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)

The intracellular site of synthesis of two peroxisomal enzymes of rat liver, uricase (urate:oxygen oxidoreductase, EC 1.7.3.3) and catalase (hydrogen peroxide:hydrogen peroxide oxidoreductase, EC 1.11.1.6), has been localized on free ribosomes and not membrane-bound ribosomes. Free polysomes and membrane-bound polysomes, prepared by classical cell fractionation techniques from rat liver, were incubated for protein synthesis in a cell-free system derived from rabbit reticulocytes. Characterization of the total translation products by polyacrylamide gel electrophoresis in sodium dodecyl sulfate, as well as by immunoprecipitation with anti-rat albumin anti-serum, confirmed that good separation of the two polysome classes was achieved. Uricase and catalase were immunoprecipitable from translation products directed by free polysomes or phenol-extracted free polysomal mRNA but not from products of membrane-bound polysomes. Furthermore, unlike albumin, nascent uricase and catalase were not cotranslationally segregated by dog pancreas microsomal membranes. The results indicate that uricase and catalase are transferred to the interior of peroxisomes by a post-translational mechanism; an hypothesis is formulated here for the biogenesis of peroxisomes.
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PMID:Biogenesis of peroxisomes: intracellular site of synthesis of catalase and uricase. 36 7

A fully enzymatic method to determine total cholesterol in serum is described. The method appears especially suitable for adaptation to discrete mechanical analyzers either of the single channel or the multi-channel type. The method uses the enzymes cholesterol esterase (EC 3.1.1.13), cholesterol oxidase (EC 1.1.3.6) and peroxidase (EC 1.11.1.7) with 4-aminophenazone and phenol as substrates in the indicator reaction. The method was adapted to the Greiner Selective Analyzer GSA-II. For this purpose the critical parameters of the reaction were intensively examined. The complete reagent is stable within the GSA II dispenser at 4 degrees C for at least 1 week. By omitting cholesterol oxidase in the blank reagent a sample bland and a partial reagent blank are obtained. Within a range up to 10.4 mmol/1 (4.0 g/l) the maximum colour is developed within 6 minutes. The calibration factor was stable for 4 months. The method allows absolute measurements. At concentrations between 2 and 4 mmol/1 within-batch precision ranged from 0.5 to 1.4%. Precision from day to day for the same control sera amounted to 2.8; 2.0; 2.7 and 2.0% for a period of 3 months. Examination of accuracy yielded satisfying results. Ascorbic acid in the physiological range did not alter results to a significant extent. Catalase or novaminesulfone added in vitro did not interfere. Optical interferences by bilirubin, hemoglobin or turbidity are compensated by a sample blank. A comparison of results with the enzymatic method of Roeschlau et al. (Z. Klin. Chem. Klin. Biochem. 12, 226 (1974)) yielded satisfactory agreement. The limits of detection of the present method can be lowered by a factor of 2.2 by replacing phenol by dihalogen phenols.
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PMID:[Enzymatic determination of total cholesterol with the Greiner Selective Analyzer (GSA-II) (author's transl)]. 87 Jun 10

Catalase-bound NADPH both prevents and reverses the accumulation of inactive bovine liver catalase peroxide compound II generated by 'endogenous' donors under conditions of steady H2O2 formation without reacting rapidly with either compound I or compound II. It thus differs both from classical 2-electron donors of the ethanol type, and from 1-electron donors of the ferrocyanide/phenol type. NADPH also inhibits compound II formation induced by the exogenous one-electron donor ferrocyanide. A catalase reaction scheme is proposed in which the initial formation of compound II from compound I involves production of a neighbouring radical species. NADPH blocks the final formation of stable compound II by reacting as a 2-electron donor to compound II and to this free radical. The proposed behaviour resembles that of labile free radicals formed in cytochrome c peroxidase and myoglobin. Such radical migration patterns within haem enzymes are increasingly common motifs.
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PMID:A mechanism for NADPH inhibition of catalase compound II formation. 145 49

