies against cytochrome b5 inhibited markedly the delta 6-desaturation in the intact microsomes of the rat liver, suggesting that cytochrome b5 participated in the delta 6-desaturation. These experimental results led us to the hypothesis that the delta 6-desaturation of linoleoyl-CoA followed the scheme. (See formula in text). Terminal "delta 6-desaturase" was purified from rat liver microsomes for the first time by Triton X-100 solubilization, DEAE-cellulose, CM-Sephadex and cytochrome b5-Sepharose chromatography using its high affinity for cytochrome b5. The final enzyme preparation was homogeneous when applied to sodium dodecyl sulfate disc gel electrophoresis. delta 6-desaturase appeared as a single polypeptide of 66,000 daltons containing 49% nonpolar amino acid residues and one atom of non-heme iron. We confirmed that delta 6-desaturase differed from delta 9-desaturase, which converted stearoyl-CoA to oleoyl-CoA. The delta 6-desaturase activity required NADH (or NADPH), linoleoyl-CoA, oxygen, lipid or detergent and three enzymes, such as NADH-cytochrome b5 reductase (or NADPH-cytochrome P -450 reductase), cytochrome b5, and delta 6-desaturase. The reconstituted system of these components also confirmed the electron flow represented in Scheme 1. The delta 6-desaturase activity was inhibited by iron chelators, cyanine and p-chloromercuriphenyl sulfonate. In the reconstituted system of Km value for linoleoyl-CoA was 47 micro M, the maximal velocity was 83nmol/min/mg protein of delta 6-desaturase and the optimal pH was 7.0. Catalase, superoxide dismutase and t-butanol showed supportive effects on the delta 6-desaturation of the reconstituted system when purified enzymes were employed.
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PMID:[Purification and characterization of Linoleoyl-CoA desaturase from rat liver microsomes (author's transl)]. 726 18

Catalase-bound NADPH both prevents and reverses the accumulation of compound II, an inactive form of catalase that is generated from the normal active intermediate form (compound I) when catalase is exposed to a steady flow of hydrogen peroxide. The mechanism for the regeneration reaction is unknown although NADPH could act either as a one-electron or a two-electron donor. Recently, a reaction scheme has been proposed in which the formation of compound II from compound I generates a neighboring radical species within the protein. NADPH would then donate two electrons, one to compound II for reduction of the iron and the other to the protein free radical. In this paper, we report calculations to find the dominant electron tunneling pathways between NADPH and the heme iron in the catalase from the peroxide-resistant mutant of Proteus mirabilis. Two major tunneling pathways are found which fuse together on Ser-196. It is suggested that the sequence Gly-Ser of the loop that divides the beta 5-strand is the key element for shielding a radical amino acid.
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PMID:Simulations of electron transfer in the NADPH-bound catalase from Proteus mirabilis PR. 754 61

