Catalase (CAT) is an enzyme which promotes the redox reaction

H₂O₂ + H₂R → 2H₂O + R

When R = O₂ it converts hydrogen peroxide to water and molecular oxygen.

Disease relevance of CAT

• A comparison of normal and acatalasemic erythrocytes in the present study indicated that catalase accounts for more than half of the destruction of H2O2 when H2O2 is generated at a rate comparable to that which leads to hemolysis in G6PD- deficient erythrocytes [1].
• Active involvement of catalase during hemolytic crises of favism [2].
• Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival [3].
• To study the effect of catalase on apoptosis induced by DNA-damaging agents, HepG2 cells were infected with adenovirus containing the cDNA of catalase (Ad-Cat) [4].
• Accumulation of excessive ROS, generated through the action of catalase, may lead to oxidative stress, DNA damage, and the development of skin cancer [5].
• Higher erythrocyte catalase activity was found in COPD patients than in healthy controls [6].

Psychiatry related information on CAT

• Antioxidant defense mechanisms of endothelial cells and renal tubular epithelial cells in vitro: role of the glutathione redox cycle and catalase [7].
• No significant differences were observed in erythrocyte glutathione peroxidase, glutathione reductase and catalase activities, between the Rett syndrome patients and the control group [8].
• The activities of superoxide dismutase, catalase and glutathione peroxidase, three enzymes that contribute to the cellular defenses against free radical damage, were measured in different areas of autopsy brains from patients with Alzheimer's disease and from age matched controls [9].
• Catalase, superoxide dismutase and glutathione peroxidase activities of lung and liver during human development [10].
• A patient is reported with del11p13, low catalase level, nephroblastoma, chordee and cryptorchidism, no evident mental retardation, and with normal irides [11].

High impact information on CAT

• The premier discoveries to emanate from my laboratory have been the sulfite oxidase, the several superoxide dismutases, the manganese catalase, and the catalase/peroxidase [12].
• The H2O2-degrading enzyme catalase protects cells from A beta toxicity [13].
• The translocation breakpoint, which identifies the position of the aniridia gene on 11p, is immediately proximal to FSHB, in the interval between FSHB and the catalase gene [14].
• Previous workers observed that while peroxide was clearly responsible for cytolysis of certain antibody-coated tumour cells, extracellular catalase was unable to inhibit this cytolysis, and they suggested that macrophages secrete peroxide into a protected cleft between the phagocyte and target [15].
• Catalase, a scavenger of H2O2, and superoxide dismutase (SOD), a scavenger of O-2, either alone or in combination, did not inhibit NK cell activity [16].

Chemical compound and disease context of CAT

• In contrast, minimal reduction of catalase activity was found, both with and without incubation with aminotriazole, in erythrocytes of a G6PD-deficient boy who had ingested fava beans 7 days earlier and in erythrocytes of seven G6PD-deficient men with a past history of favism [2].
• Adenovirus-mediated overexpression of catalase in the cytosolic or mitochondrial compartment protects against toxicity caused by glutathione depletion in HepG2 cells expressing CYP2E1 [17].
• Adenosine deaminase, 5'-nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in gastric juices from patients with gastric cancer, ulcer, and atrophic gastritis [18].
• The level of thiobarbituric acid-reactive products and the specific activities of catalase and glutathione reductase were significantly higher in muscles from patients with major forms of muscular dystrophies over those of control subjects [19].
• 2. The ratios of glutamate dehydrogenase, glutathione reductase and catalase to lactate dehydrogenase were lower in carcinomas than in normal tissues [20].

Biological context of CAT

• Hyperoxia failed to upregulate endogenous catalase gene expression, in contrast to a marked increase in expression of the heat shock protein gene [21].
• This conclusion was based on the kinetics and dose-response relationships for the effects of azide and cyanide on H2O2 release and on the activities of catalase and myeloperoxidase [22].
• Transfection of human bronchial epithelial cells with fusion genes composed of various lengths of the catalase 5'-flanking region and luciferase as a reporter gene showed low level constitutive promoter activity that did not change after exposure to hyperoxia [21].
• Sequence analysis of 1.7 kb of the 5'-flanking region of the human catalase gene showed features of a "house-keeping" gene (no TATA box, high GC content, multiple CCAAT boxes, and transcription start sites) [21].
• FOXO members have been implicated in cellular protection against oxidative stress via the transcriptional regulation of manganese superoxide dismutase and catalase gene expression [23].

Anatomical context of CAT

• Catalase, azide, and methionine eliminated the inhibitory effect, and catalase and methionine, in fact, enhanced the phagocytic activity of adherent neutrophils [24].
• This enhancement appeared to be due to inhibition of monocyte myeloperoxidase, rather than catalase [22].
• Vulnerability of the human airway epithelium to hyperoxia. Constitutive expression of the catalase gene in human bronchial epithelial cells despite oxidant stress [21].
• Conversely, genetic deficiencies of catalase do not predispose affected erythrocytes to peroxide-induced destruction [1].
• Digitonin titration experiments confirmed the compartmentalized nature of catalase in immature HL-60 cells and were consistent with a cytosolic localization in mature neutrophils [25].

