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:1.11.1.6 (catalase)
55,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic peroxisomes were studied by morphometric and immunocytochemical techniques in control patients and in four Zellweger syndrome patients, two infantile Refsum's (IRD) patients, one neonatal adrenoleukodystrophy (NALD) patient, and three patients with peroxisomal disorders (PD) which do not fit any currently recognised classification, but have disorders involving a defect in peroxisomal biogenesis. Peroxisomes which were ultrastructurally abnormal and greatly reduced in size and/or number were found in two of the Zellweger syndrome patients, and the NALD and IRD patients. There was variation in their numerical density ranging from none at all in two of the Zellweger syndrome patients to normal numbers in the IRD patients. In most patients there was a decrease in the immunolabelling of catalase over the peroxisomes. In the Zellweger syndrome and NALD patients, the small, abnormal peroxisomes did not label for any of the beta-oxidation proteins. The IRD patients and the PD patients however, were heterogeneous with respect to beta-oxidation labelling. The ultrastructural heterogeneity of peroxisomes in these peroxisomal disorders patients indicates there may be genotypic differences between the major groups and also within each group. The common factor in all the patients in this study where peroxisomes were present was the presence in the hepatic peroxisomes of an electron dense centre which did not label immunocytochemically for catalase or the beta-oxidation enzymes. This electron dense centre may indicate a structural abnormality in the peroxisomes in these patients.
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PMID:Morphometry of peroxisomes and immunolocalization of peroxisomal proteins in the liver of patients with generalised peroxisomal disorders. 750 76

Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum's disease are genetic disorders characterized by the virtual absence of catalase-positive peroxisomes and a general impairment of peroxisomal functions. Recent studies in these three disorders have provided morphologic evidence of peroxisomal "ghosts" of density 1.10 g/cm3 that contain membrane proteins but lack a majority of the matrix enzyme activities. We report here the biochemical studies in a female infant with clinical features of infantile Refsum's disease whose liver and fibroblasts contained cytosolic catalase but no catalase-positive peroxisomes. Oxidation of phytanic and pipecolic acids was severely impaired, whereas oxidation of very-long-chain fatty acids and dihydroxyacetone phosphate acyltransferase activity were only partially decreased. Immunoblot analysis showed that the three peroxisomal beta-oxidation enzymes (acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase) were detectable in liver tissues. The 3-ketoacyl-CoA thiolase was of the mature form (41 kD), in contrast with other peroxisomal disorders with multiple enzyme deficiencies. The majority of these peroxisomal enzyme activities were associated with two subcellular membrane vesicle fractions lacking catalase: one had the density of normal peroxisomes (1.17 g/cm3), the other, yet undescribed, a lower density (1.137 g/cm3). This suggests that peroxisomes (density = 1.17 g/cm3) and structures with lower density (density = 1.137 g/cm3) found in this patient's cultured skin fibroblasts, although lacking catalase, contained functional peroxisomal enzymes. This distinguishes this disorder from other disorders of peroxisome biogenesis.
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PMID:Pseudo infantile Refsum's disease: catalase-deficient peroxisomal particles with partial deficiency of plasmalogen synthesis and oxidation of fatty acids. 751 Aug 68

The clinical distinction between patients with a disorder of peroxisome assembly (e.g., Zellweger syndrome) and those with a defect in a peroxisomal fatty acid beta-oxidation enzyme can be difficult. We studied 29 patients suspected of belonging to the latter group. Using complementation analysis, 24 were found to be deficient in enoylcoenzyme A hydratase/3-hydroxyacylcoenzyme A dehydrogenase bifunctional enzyme and 5 were deficient in acyl-CoA oxidase. Elevated plasma very long-chain fatty acids (VLCFA), impaired fibroblast VLCFA beta-oxidation, decreased fibroblast phytanic acid oxidation, normal plasmalogen synthesis, normal plasma L-pipecolic acid level, and normal subcellular catalase distribution were characteristic findings in both disorders. The elevation in plasma VLCFA levels and impairment in fibroblast VLCFA beta-oxidation were more severe in bifunctional-deficient than in oxidase-deficient patients. The clinical course in bifunctional deficiency (profound hypotonia, neonatal seizures, dysmorphic features, age at death approximately 9 months) was more severe than in oxidase deficiency (moderate hypotonia without dysmorphic features, development of a leukodystrophy, age at death approximately 4 yr). Based on these findings, accurate early diagnosis of these deficiencies of peroxisomal beta-oxidation enzymes is possible.
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PMID:Distinction between peroxisomal bifunctional enzyme and acyl-CoA oxidase deficiencies. 766 38

