Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O95477 (membrane-bound)
 29,236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have measured the production of 14CO2 from exogenous [1-14C] phytanic acid in fibroblast monolayers from patients with classical Refsum's disease and peroxisomal disorders. Activities in the different disorders were (percentage of control): classical Refsum's disease (5%), isolated peroxisomal acyl-CoA oxidase deficiency (75%), Zellweger syndrome (4%), neonatal adrenoleukodystrophy (5%), and rhizomelic chondrodysplasia punctate (3%). Absence of complementation was demonstrated between Zellweger syndrome and infantile Refsum's disease lines after polyethylene glycol fusion, with decreases of average activity of 11% relative to unfused cell mixtures. Classical Refsum's disease, rhizomelic chondrodysplasia punctata, and neonatal adrenoleukodystrophy lines all complemented one another, and Zellweger syndrome or infantile Refsum's disease lines, with average activity increases of 522%-772%. No intragenic complementation was observed within either group. Four complementation groups were detected suggesting that at least four genes are involved in phytanic acid alpha-oxidation: one gene for the enzyme phytanic acid alpha-hydroxylase (probably mitochondrial); one gene for a regulatory factor for the expression of phytanic acid alpha-decarboxylation activity and two membrane-bound peroxisomal enzymes involved in the synthesis of plasmalogens; two genes for the assembly of functional peroxisomes and/or import of proteins into peroxisomes.
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PMID:Phytanic acid alpha-oxidation and complementation analysis of classical Refsum and peroxisomal disorders. 246 66

Polarizing material has been reported in the liver of children with infantile Refsum's disease (IRD) and was absent in two patients with the cerebro-hepato-renal syndrome of Zellweger (CHRS). We examined in polarized light 15 liver biopsy and autopsy samples from six other patients with the cerebro-hepato-renal syndrome of Zellweger, two with the rhizomelic form of chondrodysplasia punctata (rCDP) and two with X-linked adrenoleukodystrophy (ALD), all conditions with deficient peroxisomes. Two types of birefringent inclusions were found in CHRS only: the first is transparent in bright field, the second appears as brown granules or rods, similar to lipofuscins. As in IRD large PAS-positive macrophage-like cells contain the transparent type. Electron microscopical investigation of these cells shows trilaminar structures within membrane-bound organelles. The two types were also seen in kidney and brown adipose tissue, the first type in pancreas, the second type in adrenal gland; no such was observed in myocardium or in thyroid gland (CHRS). No birefringent inclusions were present in rCDP and ALD. The nature of the inclusions is still unclear. An accumulation of the transparent polarizing material with increasing age of the patients is most likely.
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PMID:Polarizing inclusions in some organs of children with congenital peroxisomal diseases (Zellweger's, Refsum's, chondrodysplasia punctata (rhizomelic form), X-linked adrenoleukodystrophy). 246 18

The influence of plasmalogen deficiency on membrane lipid mobility was determined by measuring fluorescence anisotropy of trimethylammoniumdiphenylhexatriene (TMA-DPH) and diphenylhexatrienylpropanoylhydrazylstachyose (glyco-DPH) inserted in the plasma membranes of human skin fibroblasts deficient in plasmalogens. The cells used were from patients affected with cerebrohepatorenal (Zellweger) syndrome (CHRS) or rhizomelic chondrodysplasia punctata. Their plasmalogen content (0-5% of total phospholipid) is significantly reduced compared with that of control cells from healthy donors (13-15% of total phospholipid) or of CHRS fibroblasts supplemented with the plasmalogen precursor, hexadecylglycerol. Plasmalogen-deficient cells consistently showed lower fluorescence anisotropies of membrane-bound DPH fluorophores corresponding to higher membrane lipid mobilities as compared to controls. However, very similar lipid mobilities were found for sonicated aqueous dispersions of phospholipids extracted either from CHRS or control cells. Therefore, the differences observed with living cells are not due to differences in the overall physical properties of the membrane lipid constituents. Other phenomena such as lipid asymmetry and/or plasmalogen-protein interactions may be responsible for the effects observed in the biomembranes.
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PMID:Influence of plasmalogen deficiency on membrane fluidity of human skin fibroblasts: a fluorescence anisotropy study. 291 26