Associations of CAT with chemical compounds

• The viricidal effect was lost when chloride was replaced by sulfate and was inhibited by the peroxidase inhibitor azide and by catalase, but not by heated catalase or superoxide dismutase, implicating H2O2 [26].
• Activity of catalase was further reduced when their red blood cells were incubated with aminotriazole [2].
• Parallel studies using dimethylsulfoxide (DMSO)-induced HL-60 cells and mature neutrophils showed that, in the course of differentiation, there was an apparent shift in the localization of catalase from the granule fraction to the cytosolic fraction [25].
• Since both catalase and the glutathione pathway are dependent on NADPH for function, this finding raises the possibility that both mechanisms destroy H2O2 in human erythrocytes [1].
• These results confirmed earlier studies in vitro indicating that catalase is a major disposer of hydrogen peroxide in human erythrocytes and, like the glutathione peroxidase/reductase pathway, is dependent on the availability of reduced nicotinamide adenine dinucleotide phosphate (NADPH) [2].

Physical interactions of CAT

• Catalase binds Grb2 in tumor cells when stimulated with serum or ligands for integrin receptors [27].
• SHP2 binds catalase and acquires a hydrogen peroxide-resistant phosphatase activity via integrin-signaling [28].
• Recently, however, mammalian catalase was found to have tightly bound NADPH and to require NADPH for the prevention and reversal of inactivation by its toxic substrate (H2O2) [1].
• Amyloid-beta (Abeta) specifically bound purified catalase with high affinity and inhibited catalase breakdown of H(2)O(2) [29].
• Amyloid-beta binds catalase with high affinity and inhibits hydrogen peroxide breakdown [29].

Enzymatic interactions of CAT

• This is the first report that catalase in livers enhances drug oxidation activities catalyzed by P450 in human liver microsomes [30].
• The cytochrome c-catalyzed nitration of tyrosine occurred in proportion to the concentration of hydrogen peroxide, nitrite or cytochrome c. Thecytochromec-catalyzed nitration of tyrosine was inhibited by catalase, sodium azide, cystein, and uric acid [31].

Regulatory relationships of CAT

• However, pulse-chase experiments indicated that p53 protein degradation was enhanced in the catalase-overexpressing cells [4].
• To investigate the relative importance of catalase and the glutathione redox cycle, the experiments were conducted in cells pretreated with amino-triazole (ATZ) to inactivate catalase or with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to inactivate glutathione reductase [32].
• RESULTS: Cu/Zn-SOD, GPx and catalase activities were significantly higher in NAFLD livers than in controls whereas no significant differences were observed in Mn-SOD activity, and thiobarbituric acid-reactive substance (TBARS) concentration [33].
• Moreover, inhibition of catalase blocked the phosphorylation of ERK1/2 but not of p38MAPK in HP100-1 cells [34].
• Antioxidant supplementation enhances the antioxidant enzyme activity of superoxide dismutase and catalase in neutrophils [35].

Other interactions of CAT

• Even at very low H2O2 concentrations GPO reaches only approximately 8% of the rate at which catalase simultaneously degrades H2O2 [36].
• Percoll-sucrose density gradient centrifugation of HL-60 cell cavitates showed a catalase-containing compartment with a mean peak density (1.05 g/mL) significantly lower than that of the major myeloperoxidase-containing compartment (1.08 g/mL); in mature neutrophils, catalase activity comigrated with lactate dehydrogenase (LDH) activity [25].
• No differences in levels of glutathione, catalase, superoxide dismutase, glutathione S-transferase, or glutathione reductase were noted in MCF-GPX-6 cells compared to MCF-7WT cells [37].
• Basal induction was blocked by CYP2E1 inhibitors and catalase [38].
• Control of ceramide-induced apoptosis by IGF-1: involvement of PI-3 kinase, caspase-3 and catalase [39].

Analytical, diagnostic and therapeutic context of CAT

• Ultrastructural localization of catalase by Protein A-gold immunocytochemistry demonstrated four to six catalase-containing compartments in all HL-60 cell profiles [25].
• Differential centrifugation of nitrogen cavitates of HL-60 cells indicated that the putative catalase-containing compartment was relatively fragile compared with the compartment(s) that contained myeloperoxidase (MPO), beta-hexosaminidase, beta-glucuronidase, and lysosomal alpha-mannosidase activities [25].
• The in situ activity of glutathione peroxidase and catalase were not affected by 1,25(OH)2D3, as assessed by the rate of H2O2 degradation by MCF-7 cell cultures [40].
• After treatment with Vp16 or mitomycin C, control cells underwent apoptosis in a p53-dependent manner; however, overexpression of catalase inhibited this apoptosis [4].
• The efficacy of human extracellular-superoxide dismutase type C (EC-SOD C) to limit infarct size after ischemia and reperfusion was explored and compared to that of EC-SOD C combined with catalase (CAT) and to that of CAT alone [41].

References