Results from electron microscopic morphometry, enzyme cytochemistry and immunolocalization in liver biopsies are reviewed. Emphasis is put on the following aspects: 1) relationship between peroxisomal size and enzyme concentration; 2) abnormal enlargement of peroxisomes in many congenital disorders with peroxisomal dysfunction; 3) normal localization of matrix enzymes in several patients with peroxisomal dysfunction, with the exception of catalase, which is mainly cytoplasmic; 4) ghost-like peroxisomes in the liver of several syndromes but not in nine cases labelled as Zellweger; 5) discrepancies between liver and cultured fibroblasts; 6) trilamellar, regularly spaced inclusions, large stacks of which are birefringent, indicate a peroxisomal dysfunction; their absence does not exclude it. The same rule holds for lipid in macrophages which is insoluble in acetone and n-hexane (after fixation). The chemical nature of these two storage materials remains unclear; and 7) proliferation of human peroxisomes is frequent in acquired liver diseases and drug toxicity, but is never accompanied by an increase in size, in contrast to the effect of the fibrates and phthalates in rat and mouse. Novel data from seven peroxisomal patients are included.
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PMID:Human liver pathology in peroxisomal diseases: a review including novel data. 768 91

Peroxisomal-deficient skin fibroblasts from patients with Zellweger's syndrome or infantile Refsum's disease produced fewer prostaglandins than normal skin fibroblasts. Radioimmunoassay indicated a 45-55% decrease in prostaglandin E2 (PGE2) production when Zellweger's fibroblasts were incubated with arachidonic acid. This deficiency was not overcome by pretreatment of the Zellweger's fibroblasts with media containing arachidonic acid, and it was not due to channeling of arachidonic acid into other eicosanoid products. Modifications in the peroxide tone of the Zellweger's fibroblasts by addition of H2O2 or catalase failed to increase PGE2 production. Using Northern analysis, we were unable to detect an mRNA transcript for PGH synthase in unstimulated Zellweger fibroblasts but identified a 4.2-kb mRNA transcript after treatment with phorbol myristate acetate (PMA). Treatment for 6 h with 10 nM PMA raised PGE2 production in normal and Zellweger fibroblasts to equivalent levels. These increases were prevented by addition of H-7, staurosporine, cycloheximide, or actinomycin D. Our findings suggest that the reduced PGE2 production in peroxisomal deficient fibroblasts is due to a decrease in PGH synthase mRNA. The reduction in PGH synthase can be overcome by treatment of the cells with agents which enhance gene expression.
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PMID:Attenuated prostaglandin formation in peroxisomal-deficient human skin fibroblasts. 768 19

An eleven month-old boy presented clinically with craniofacial dysmorphia, severe psychomotor retardation, neurological deterioration, no response to visual and acoustic stimuli, failure to thrive, hepatomegaly and adrenal insufficiency. Specific biochemical markers for a peroxisomal deficiency disorder (Zellweger's syndrome, neonatal adrenoleukodystrophy, infantile Refsum's disease) revealed pathological results for very long chain fatty acids, phytanic acid, pristanic acid, plasmalogen biosynthesis and catalase, thus confirming the clinical diagnosis. Comparison of clinical and biochemical findings in the patient with the characteristics of the three peroxisomal deficiency disorders showed overlapping with each of these disorders, which corresponds to the current view that these three peroxisomal disorders differ only with respect to onset and severity of the clinical manifestations, but not with regard to the biochemical defects.
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PMID:[Zellweger syndrome, neonatal adrenoleukodystrophy or infantile Refsum's disease in a case with generalized peroxisome defect?]. 768 5

