Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variety of prostaglandin synthetase inhibitors are cooxygenated during arachidonic acid peroxidation catalyzed by rat renal medulla prostaglandin synthetase or soybean lipoxygenase. Phenylbutazone, aminopyrine, 1,3-diphenylisobenzofuran, paracetamol, p-aminophenol, p-phenetidine and other o- and m-substituted aminophenol derivatives were cooxygenated, whereby prostaglandin synthetase inhibition was significantly weakened due to the formation of less inhibitory metabolites. In contrast, the inhibitory potency of diclofenac, indomethacin and phenacetin and its analogues remained unchanged during prostaglandin synthesis inhibition, because these compounds were no suitable cooxygenation substrates. Evidence is given that quinone imines may not be involved in the cooxidative metabolism of paracetamol and other aminophenols. As to the mechanisms of cooxygenation of suitable substrates dependent on their chemical structures either the arachidonic acid oxygenase or the subsequent hydroperoxidase reaction may trigger the oxygenation. 1,3-Diphenylisobenzofuran is metabolized during the formation of arachidonic acid hydroperoxides in contrast to paracetamol, which requires an additional peroxidase reaction to yield reactive metabolites.
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PMID:Decreasing inhibitory potency of prostaglandin synthetase inhibitors during their cooxidative metabolism. Studies on aminophenols, pyrazolon derivatives and 1,3-diphenylisobenzofuran. 641 40

There has been no cogent hypothesis to explain the molecular basis of analgesic and non-steroidal anti-inflammatory drug (NSAID) associated renal papillary necrosis (RPN) and upper urothelial carcinoma (UUC). The microsomal cytochrome P-450 enzyme system may generate reactive intermediates which promote pathophysiological effects in the lung, liver and renal cortex, but the absence of P-450 activity in the medulla suggests that it is unlikely that similar events lead to RPN and UUC. Other enzymes (eg. peroxidases) convert substituted aromatics into benzoquinoneimines (an intermediate that has previously been defined in P-450-mediated toxicity). The medulla is rich in fatty acid peroxidases involved in the metabolism of arachidonic acid. NSAID and analgesics interact with key enzymes in this pathway, which could lead to the co-oxygenation of exogenous and endogenous compounds via the peroxidase, lipoxygenase, or prostaglandin hydroperoxidase enzymes. The generation of reactive molecules in the medulla could explain both RPN and UUC via the alkylation of macromolecules. The formation of free radicals would give rise to extensive lipid peroxidation, (there are large quantities of free polyunsaturated fatty acids in the medullary interstitial cells), an event of major potential importance to local cell destruction and genotoxic effects. At present this proposed mechanism of co-oxygenation offers the most attractive working hypothesis to explain the molecular pathogenesis of both RPN and UUC.
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PMID:The role of metabolic activation of analgesics and non-steroidal anti-inflammatory drugs in the development of renal papillary necrosis and upper urothelial carcinoma. 643 33

A low Se intake in dietetically treated patients with phenylketonuria (PKU) or maple syrup urine disease (MSUD) leads to a marked reduction of the platelet glutathione peroxidase activity (GSHPx). The mean value amounted to 2.0 U/10(11) platelets with t-butyl hydroperoxidase (t-BOOH) (2.2 U/10(11) with H2O2) in patients and 5.8 U/10(11) with t-BOOH (5.4 U/10(11) with H2O2) in the control children. After Se supplementation with yeast rich in Se (dose: 135 micrograms Se/m2) the GSHPx activities rapidly increased. They reached a plateau after 2-3 weeks and remained there during the following 15-20 weeks of supplementation. After the cessation of supplementation there was a slow decrease, the values reached a low plateau after 24 weeks. In addition platelet glutathione S-transferase (GSHTf) was estimated with 1-chloro-2,4-dinitrobenzene. No significant difference between the values in healthy and dietetically treated patients in a low or normal Se state was observed. GSHTf did not exhibit peroxidase activity and did not show a compensatory increase when Se dependent GSHPx activity was low. The patients do not reveal clinical signs of disturbed platelet function. GSHPx may act in platelets via lipoxygenase on the prostaglandin pathway. The physiologic consequence of altered arachidonate metabolism, when GSHPx is deficient in platelets, remains to be elucidated.
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PMID:Glutathione peroxidase and glutathione S-transferase activity of platelets. 662 46