Reactivities of benzene metabolites (phenol, catechol, hydroquinone, 1,4-benzoquinone, 1,2,4-benzenetriol) and related polyphenols (resorcinol, pyrogallol, phloroglucinol) with DNA were investigated by a DNA sequencing technique using 32P 5'-end-labeled DNA fragments obtained from human c-Ha-ras-1 protooncogene, and the reaction mechanism was studied by UV-visible and electron-spin resonance spectroscopies. 1,2,4-Benzenetriol caused strong DNA damage even without alkali treatment. Alkali-labile sites induced by 1,2,4-benzenetriol were base residues of guanine and adjacent thymine. Catalase, superoxide dismutase and methional inhibited the DNA damage completely, but sodium formate did not inhibit it. 1,2,4-Benzenetriol-induced DNA damage was inhibited by the addition of a Cu(I)-specific chelating agent, bathocuproine, and was accelerated by the addition of Cu(II). The addition of Fe(III) did not create any significant effects on 1,2,4-benzenetriol-induced DNA damage. Electron-spin resonance studies using spin traps demonstrated that addition of Fe(III) increased hydroxyl radical production during the autoxidation of 1,2,4-benzenetriol, whereas the addition of Cu(II) did not. The results suggest that DNA damage was caused by an unidentified active species which was produced by the autoxidation of 1,2,4-benzenetriol in the presence of Cu(II), rather than by hydroxyl radicals. The possibility that 1,2,4-benzenetriol-induced DNA damage is one of the primary reactions in carcinogenesis induced by benzene is discussed.
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PMID:Human DNA damage induced by 1,2,4-benzenetriol, a benzene metabolite. 290 43

Co(II) ions react with hydrogen peroxide under physiological conditions to form a 'reactive species' that can hydroxylate aromatic compounds (phenol and salicylate) and degrade deoxyribose to thiobarbituric-acid-reactive material. Catalase decreases the formation of this species but superoxide dismutase or low concentrations of ascorbic acid have little effect. EDTA, present in excess over the Co(II), can accelerate deoxyribose degradation and aromatic hydroxylation. In the presence of EDTA, deoxyribose degradation by the reactive species is inhibited competitively by scavengers of the hydroxyl radical (.OH), their effectiveness being related to their second-order rate constants for reaction with .OH. In the absence of EDTA the scavengers inhibit only at much higher concentrations and their order of effectiveness is changed. It is suggested that, in the presence of EDTA, hydroxyl radical is formed 'in free solution' and attacks deoxyribose or an aromatic molecule. In the absence of EDTA, .OH radical is formed in a 'site-specific' manner and is difficult to intercept by .OH scavengers. The relationship of these results to the proposed 'crypto .OH' radical is discussed.
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PMID:Cobalt(II) ion as a promoter of hydroxyl radical and possible 'crypto-hydroxyl' radical formation under physiological conditions. Differential effects of hydroxyl radical scavengers. 299 77

The role of oxygen-derived free radicals (ODFR) in lectin-dependent cellular cytotoxicity (LDCC) in humans was investigated. The hydroxyl radical traps thiourea, methanol, ethanol and phenol were effective in inhibiting LDCC, as was DABCO, a singlet oxygen quencher. The proposed pathway of hydroxyl radical production in living cells is either an iron catalysed Haber-Weiss reaction or a Fenton reaction. The effect of inhibitors of these pathways was investigated. The superoxide anion scavengers superoxide dismutase, ferricytochrome c and Tiron were without effect. It was shown that Tiron inhibits the lucigenin-amplified chemiluminescence produced by the action of xanthine oxidase, and also the lucigenin-amplified chemiluminescence produced by activated PMN, suggesting that this agent (Tiron) scavenges intracellular superoxide anion. Catalase gave slight inhibition of LDCC only. The ferric iron chelator desferrioxamine gave no protection of the target cells, while the ferrous chelator, 1,10-phenanthroline, inhibited LDCC and partially prevented the detection of hydroxyl radicals generated by the Fe2+-H2O2 system. Cibacron blue, an agent that inhibits NAD(P)H linked enzymes, also inhibited LDCC. The cyclo-oxygenase inhibitors indomethacin and salicylate were without effect, while the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) inhibited cytolysis. None of the LDCC inhibitors was cytotoxic to the effector cells or to the target cells, neither did they inhibit lymphocyte-target binding. The findings would suggest that hydroxyl radicals have a role to play in human T-cell mediated cytolysis, either as the active lytic agent or as an epiphenomenon.
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PMID:Hydroxyl radical scavengers inhibit human lectin-dependent cellular cytotoxicity. 301 54