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent tobacco-specific carcinogen, has been demonstrated to induce lung tumors in animals and is suspected to be a human carcinogen. Cytochromes P450 are the major enzymes responsible for the activation of NNK in microsomes from the lung and liver of rat and mouse, as well as human liver. The present study investigated the enzymes responsible for the metabolic activation of NNK in human lung microsomes. In the presence of a NADPH-generating system, the formation of keto aldehyde and keto alcohol (alpha-hydroxylation products, measured together), keto acid, hydroxy acid, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol was observed in human lung microsomes. Carbon monoxide (90%) decreased the rate of NNK oxidation by 5-49%, depending on the human lung microsomal samples analyzed. Coumarin decreased the oxidation of NNK by 9-34%, and an antibody against human P450 2A6 decreased the metabolism of NNK by 8-37%, suggesting the involvement of P450 2A6 in NNK oxidation. alpha-Napthoflavone inhibited NNK oxidation by 6-26%, possibly due to the inhibition of P450 1A1. P450 1A1-expressed microsomes catalyzed the formation of keto aldehyde and keto alcohol, exhibiting Km values of 1400 microM and 371 microM, respectively. In the absence of NADPH, NNK metabolism resulted in the formation of keto acid, keto aldehyde, and keto alcohol, and the activities in different lung samples were decreased by indomethacin (100 microM; cyclooxygenase inhibitor) or nordihydroguaiaretic acid (100 microM; lipoxygenase inhibitor) by 0-27% or 30-66%, respectively. The addition of arachidonic acid (10-100 microM) increased the rate of the formation of keto aldehyde and keto alcohol approximately 2-fold but inhibited the formation of keto acid. Soybean lipoxygenase increased the rate of formation of keto aldehyde and keto alcohol in a concentration-dependent manner. The increased rate in NNK oxidation by arachidonic acid or lipoxygenase was inhibited completely by nordihydroguaiaretic acid. Catalase, thiourea, and conjugated linoleic acid decreased the rate of NNK oxidation by 47, 20, and 45%, respectively. tert-Butyl-hydroperoxide, cumene hydroperoxide, and hydrogen peroxide increased the rate of formation of keto aldehyde and keto alcohol by 210, 40, and 50%, respectively. The results suggest that P450 enzymes are only partially responsible for the activation of NNK in human lung microsomes, and P450 2A6 or a P450 2A6-related enzyme seems to be involved in the activation. Furthermore, lipoxygenase and lipid hydroxperoxides may play important roles in the oxidation of NNK in human lung microsomes.
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PMID:Activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in human lung microsomes by cytochromes P450, lipoxygenase, and hydroperoxides. 758 36

The effects of a low fat diet or diets enriched with either n-6 or n-3 polyunsaturated fatty acids (safflower or fish oil, respectively) on lipid metabolism in periportal and pericentral zones of female rat liver lobules were investigated in relation with cell proliferation after partial hepatectomy. It was found that cell proliferation was localized almost exclusively in periportal and midzonal areas and was significantly reduced by 60% after a fish oil diet only. The fish oil diet caused a strongly increased beta-oxidation capacity in peroxisomes and a moderately increased catalase activity. Catalase activity was mainly localized pericentrally, particularly after partial hepatectomy, whereas the capacity of lipid peroxidation product formation was doubled only in periportal zones in rats on a fish oil diet. The capacity of glucose-6-phosphate dehydrogenase activity to produce NADPH was distinctly lower in both zones of liver lobules as a result of the fish oil diet. Localization patterns and activity in liver lobules of NADPH-cytochrome c (P450) reductase were not significantly affected by fish oil diet. Therefore, it is concluded that elevated peroxisomal beta-oxidation and increased lipid peroxidation capacity in periportal zones of liver lobules coincide with reduced cell proliferation in hepatectomized rats on fish oil diet. These findings support the hypothesis that lipid peroxidation products are involved in the regulation of cell proliferation.
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PMID:Effects of n-3 and n-6 polyunsaturated fatty acid-enriched diets on lipid metabolism in periportal and pericentral compartments of female rat liver lobules and the consequences for cell proliferation after partial hepatectomy. 759 92

NADPH-quinone reductase catalyzes the two-electron reduction of quinones such as menadione, and generally is considered to play a protective role against quinone-mediated toxicity. Recent studies have shown that reactive oxygen intermediates may be produced during metabolism of quinones by quinone reductase. Experiments were carried out to evaluate the effect of iron complexes on production of hydroxyl radical (.OH) when menadione was oxidized by a rat liver cytosolic fraction. Menadione-stimulated H2O2 production when added to the cytosol; dicoumarol, a potent inhibitor of quinone reductase, completely blocked this stimulation. Results were identical with either NADH or NADPH as reductant. In the absence of added iron, .OH, assessed as oxidation of chemical scavengers, was not produced. Various ferric chelates, added to the cytosol in the absence of menadione, did not catalyze .OH production. However, .OH was produced in the presence of menadione with all ferric complexes evaluated except for ferric-desferrioxamine. Catalase, competitive scavengers and GSH inhibited .OH production, as did dicoumarol. Superoxide dismutase inhibited with ferric-ATP, ferric-citrate, ferric-histidine or ferric ammonium sulfate as iron catalysts, but had no effect with ferric-EDTA or ferric-diethylenetriamine penta-acetic acid. Reduction of the ferric complexes was increased by menadione. NADH and NADPH were equally effective as cofactor for all these reactions. Metabolism of menadione in the presence of iron complexes caused inactivation of enzymes present in the cytosolic fraction such as glutamine synthetase and lactic dehydrogenase. These results indicate that metabolism of menadione by quinone reductase can lead to the production of .OH in the presence of various ferric catalysts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Requirement for iron for the production of hydroxyl radicals by rat liver quinone reductase. 769 Apr