In relation to the finding that human skin fibroblasts are capable of de novo either phospholipid biosynthesis, we have studied the properties of acyl-CoA:dihydroxyacetone phosphate acyltransferase in fibroblast homogenates using a new assay method. The results indicate that the acylation of dihydroxyacetone phosphate shows an optimum at pH 5.5 with a broad shoulder of activity up to pH 6.4 and a decline in activity up to pH 8.2. At pH 5.5 the acyltransferase accepts dihydroxyacetone phosphate, but not glycerol 3-phosphate as a substrate. Furthermore, the transferase activity was found to be membrane-bound and inactivated by Triton X-100 at concentrations above 0.025% (w/v). Similar properties have been described for the enzyme as present in rat-liver and guinea-pig liver peroxisomes. These data, together with the finding that acyl-CoA:dihydroxyacetone phosphate acyltransferase is deficient in cultured skin fibroblasts from patients without peroxisomes (Zellweger syndrome), suggest that in cultured skin fibroblasts the enzyme is primarily located in peroxisomes.
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PMID:Acyl-CoA:dihydroxyacetone phosphate acyltransferase in human skin fibroblasts: study of its properties using a new assay method. 353 97

In this paper we show that whereas acyl-CoA: dihydroxyacetone phosphate acyltransferase, a membrane-bound peroxisomal enzyme, is deficient in homogenates of cultured amniotic fluid cells of fetuses with Zellweger syndrome, catalase a soluble peroxisomal matrix enzyme is present in normal amounts. Digitonin titration experiments revealed a striking difference in the percentage of particle-bound catalase in control and Zellweger amniocytes: in Zellweger amniocytes all catalase activity was found to be present in the soluble cytoplasm, (less than 5% particle-bound), whereas in control amniocytes catalase was found to be predominantly particle-bound (62% +/- 8%, n = 5). Measurement of the percentage of particle-bound catalase by means of digitonin titrations thus provides a simple prenatal test for Zellweger syndrome via the direct demonstration of the presence or absence of catalase-containing particles (peroxisomes).
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PMID:A prenatal test for the cerebro-hepato-renal (Zellweger) syndrome by demonstration of the absence of catalase-containing particles (peroxisomes) in cultured amniotic fluid cells. 373 17

Peroxisomes, participants in lipid metabolism, have been shown to be altered in liver in two metabolic diseases in which long-chain fatty acids accumulate in tissues: Zellweger's syndrome and neonatal adrenoleukodystrophy (ALD). The intestine also plays a role in lipid metabolism, and we have had the opportunity to compare peroxisomes in normal intestinal epithelium with those from patients with Zellweger's syndrome and neonatal ALD at the electron microscopic level by using the combined techniques of cytochemistry and stereological analysis. Peroxisomes were numerous in intestinal epithelium of the normal individuals. They were ellipsoidal in shape with average diameters of 0.37 by 0.56 micron and filled with coarsely granular, DAB+ content. Peroxisomes in the intestinal epithelium of the ALD patient were similar in appearance and number but smaller in size (0.28 by 0.44 micron). Peroxisomes of normal appearance were absent from the intestinal epithelium of patients with Zellweger's syndrome; DAB+ content, however, was observed in rare, membrane-bound structures of much smaller size (0.12 by 0.19 micron). In liver of patients with Zellweger's syndrome, peroxisomes are lacking; in neonatal ALD they are abnormal in appearance and greatly reduced in number. The presence of rare minute peroxisomes in the intestinal epithelium in Zellweger's syndrome and of small peroxisomes in this epithelium in neonatal ALD indicate that peroxisomes in the intestinal epithelium are affected in these diseases, but to a lesser extent than in the liver. In the ALD intestinal epithelium, DAB+ material was also seen in long, sinuous, tubular or cisternal elements intermingled and occasionally in continuity with peroxisomes. It is suggested that these represent the early stages of peroxisome formation, the peroxisomal reticulum as originally envisioned by Lazarow, while the rare structures seen in Zellweger's represent rudiments of such a reticulum. Lamellar inclusions and clear spaces occurred in the cytoplasm adjacent to these structures indicating either that material accumulated there had been extracted during fixation or that these regions are more susceptible to autolysis. Mitochondria are also involved in lipid metabolism and have been reported to be abnormal in Zellweger's tissue. No qualitative differences were observed in the mitochondria of the intestinal epithelia examined in this study. Although quantitation revealed a greater mean volume, number, and surface density of mitochondria in the intestinal epithelia of neonatal ALD, it was not a statistically significant difference in all cases.
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PMID:Stereological analysis of peroxisomes and mitochondria in intestinal epithelium of patients with peroxisomal deficiency disorders: Zellweger's syndrome and neonatal-onset adrenoleukodystrophy. 377 84