Ferrihemoglobin formation by 4-(dimethylamino)phenol (DMAP), a potent cyanide antidote, is influenced by GSH under formation of various glutathione S-conjugates. Two of these were shown to be still reactive and able to produce ferrihemoglobin. The mechanism of ferrihemoglobin formation is fundamentally different from that found with the parent compound. First of all, induction periods of ferrihemoglobin formation were observed when 4-(dimethylamino)-2-(glutathion-S-yl)-phenol (2-GS-DMAP) and 4-(dimethylamino)-2,6-bis(glutathion-S-yl)phenol (2,6-bis-GS-DMAP) reacted with oxyhemoglobin at 100% and 20% oxygen, but not at 2% oxygen. This behavior points to thioether activation by autoxidation. Autoxidation proceeded in an autocatalytic manner, and the process was markedly modified by reducing agents, e.g., ferrihemoglobin and GSH, and by nucleophiles like GSH. Superoxide dismutase extended the lag phase of autoxidation and ferrihemoglobin formation. Catalase diminished markedly ferrihemoglobin formation, particularly at low oxygen pressure. The extent of this effect was much higher than expected if H2O2 had formed ferrihemoglobin directly. Conceivably, H2O2 might react with the thioethers or their oxidation products to give hitherto unidentified compounds of high catalytic activity in ferrihemoglobin formation. The results indicate that ferrihemoglobin formation by reactive glutathione conjugates of DMAP is essentially not a co-oxidation process as found with the parent DMAP and other aminophenols, but is mainly caused by an autocatalytic autoxidation process with formation of various reactive intermediates including superoxide radical anions and hydrogen peroxide. It appears that glutathione conjugation of autoxidizable aromatics does not necessarily lead to inactive phase II metabolites but opens new avenues of toxication reactions that may be a broader toxicological significance.
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PMID:Reactivity of glutathione adducts of 4-(dimethylamino)phenol. Involvement of reactive oxygen species during the interaction with oxyhemoglobin. 757 22

The purpose of this study was to gain direct insights into mechanisms by which myoglobin induces proximal tubular cell death. To avoid confounding systemic and hemodynamic influences, an in vitro model of myoglobin cytotoxicity was employed. Human proximal tubular (HK-2) cells were incubated with 10 mg/ml myoglobin, and after 24 hours the lethal cell injury was assessed (vital dye uptake; LDH release). The roles played by heme oxygenase (HO), cytochrome p450, free iron, intracellular Ca2+, nitric oxide, H2O2, hydroxyl radical (-OH), and mitochondrial electron transport were assessed. HO inhibition (Sn protoporphyrin) conferred almost complete protection against myoglobin cytotoxicity (92% vs. 22% cell viability). This benefit was fully reproduced by iron chelation therapy (deferoxamine). Conversely, divergent cytochrome p450 inhibitors (cimetidine, aminobenzotriazole, troleandomycin) were without effect Catalase induced dose dependent cytoprotection, virtually complete, at a 5000 U/ml dose. Conversely, -OH scavengers (benzoate, DMTU, mannitol), xanthine oxidase inhibition (oxypurinol), superoxide dismutase, and manipulators of nitric oxide expression (L-NAME, L-arginine) were without effect. Intracellular (but not extracellular) calcium chelation (BAPTA-AM) caused approximately 50% reductions in myoglobin-induced cell death. The ability of Ca2+ (plus iron) to drive H2O2 production (phenol red assay) suggests one potential mechanism. Blockade of site 2 (antimycin) and site 3 (azide), but not site 1 (rotenone), mitochondrial electron transport significantly reduced myoglobin cytotoxicity. Inhibition of Na, K-ATPase driven respiration (ouabain) produced a similar protective effect. We conclude that: (1) HO-generated iron release initiates myoglobin toxicity in HK-2 cells; (2) myoglobin, rather than cytochrome p450, appears to be the more likely source of toxic iron release; (3) H2O2 generation, perhaps facilitated by intracellular Ca2+/iron, appears to play a critical role; and (4) cellular respiration/terminal mitochondrial electron transport ultimately helps mediate myoglobin's cytotoxic effect. Formation of poorly characterized toxic iron/H2O2-based reactive intermediates at this site seems likely to be involved.
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PMID:Myoglobin toxicity in proximal human kidney cells: roles of Fe, Ca2+, H2O2, and terminal mitochondrial electron transport. 906 5