Toxicosis due to paraquat, a redox cycling xenobiotic, is still a subject of much debate. In the present study on lipid peroxidation, paraquat had a biphasic effect on the malondialdehyde (MDA) level in rat liver microsomes; stimulation at the initial stage (within 10 min) and depression at the later stage. Although paraquat increased the initial rate of NADPH oxidation dose-dependently, the rate was not necessarily parallel with the increase in the MDA level. The MDA level increased linearly up to 0.1 mM paraquat added, but then it attained a plateau. The stimulation obtained by paraquat within 10 min was absolutely dependent on exogenous Fe2+ ion and NADPH, and the stimulation was entirely SOD sensitive, while the iron-driven increase in MDA was 20% sensitive. Thus, there were different mechanisms between iron-driven lipid peroxidation and paraquat-modified peroxidation. Catalase increased the level, but mannitol, a scavenger of OH, had no effect. EPR spectra showed that superoxide was formed dose-dependently up to 0.1 mM paraquat and that it attained a plateau at the same as MDA level described above. From these results, we concluded that paraquat stimulates lipid peroxidation through a mechanism dependent on the superoxide complex involving Fe2+ ion.
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PMID:Effect of paraquat on the malondialdehyde level in rat liver microsomes (in vitro). 802 66

The rate of generation of reactive oxygen species (ROS) in hepatic microsomes was assayed using a fluorescent probe. This rate was stimulated in a manner proportional to the concentration of NADPH present. NADH could not be substituted for NADPH, and an inhibitor of mixed-function oxidases (SKF 525A) blocked stimulation by NADPH. This suggested the involvement of cytochrome P450 oxidase systems in ROS formation. Low molecular weight iron salts may not have been involved in the stimulated ROS formation since deferoxamine failed to eliminate the oxidative response to NADPH. Catalase only partially inhibited, and glutathione peroxidase did not significantly inhibit this response, implying that hydrogen peroxide does not play a key role. However, since NADPH-enhanced generation of reactive oxygen species was totally prevented by superoxide dismutase, superoxide was an obligatory intermediate. The presence of toluene, ethanol or phenobarbital did not enhance the production of NADPH-effected reactive oxygen species; free radical production was maximal in the absence of substrates subject to oxidation by cytochrome P450 enzymes. Hepatic cytochrome P450 oxidases are likely to contribute significantly to overall ROS formation, even under basal conditions where mixed-function oxidases are not induced.
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PMID:Contribution of hepatic cytochrome P450 systems to the generation of reactive oxygen species. 804 18

NADPH bound to each Catalase subunit was replaced by NADP+ or by the dehydrogenases inhibitor 3-amino-pyridine-adenine dinucleotide phosphate (AADP). The comparison of the three enzyme forms with respect to the capability to dismutate H2O2, or to oxidize ethanol by a peroxidation process using peroxoacetic acid, showed that the enzyme activity is approximately unchanged whatever the nucleotide bound. On the contrary, the dismutation of peroxoacetic acid drops to zero when NADPH is replaced either by the oxidized NADP+ or by the inhibitor AADP. The spectral changes induced by peroxoacetic acid at the heme Soret region indicate that the three enzyme types are quickly oxidized to Compound I [FeV(O)] and successively reduced by two monoelectron intramolecular reactions leading to Compound II [FeIV(OH)] and finally to the resting state (FeIII). Therefore NADPH bound to Catalase is not essential to catalyze peroxidation processes or H2O2 dismutation, but it is essential to prevent the enzyme denaturation and to catalyze dismutation of peroxides other than H2O2.
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PMID:The function of NADPH bound to Catalase. 808 59


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