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)

Mycobacterium phlei contains two catalase activities and a single peroxidase activity. The latter is associated with one of the catalases. The single catalase-peroxidase enzyme accounted for 75% of the total catalase activity and was lost upon acquisition of resistance to the antitubercular drug isoniazid (INH). Heat-treated (68 degrees C) wild-type cells showed similar decreases in catalase activity as well as complete loss of peroxidase activity. Catalase activity in the INH-resistant strain of M. phlei (Inh(r)) was unaffected by heating. The heat-sensitive catalase of the wild-type M. phlei was completely inhibited by 0.1 M INH, and Cu(2+) enhanced this inhibitory effect by 100-fold. No inhibition of activity was found with the heat-stable enzyme. Equivalent inhibition of catalase was also observed with nicotinic acid hydrazide and benzoic acid hydrazide. Peroxidase activity was also completely inhibited by any one of the three hydrazides, either INH, benzoic acid hydrazide, or nicotinic acid hydrazide at 10(-3) M. The presence of two catalase activities and the loss of one (catalase-peroxidase) on acquiring INH resistance or heating wild-type cells was confirmed by acrylamide gel electrophoresis of the cell-free extracts.
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PMID:Differentiation of catalases in Mycobacterium phlei on the basis of susceptibility to isoniazid: association with peroxidase and acquired resistance to isoniazid. 92 Dec 49

As Mycobacterium leprae proliferate inside macrophages, it has been speculated that catalase encoded by katG may protect the bacilli from deleterious effects of peroxide generated from the macrophage and may also play a crucial role in the survival of M. leprae in vivo. However, unlike that of M. tuberculosis, the katG of M. leprae has been reported to be a pseudogene, implicating that isoniazid, which is activated to a potent tuberculocidal agent by catalase, is unlikely to be of therapeutic benefit to leprosy patients. These results raise a question as to how M. leprae avoids H202-mediated killing inside macrophages. To understand the survival of M. leprae in macrophages, the present study attempted to detect catalase-like activity in M. leprae. Catalase-like activity was found in M. leprae cell lysate by the diaminobenzidine (DAB) staining method with non-denaturing polyacrylamide gel electrophoresis. An ammonium sulphate precipitation study revealed that the catalase-like activity was precipitable with 80% ammonium sulphate. The effect of isoniazid (INH) on M. leprae growth was also tested by RT-PCR and radiorespirometric assay to examine catalase-like activity in M. leprae, because INH was activated by catalase. It was found that the viability of M. leprae was decreased at a concentration of 20 microg/ml by radiorespirometric assay and it was inhibited at higher concentrations as determined by RT-PCR. These data suggest that a catalase-like activity other than that encoded by katG is present in M. leprae.
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PMID:Identification of catalase-like activity from Mycobacterium leprae and the relationship between catalase and isonicotinic acid hydrazide (INH). 1147 70

Catalase-peroxidase (KatG) from Mycobacterium tuberculosis, a Class I peroxidase, exhibits high catalase activity and peroxidase activity with various substrates and is responsible for activation of the commonly used antitubercular drug, isoniazid (INH). KatG readily forms amino acid-based radicals during turnover with alkyl peroxides, and this work focuses on extending the identification and characterization of radicals forming on the millisecond to second time scale. Rapid freeze-quench electron paramagnetic resonance spectroscopy (RFQ-EPR) reveals a change in the structure of the initially formed radical in the presence of INH. Heme pocket binding of the drug and knowledge that KatG[Y229F] lacks this signal provides evidence for radical formation on residue Tyr(229). High field RFQ-EPR spectroscopy confirmed a tryptophanyl radical signal, and new analyses of X-band RFQ-EPR spectra also established its presence. High field EPR spectroscopy also confirmed that the majority radical species is a tyrosyl radical. Site-directed mutagenesis, along with simulations of EPR spectra based on x-ray structural data for particular tyrosine and tryptophan residues, enabled assignments based on predicted hyperfine coupling parameters. KatG mutants W107F, Y229F, and the double mutant W107F/Y229F showed alteration in type and yield of radical species. Results are consistent with formation of a tyrosyl radical reasonably assigned to residue Tyr(229) within the first few milliseconds of turnover. This is followed by a mixture of tyrosyl and tryptophanyl radical species and finally to only a tyrosyl radical on residue Tyr(353), which lies more distant from the heme. The radical processing of enzyme lacking the Trp(107)-Tyr(229)-Met(255) adduct (found as a unique structural feature of catalase-peroxidases) is suggested to be a reasonable assignment of the phenomena.
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PMID:Radical sites in Mycobacterium tuberculosis KatG identified using electron paramagnetic resonance spectroscopy, the three-dimensional crystal structure, and electron transfer couplings. 1720 74