Activity of acyl-CoA: dihydroxyacetone phosphate acyltransferase, a membrane-bound peroxisomal enzyme in mammalian liver cells catalyzing the first step in the biosynthesis of etherphospholipids, is detectable in thrombocytes isolated from blood of human controls. However, in thrombocytes from patients affected by the cerebro-hepato-renal (Zellweger) syndrome, the activity of this enzyme is severely reduced, permitting rapid postnatal biochemical detection of this severe inborn disease, by measuring the enzyme activity in patients' thrombocytes.
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PMID:Deficiency of acyl-CoA:dihydroxyacetone phosphate acyltransferase in thrombocytes of Zellweger patients: a simple postnatal diagnostic test. 405 81

The activity of peroxisomal enzymes was studied in human liver and cultured human skin fibroblasts in relation to the finding (Goldfischer, S. et al. (1973) Science 182, 62-64) that morphologically distinct peroxisomes are not detectable in patients with the cerebro-hepato-renal (Zellweger) syndrome. In homogenates of liver from the patients, dihydroxyacetone phosphate acyltransferase, a membrane-bound peroxisomal enzyme, is deficient (Schutgens, R.B.H., et al. (1984) Biochem. Biophys. Res. Commun. 120, 179-184). In contrast, there is no deficiency of the soluble peroxisomal matrix enzymes catalase, L-alpha-hydroxyacid oxidase and E-aminoacid oxidase. Catalase is also not deficient in homogenates of cultured skin fibroblasts from the patients. The results of digitonin titration experiments showed that in control fibroblasts at least 70% of the catalase activity is present in subcellular particles distinct from mitochondria or lysosomes. In contrast, all of the catalase activity in fibroblasts from Zellweger patients is found in the same compartment as the cytosolic marker enzyme lactate dehydrogenase.
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PMID:Activity of peroxisomal enzymes and intracellular distribution of catalase in Zellweger syndrome. 614 39

Pipecolic acid is a cyclic secondary imino acid produced in the metabolism of lysine. The metabolic role and fate of pipecolic acid in the human central nervous system are largely unknown. The biochemical defect in two brothers, both less than two years of age, with minor dysmorphic features, progressive neurological dysfunction, and hepatomegaly was identified as hyperpipecolatemia. At autopsy, the older brother's brain weight was increased, with bilateral pallor of the putamen. Distinctive changes included accumulation of 1-1.5 micrometer periodic acid-Schiff (PAS) positive, diastase-resistant, Alcian blue-negative, non-lipid, non-fluorescent granules in astrocytes, satellite cells, and perivascular foot processes. Both light and electron microscopy showed total absence of these granules in neurons. In the older sibling, the liver showed micronodular cirrhosis with distinctive intrahepatocytic accumulation of 0.2-1 micrometer membrane-bound material of low electron density. Pericellular fibrosis and similar cytoplasmic inclusions were present in the liver biopsy from his brother. The distinctive astrocytic storage phenomenon and the liver changes are compared to the findings in Zellweger's syndrome and lysinuric protein intolerance, which are also associated with altered pipecolate metabolism.
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PMID:Pathologic alterations in the brain and liver in hyperpipecolic acidemia. 663 55

Peroxisomes are membrane-bound subcellular organelles that are involved in a variety of cellular functions. Disorders of peroxisomes, either in their assembly or single enzyme deficiencies, manifest themselves in the nervous system both in development and later in life. Most peroxisomal matrix proteins are targeted using one of the targeting sequences, whereas integral peroxisomal membrane proteins employ a different method. Peroxisomal importation is unique, allowing the importation of oligomerized proteins, and uses a specific extended shuttle system of receptor and cargo. The understanding of peroxisomal assembly is important because peroxisomal biogenesis disorders such as Zellweger syndrome result from these defects, and the resulting failure causes widespread deficiencies in peroxisomal biochemical function. X-linked adrenoleukodystrophy, representing the other group of peroxisomal disorders, is caused by the lack of the adrenoleukodystrophy protein, with an accumulation of very long chain fatty acids. New information on clinical incidence, phenotypic variability, and pathogenesis is becoming available and will have implications for possible therapies.
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PMID:Peroxisomal disorders. 1172 89


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