PAY genes are required for peroxisome assembly in the yeast Yarrowia lipolytica. Here we show that a mutant strain, pay2, is disrupted for the import of proteins targeted by either peroxisomal targeting signal-1 or -2. Electron microscopy of pay2 cells revealed the presence of small peroxisomal "ghosts," similar to the vesicular structures found in fibroblasts of patients with the human peroxisome assembly disorder, Zellweger syndrome. Functional complementation of pay2 with a plasmid library of Y. lipolytica genomic DNA identified a gene, PAY2, that restores growth of pay2 on oleic acid, import of catalase and multifunctional enzyme into peroxisomes, and formation of wild type peroxisomes. The PAY2 gene encodes Pay2p, a hydrophobic polypeptide of 404 amino acids. An antibody raised against Pay2p recognizes a polypeptide of approximately 42-kDa whose synthesis is induced by growth of Y. lipolytica on oleic acid. Pay2p is a peroxisomal integral membrane protein, as it localizes to carbonate-stripped peroxisomal membranes. Pay2p shows no identity to any known protein. Our results suggest that Pay2p is essential for the activity of the peroxisomal import machinery but does not affect the initial steps of peroxisomal membrane proliferation.
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PMID:The Yarrowia lipolytica gene PAY2 encodes a 42-kDa peroxisomal integral membrane protein essential for matrix protein import and peroxisome enlargement but not for peroxisome membrane proliferation. 783 11

The biogenesis, assembly and import of the peroxisomal enzyme catalase was studied in human skin fibroblasts from control persons and from patients with the Zellweger syndrome. For this purpose, two monoclonal antibodies were generated which are able to discriminate between the monomeric or dimeric form and the tetrameric, enzymically active conformation of the enzyme. Metabolic labelling studies showed that catalase is assembled to the tetrameric conformation within one hour after its synthesis, while it is still in the cytosol of the cell. Subsequently, the enzyme becomes particle-bound in the control cells, a process that is retarded by addition of the catalase inhibitor 3-amino-1,2,4-triazole. However, the tetramer remains in the cytosol in cells from Zellweger patients. It is concluded that newly synthesized catalase can be assembled to a tetramer in the cytosol in human skin fibroblasts. Unfolding of this tetramer prior to import into peroxisomes is indicated.
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PMID:Topology of catalase assembly in human skin fibroblasts. 826 39

Immunohistochemical studies with antisera against four peroxisomal enzymes, catalase and beta-oxidation enzymes (acyl-coenzyme A oxidase, bifunctional protein, and 3-ketoacyl-CoA thiolase), were performed on brain, liver, and kidney specimens from patients with peroxisomal disorders, as well as specimens from three control subjects, by using conventional paraffin-embedded autopsy material. The patients included eight with Zellweger syndrome and one with neonatal adrenoleukodystrophy. In the liver and kidney specimens from all patients, except one with Zellweger syndrome, diffuse immunostaining with all antisera in the cytoplasm of hepatocytes and renal tubular epithelium suggested an absence of peroxisomes but the presence of peroxisomal enzymes. Examination of brain specimens indicated a weak or negative reaction of neurons in the cerebral cortex and a weak reaction of glial cells in the white matter, which suggested maturational delay compared with control subjects. The delayed immunoreactive pattern of peroxisomal enzymes in Zellweger syndrome and neonatal adrenoleukodystrophy may be related to the significant neuropathologic features of polymicrogyria and dysmyelinogenesis. One patient with Zellweger syndrome had a unique finding of a positive granular catalase reaction and a negative reaction with antisera to 3-ketoacyl-coenzyme A thiolase, which suggested a diagnosis of pseudo-Zellweger syndrome. This study validates the application of these immunohistochemical methods to the study of peroxisomal enzymes. Use of these methods improves the accuracy of diagnosis of peroxisomal disorders.
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PMID:Peroxisomal disorders in children: immunohistochemistry and neuropathology. 846 3

We diagnosed a unique peroxisomal disorder in a 32-year-old man with profound mental retardation, mild facial dysmorphism, retinal pigmentary degeneration, seizures, and sensorineural deafness. Although plasma very-long-chain fatty acid profile suggested X-linked adrenoleukodystrophy, marked reduction in fibroblast lignoceric acid oxidation and the presence of cytosolic catalase were consistent with Zellweger syndrome (ZS). Unlike ZS, functional peroxisomes were present as indicated by the density of peroxisomes (1.175 gm/ml) similar to peroxisomes from control cells and by partial deficiencies of fibroblast phytanic acid oxidation and dihydroxyacetone phosphate acyltransferase activity. These findings indicate that this patient has a previously undescribed group 3 peroxisomal disorder (multiple peroxisomal enzyme deficiencies with preserved peroxisomes).
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PMID:Late-onset generalized disorder of peroxisomes. 861 94


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