Catalase-peroxidases or KatGs from seven different organisms, including Archaeoglobus fulgidus,Bacillus stearothermophilus, Burkholderia pseudomallei, Escherichia coli, Mycobacterium tuberculosis, Rhodobacter capsulatus and Synechocystis PCC 6803, have been characterized to provide a comparative picture of their respective properties. Collectively, the enzymes exhibit similar turnover rates with the catalase and peroxidase reactions varying between 4900 and 15,900s(-1) and 8-25s(-1), respectively. The seven enzymes also exhibited similar pH optima for the peroxidase (4.25-5.0) and catalase reactions (5.75), and high sensitivity to azide and cyanide with IC50 values of 0.2-20muM and 50-170muM, respectively. The K(M)s of the enzymes for H2O2 in the catalase reaction were relatively invariant between 3 and 5mM at pH 7.0, but increased to values ranging from 20 to 225mM at pH 5, consistent with protonation of the distal histidine (pKa approximately 6.2) interfering with H2O2 binding to Cpd I. The catalatic k(cat) was 2- to 3-fold higher at pH 5 compared to pH 7, consistent with the uptake of a proton being involved in the reduction of Cpd I. The turnover rates for the INH lyase and isonicotinoyl-NAD synthase reactions, responsible for the activation of isoniazid as an anti-tubercular drug, were also similar across the seven enzymes, but considerably slower, at 0.5 and 0.002s(-1), respectively. Only the NADH oxidase reaction varied more widely between 10(-4) and 10(-2)s(-1) with the fastest rate being exhibited by the enzyme from B. pseudomallei.
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PMID:Comparative study of catalase-peroxidases (KatGs). 1817 43

KatG (catalase-peroxidase) in Mycobacterium tuberculosis is responsible for activation of isoniazid (INH), a pro-drug used to treat tuberculosis infections. Resistance to INH is a global health problem most often associated with mutations in the katG gene. The origin of INH resistance caused by the KatG[S315G] mutant enzyme is examined here. Overexpressed KatG[S315G] was characterized by optical, EPR, and resonance Raman spectroscopy and by studies of the INH activation mechanism in vitro. Catalase activity and peroxidase activity with artificial substrates were moderately reduced (50 and 35%, respectively), whereas the rates of formation of oxyferryl heme:porphyrin pi-cation radical and the decay of heme intermediates were approximately 2-fold faster in KatG[S315G] compared with WT enzyme. The INH binding affinity for the resting enzyme was unchanged, whereas INH activation, measured by the rate of formation of an acyl-nicotinamide adenine dinucleotide adduct considered to be a bactericidal molecule, was reduced by 30% compared with WT KatG. INH resistance is suggested to arise from a redirection of catalytic intermediates into nonproductive reactions that interfere with oxidation of INH. In the resting mutant enzyme, a rapid evolution of 5-c heme to 6-c species occurred in contrast with the behavior of WT KatG and KatG[S315T] and consistent with greater flexibility at the heme edge in the absence of the hydroxyl of residue 315. Insights into the effects of mutations at residue 315 on enzyme structure, peroxidation kinetics, and specific interactions with INH are presented.
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PMID:Antibiotic resistance in Mycobacterium tuberculosis: peroxidase intermediate bypass causes poor isoniazid activation by the S315G mutant of M. tuberculosis catalase-peroxidase (KatG). 1936 28

Isoniazid (INH) is a first-line antibiotic used in the treatment of infections caused by Mycobacterium tuberculosis. However it has a serious limitation of being hepatotoxic. Delineating the mechanism underlying INH-induced hepatotoxicity may be beneficial in devising ways to counteract its toxic manifestations. Studies in human hepatoma HepG2 cells have indicated that INH exposure causes induction of apoptosis. This study was aimed at identifying the key components/pathways of the INH-induced apoptotic pathway using HepG2 cells. HepG2 cells were exposed to increasing concentrations of INH (6.5, 13, 26, and 52 mM). Hydrogen peroxide (0.3 mM) served as positive control. After incubating for specific time intervals cells were harvested and evidences of cytotoxicity, oxidative stress, and apoptosis were sought. The findings indicated that INH exposure causes increased ROS generation along with alteration in levels of enzymatic antioxidants such as Superoxide dismutase, Catalase, and Glucose-6-Phosphate dehydrogenase. Altered Bcl-2/Bax content, cytochrome-c translocation, caspase activation, and DNA fragmentation emphasized involvement of apoptosis.
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PMID:Isoniazid-induced apoptosis in HepG2 cells: generation of oxidative stress and Bcl-2 down-regulation. 2043 47

Present study deals with the hepatoprotective activity of polyherbal formulation Hepatoplus (HP) as an oral supplement to the INH and RIF induced hepatitis in experimental rats. Rats treated with INH and RIF show abnormal liver function with significant increase in serum transaminases, bilirubin and clotting time (CT) and significant decrease in total protein and Albumin, which is brings to near normal levels by HP and LIV 52 treatments. Rats treated with INH and RIF suffer from oxidative stress in the hepatocytes, due to the decrease in Glutathione (GSH), Glutathione peroxidase (GPX), Catalase (CAT), Super oxide dismutase (SOD) and significant increase in Lipid Per oxidation (LPO). HP decreases the oxidative stress and protects the liver cells membrane from LPO. 85% of DNA damage (comet tail) seen with RIF and INH treatment is reduced to 34.1% on HP application. A decrease of hepatocytes mitochondrial dehydrogenase activity is observed in INH and RIF treatment is restored by HP supplementation. Hepatic apoptotic and CYP2E1 gene expressions were also studied, BAX, p53, Caspase 3 and CYP2E1 were significantly up regulated and Bcl2 was down- regulated in INH and RIF treated rats. Concomitant application of HP prevents the modulation of these gene expressions. It is concluded that high dose of HP (100mg/kg) supplemented along with INH and RIF effectively prevents the toxicity induced by INH and RIF, as effective as 100mg/kg of LIV52.
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PMID:Hepatoprotective activity of hepatoplus on isonaizid and rifampicin induced hepatotoxicity in rats. 2600 6