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)

Osteoarthritis was induced in the rabbit by a single intra-articular injection of 0.1 ml of a 1% solution of papain. Degeneration of the cartilage was studied 3 hours, 1, 3 and 8 days after the injection by transmission electron microscopy (TEM) and quantified by measuring the fixed charge density (FCD) and 35S incorporation into glycosaminoglycans. TEM observations of chondrocytes revealed a close correlation between the development of this experimental degenerative joint disease and human osteoarthritis. The administration of CH3-prednisolone (0.1 mg/kg on the 2nd and 5th days, i.a.), of indomethacin (1 mg/kg per day X 7, i.v.), and of catalase (50,000 IU/kg per day X 7, i.m.) modified the biochemical parameters measured 8 days after the papain injection. The corticoid potentiated the action of papain (fall in GAG content and synthesis). None of the non-steroid anti-inflammatory drugs modified the FCD. On the other hand, the increase of 35S incorporation was low after indomethacin and very high after acetylsalicylic acid. Catalase brought about an almost complete recovery of GAG content, together with an important increase in 35S incorporation. This arthropathy could be widely used in experimental pharmacology as a selective test and as a means of studying the mechanism of action of osteoarthritic drugs.
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PMID:Activity of anti-inflammatory drugs on an experimental model of osteoarthritis. 94 94

An inactivation mechanism of active papain (EC 3.4.22.2) by the Cu(2+)-ascorbic acid (AsA) system was examined. Incubation of active papain, which contains an active sulfhydryl (SH) group, with the Cu(2+)-AsA system under aerobic conditions resulted in an irreversible loss of enzyme activity. The enzyme was not inactivated at a molar ratio of enzyme to Cu2+ of 1:< 1, whereas at a molar ratio of 1:1-2, the extent of inactivation showed the same dependence on the extent of oxidation of AsA. Saturation kinetics were observed with respect to the concentration of AsA. The degree of inactivation was dependent on the decrease in SH content of the enzyme. Catalase at a low concentration partially protected the enzyme from inactivation, but did not affect the oxidation of AsA. In addition, catalase at a high concentration completely protected both the enzyme from inactivation and AsA from oxidation. The present results suggest that an additional function of H2O2, besides producing hydroxyl radicals (.OH), is to promote the conversion of Cu+ into Cu2+, and that an active SH group of papain is site-specifically modified by the .OH, resulting in inactivation of the enzyme.
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PMID:On the mechanism of inactivation of active papain by ascorbic acid in the presence of cupric ions. 795 Nov 39

Incubation of papain (EC 3.4.22.2) with ascorbic acid (AsA) and Cu2+ in acetate buffer (pH 5.6) results in an irreversible loss of enzyme activity by site-specific generation of free radicals [H. Kanazawa, S. Fujimoto, A. Ohara, Biol. Pharm.Bull., 16, 11 (1993)]. In this study, the effect of some compounds, known free radical scavengers, on the relationship between the inactivation of papain by the Cu(2+)-AsA system and the oxidation of AsA was investigated. Catalase completely protected the enzyme from inactivation by the Cu(2+)-AsA system, although hydrogen peroxide (H2O2) by itself, known to be generated during the autoxidation of AsA, did not inactivate the enzyme. The oxidation of AsA was unaffected by catalase. Both thiourea and sodium thiocyanate completely protected the enzyme from inactivation, while AsA was partially oxidized only in the initial stage. In the presence of potassium iodide, both the inactivation of the enzyme and the oxidation of AsA were characterized by a rapid initial phase followed by a stable phase where no reaction took place and, subsequently, a slower phase. Histidine partially prevented the inactivation of the enzyme and the oxidation of AsA. The present results suggest that H2O2 serves as a source of secondary, highly reactive species, probably hydroxyl radicals, which are responsible for the inactivation, and that the protection from inactivation by some radical scavengers, such as thiourea, sodium thiocyanate, potassium iodide, and histidine, is based on the removal of metal ions (Cu2+ or Cu+) at the specific site of inactivation.
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PMID:Effect of radical scavengers on the inactivation of papain by ascorbic acid in the presence of cupric ions. 806 51

Scavengers of different active oxygen species affect fibrin plate lysis, catalysed by various proteinases, only at relatively high concentrations (> 10(-2) M). Singlet oxygen scavengers change proteinase activity insignificantly except for strong inhibition of pepsin and papain by sodium azide, but pepsin-by histidine, and fibrinolytic urokinase activity-by all used O2 delta 1 scavengers. Of all used scavengers of OH-radical only ethanol caused significant changes in the proteinases under study, except for alpha-chymotrypsin. The most strong inhibitory effect on proteinase activity was demonstrated by scavengers of superoxide radical. Thus, nitrotetrazolium blue strongly inhibited the activity of plasmin, urokinase (fibrinolytic activity), papain and pepsin. Catalase changed proteinase activity insignificantly, though it leads to total inhibition of pepsin activity at final 4.5 x 10(-4) M concentration. These facts and our previous findings on generating of active oxygen species by proteinases give us grounds to suppose that minor active oxygen species, endogenous for the "proteinase-substrate" system, can participate in the catalytic function of some proteinases.
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PMID:Effect of active oxygen species scavengers on fibrinolytic activity of some proteinases. 874 26

Nitroxide stable free radicals have previously been found to afford protection in various biological systems against diverse types of oxidative stress, including, ischemia/reperfusion, hyperoxia, mechanical trauma, toxic xenobiotics, ionizing radiation, gastric and colonic irritants or strong oxidants. Dismutation of superoxide has originally been suggested to be one of the mechanisms that underlie the anti-oxidant effect of nitroxides. However, no direct evidence has been found, so far, to support this assumption. In the present study, superoxide and H2O2, generated enzymatically, were used to directly inactivate papain, a sulfhydryl enzyme, in vitro. The rate of papain inactivation served to assess the damage. The reaction mixtures contained a chelate in order to prevent the effect of adventitious redox-active metal ions, pre-empt the Fenton reaction and avoid hydroxyl-induced damage. Catalase or SOD alone partially protected the papain from inactivation. The protective effect of nitroxides resembled that of SOD in several aspects: a) nitroxides provided partial protection; b) the protective effect of nitroxides did not increase with the elevation of their concentration (above 0.5 mM); c) the combined addition of SOD and the nitroxide did not provide greater protection than that demonstrated by nitroxides or SOD separately; d) the effects of catalase with the nitroxide were additive; e) the nitroxide, like SOD itself, did not protect papain from H2O2-induced inactivation; f) the nitroxide was found not to be consumed in the course of the reaction but rather to be recycled. The results indicate that: (a) the main species responsible for the papain inactivation in a system in which the effect of transition metals is pre-empted, are O2-. and H2O2; (b) nitroxides inhibit the oxidative damage by removing superoxide not stoichiometrically, but rather catalytically as SOD-mimics; (c) nitroxides do not afford protection when the oxidative damage is induced directly by H2O2 (and not mediated by redox-active metals).
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PMID:An SOD-mimicry mechanism underlies the role of nitroxides in protecting papain from oxidative inactivation. 982 49