This article gives a synopsis of the inflammatory reactions as well as its mediators under special consideration of the efferent part of the reaction. There is no doubt that histamine, complement, and the kinin system play an essential role; arachidonic acid (eicosatetraenic acid) and its metabolites, however, have gained comparable significance: prostaglandines, prostacyclines, and thromboxanes as metabolites of the cyclo-oxygenase, the leucotrienes SRS-A (slow reacting substances of anaphylaxis) and ECF (eosinophilic chemotactic factor) mediated via lipoxygenase. Moreover, oxygen and its metabolites hydrogen peroxide (H2O2), peroxide radicals (O-2), and hydroxyl radicals (.OH) as well as activated oxygen (singulett oxygen (1O2) play an important part with all aerobic living organisms. Inborn enzyme deficiency of the oxygen metabolism such as NADPH oxidase or cytochrome b-245 deficiency lead to chronic septic granulomatosis. The disease is characterized by reduced resistence against infections, decreased phagocytosis, insufficient killing of bacteria by leucocytes, and diminished oxygen burst. Thus the underlying enzyme deficiency leads to reduced formation of peroxide radicals frequently causing infections with septic complications. On the other hand, increased formation or reduced degradation of peroxide radicals may result in pathological reactions like chromosomal alterations, lipidperoxidation or oxidation of sulph-hydryl groups. The fact that increased peroxide radical formation may cause inflammation or chromosomal aberration is of importance with regard to the pathogenesis of several chronic inflammatory diseases of unknown etiology, such as systemic scleroderma or lupus erythematodes. The enzyme superoxide dismutase (SOD) converts peroxide radicals (O-2) into hydrogen peroxide (H2O2) which can be inactivated by catalase or peroxidase. Consequently, treatment with SOD may have an effective influence on chronic inflammatory dermatoses of unknown pathogenesis.
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PMID:[Biochemical aspects of the inflammatory reaction - with special reference to oxygen]. 666 95

The enzymes of arachidonate metabolism via the lipoxygenase pathway in human platelet cytosol have been characterized and partially purified. The lipoxygenase activity has a pH optimum of 7.3 and reaches half-maximal activity at an arachidonate concentration of 80 microM. The oxidation of arachidonate by these enzymes is inhibited by reagents that modify sulfhydryl groups. Two separable lipoxygenase activities can be detected by chromatography of platelet cytosol on Sephadex G-150 and of partially purified preparations on DEAE-Sephadex. One of these has an apparent Mr of 100,000. A second enzyme species behaves as a Mr 160,000 entity containing, in addition to lipoxygenase, a peroxidase activity that catalyzes the conversion of 12L-hydroperoxy-5,8,10,14-icosatetraenoic acid (HPETE) to 12L-hydroxy-5,8,10,14-icosatetraenoic acid (HETE). Aspirin, indomethacin, sodium salicylate, phenylbutazone, ibuprofen, naproxen, and sulindac, but not acetaminophen or phenacetin, give rise to increased levels of HPETE in the lipoxygenase pathway. This increase in HPETE levels is the result of the ability of these drugs to inhibit directly the enzymatic conversion of HPETE to HETE.
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PMID:Arachidonate metabolism via lipoxygenase and 12L-hydroperoxy-5,8,10,14-icosatetraenoic acid peroxidase sensitive to anti-inflammatory drugs. 676 37

Arachidonic acid is converted into several more polar products in addition to 12-l-hydroperoxyeicosa-5,8,10,14-tetraenoic acid (12-HPETE) and 12-l-hydroxyeicosa-5,8,10,14-tetraenoic acid (12-HETE) by the cytosol fractions of rat platelets. The more polar products are formed via the lipoxygenase pathways in the same way as are 12-HPETE and 12-HETE, since their formation is not inhibited by indomethacin but by eicosa-5,8,11,14-tetraynoic acid (ETYA). The presence of 0.5-1.5mm-reduced glutathione (GSH) in the reaction mixture prevents the formation of the more polar products and produces 12-HETE as the only metabolite from arachidonic acid by the 12-lipoxygenase pathway. l-Cysteine has the same effect as GSH. However, oxidized glutathione (GSSG) and l-cystine are not able to prevent the formation of the more polar products. The results indicate that 12-HPETE peroxidase in the 12-lipoxygenase pathway is a GSH-dependent peroxidase and the more polar products might be formed from the non-enzymic breakdown of the primary 12-lipoxygenase product of 12-HPETE, owing to insufficient capability of the subsequent peroxidase system to completely reduce 12-HPETE to 12-HETE. Thus the presence of GSH in the reaction mixture offers a convenient and precise cell-free assay system for 12-lipoxygenase in rat platelets. Routine assays of 12-lipoxygenase are carried out in the presence of 1mm-GSH in the reaction mixture. The synthesis of 12-HETE by 12-lipoxygenase is linear during the first 4 min of incubation at 37 degrees C, and has a pH optimum of 7.7. The 12-lipoxygenase reaches half-maximal activity at an arachidonate concentration of 20mum. Fractionation of cell homogenates indicates that the cytosol fraction possesses almost all the 12-lipoxygenase activity, whereas the microsomal fraction exhibits little enzyme activity.
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PMID:Effects of reduced glutathione on the 12-lipoxygenase pathways in rat platelets. 680 97