Increased production of reactive oxygen metabolites (ROM) can contribute to the initiation phase of nephrotoxic and ischemic acute renal failure (ARF). However, whether altered ROM expression also exists during the maintenance phase of ARF has not been adequately assessed. Since diverse forms of tubular injury can initiate a "cytoresistant state," this study tested whether a down-regulation of ROM expression might develop in the aftermath of acute tubular damage, potentially limiting renal susceptibility to further attack. To test this hypothesis, rats were subjected to either mild myohemoglobinuria (glycerol injection) or bilateral ureteral obstruction and 24 hours later, cytoresistant proximal tubular segments (PTS) were isolated to assess ROM expression. PTS from sham operated rats were used to establish normal values. Both sets of cytoresistant PTS manifested approximately 75% reductions in H2O2 levels, as assessed by the phenol red/horseradish peroxidase technique (P < 0.01 to 0.001). A 40% reduction in hydroxyl radical (.OH) levels was also observed (salicylate trap method), thereby substantiating decreased oxidant stress in cytoresistant PTS. Catalase, glutathione peroxidase, and free iron levels were comparable in control and cytoresistant PTS, suggesting that decreased H2O2 production (such as by mitochondria) was the cause of the decreased oxidant stress. To test this latter hypothesis, H2O2 expression by control and cytoresistant PTS was assessed in the presence of respiratory chain inhibitors. Although site 1 and site 3 inhibition markedly suppressed H2O2 production in control PTS, they had no impact on H2O2 production in cytoresistant PTS, implying that production at these sites was already maximally suppressed. Correlates of the decreased mitochondrial H2O2 production were improvements in cell energetics (increased ATP/ADP ratios with Na ionophore treatment) and approximately 40 to 90% increases in PTS/renal cortical glutathione content. We conclude that: (1) proximal tubule H2O2/.OH expression can be downregulated during the maintenance phase of ARF; (2) this seemingly reflects a decrease in mitochondrial ROM generation; and (3) the associated improvements in glutathione content and/or cellular energetics could conceivably contribute to a post-injury cytoresistant state.
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PMID:Decreased expression of mitochondrial-derived H2O2 and hydroxyl radical in cytoresistant proximal tubules. 932 33

Catalase catalyzed the peroxynitrite-mediated nitration of 4-hydroxyphenylacetic acid. The curve for the pH dependence of nitration was similar to that for the reaction between peroxynitrite and phenol. Cyanide, azide, and 3-amino-1,2,4-triazole inhibited the nitration in a dose-dependent way. When catalase was mixed with peroxynitrite, Compound I was detected as an intermediate. Because azide was an electron donor for the peroxidatic action of catalase, and because 3-amino-1,2,4-triazole inhibited catalase activity by binding with Compound I, peroxynitrite-mediated phenolic nitration was probably accompanied by Compound I formation. Both catalase and superoxide dismutase protected Escherichia coli from peroxynitrite toxicity.
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PMID:Catalase catalyzes of peroxynitrite-mediated phenolic nitration. 957 74


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