Dielectric heating at frequencies of 42 and 2450 MHz was applied to whole soybeans of natural moisture content for varies exposure times. The minimum energy absorbed (MEA) was calculated from moisture-loss and temperature-elevation data. Biochemical analyses were performed to determine protein dispersibility index (PDI), nitrogen solubility index (NSI), and trypsin-inhibitor, urease, lipoxygenase, and peroxidase activities. Because the heating rates were different at the two frequencies for the power levels used, plots of the biochemical properties against temperature of exposure time showed an apparent frequency dependence. This dependence on frequency disappeared, however, when MEA was substituted as the independent variable. Chemical analyses revealed that dielectric heating of soybeans at natural moisture levels should be as effective as conventional steam toasting in reducing trypsin-inhibitor activity. PDI and NSI, but not urease, were suitable indicators of trypsin-inhibitor inactivation by dielectric heating. Lipoxygenase was completely inactivated by the dielectric-heating treatments that gave suitable trypsin-inhibitor inactivation, but peroxidase activity remained relatively high, offering possible advantages for bleaching and improved soy product color.
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PMID:Effects of 42- and 2450-MHz dielectric heating on nutrition-related properties of soybeans. 692 Apr 15

Lipid peroxides are produced during the enzymatic conversion of arachidonic acid to prostaglandins, thromboxane, prostacyclin, and leukotrienes. These peroxides include hydroperoxides of arachidonic acid formed by lipoxygenase and the prostaglandin endoperoxide intermediates produced by action of prostaglandin endoperoxide synthetase. A number of steps in the arachidonate-dependent prostaglandin pathway are vulnerable to antioxidant affects. Such points in the biosynthetic sequence include prostaglandin endoperoxide synthetase, both the cyclooxygenase and peroxidase activity, prostacyclin synthetase, thromboxane synthetase, and lipooxygenase. Antioxidants added in vitro have been shown to affect prostaglandin synthesis. The present review will stress the limited information concerning the in vivo effect of antioxidants. Studies carried out in the investigator's laboratory on prostaglandin synthesis have utilized rats deficient or replete in vitamin E or propyl gallate (an antioxidant). Differentiation of germ cells in the testis of the male rat is arrested in vitamin E deficiency. Testis microsomal prostaglandin synthesis is altered prior to any overt morphological change. The effect of exogenous antioxidant in either rat testis or mammary gland preparation depends both on the type of antioxidant and the concentration. However, the effects of in vivo and in vitro antioxidant on arachidonate turnover are not identical. The physiological effect of antioxidants on prostaglandin synthesis appear to be specific.
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PMID:Antioxidant effects on the prostaglandin endoperoxide synthetase product profile. 746 Nov 42

The pyrrolizinyl substituted acrylic acid derivatives represent another class of dual and selective inhibitors of cyclooxygenase and 5-lipoxygenase. By modifying their substitution pattern at the phenyl moiety of C-6 the balance between the activity against cyclooxygenase and against 5-lipoxygenase can be shifted. Structure-activity relationships are discussed. Compound 6k is the most potent and well-balanced dual inhibitor of both enzymes, while the highest selectivity of lipoxygenase inhibition was found for 6j. The activity and selectivity of compounds with an additional sulfur moiety depend on the oxidation status of this atom, giving an indication of the discussed coupling between peroxidase and cyclooxygenase. The inhibition of cyclooxygenase was determined in a bovine thrombocyte intact cell assay and that of 5-lipoxygenase using intact bovine PMNLs.
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PMID:Non-steroidal anti-inflammatory agents, Part 19. E-2-pyrrolizin-5-yl acrylic acids as potent dual or selective inhibitors of bovine cyclooxygenase and 5-lipoxygenase. 748 26

Human LDLs oxidized with Cu2+ are known to promote leukocyte-endothelial cell adhesion (LECA) and albumin leakage in postcapillary venules. The objective of this study was to compare the ability of LDL oxidized with Cu2+ (Cu-LDL), phospholipase A2 plus lipoxygenase (PLA2-LDL), horseradish peroxidase plus H2O2 (HRP-LDL), or -OCl (-OCl-LDL) to promote (1)neutrophil-endothelial cell adhesion (NECA) in vitro and (2)LECA and albumin leakage in rat mesenteric venules. In vitro adhesion assays revealed that only Cu-LDL elicited a dose-dependent NECA response, whereas PLA2-LDL but not normal (N-LDL), HRP-LDL, or -OCl-LDL increased NECA at the highest concentration studied (670 micrograms/mL). The magnitude of the NECA responses elicited by the different forms of oxidized LDL was related to the degree of lipid peroxidation but unrelated to the level of protein oxidation. Local intra-arterial infusion of Cu-LDL, PLA2-LDL, or -OCl-LDL but not N-LDL elicited significant increases in leukocyte adherence and emigration, mast cell degranulation, and albumin leakage in rat mesenteric venules. The LECA induced by all forms of oxidized LDL was not accompanied by significant alterations of venular shear rate.
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PMID:Oxidized LDL-induced microvascular dysfunction. Dependence on oxidation procedure. 748 57


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