Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.1.18 (branching enzyme)
 628 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A baby girl was born hypotonic and was respirator-dependent until death at 43 days of age. A muscle biopsy revealed PAS-positive, diastase-resistant sarcoplasmic inclusions with a vaguely fibrillar structure by electron microscopy. Biochemical studies at autopsy disclosed complete absence of branching enzyme in skeletal muscle and heart, and a deficiency of phosphorylase activity in skeletal muscle with a modest reduction in myocardium. Storage material was present in glia and perikarya of neurons, increasing in amount in the rostrocaudal direction, involving most severely the motor neurons in the brain stem and spinal cord, dorsal root ganglia and myenteric plexi. Inclusions were also present in most organs, especially liver and skeletal muscle. Ultrastructurally, the inclusions ranged from granular aggregates of membrane-bound material concentrated in the region of Golgi apparatus to large filamentous bodies similar to polyglucosan bodies. This baby differs from other patients with infantile glycogenosis IV by the severity and onset of symptoms at birth, involvement of neuronal perikarya and widespread extraneural deposits. The combined deficiencies of branching enzyme and phosphorylase may have accounted for the unique clinical and neuropathological findings.
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PMID:Concomitant branching enzyme and phosphorylase deficiencies. An unusual glycogenosis with extensive neuronal polyglucosan storage. 817 7

Glycogen storage disease type IV (GSD-IV) is a rare autosomal recessive disease caused by a deficiency of glycogen branching enzyme (GBE) activity. This results in the accumulation of abnormal glycogen in the liver and other organs. We report the case of a 14-month-old female patient with typical hepatic pathologic findings of GSD-IV. The patient suffered from decreased muscle tone and progressive hepatosplenomegaly since birth. A wedge biopsy of the liver showed enlarged hepatocytes with colorless to faintly eosinophilic ground glass intracytoplasmic inclusions. Portal fibrosis and lobular, fibrous septa were present. Ultrastructure of the inclusions revealed non-membrane-bound fibrillar material 5 nm in maximal diameter. Enzyme study revealed a total deficiency of GBE activity.
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PMID:Glycogen storage disease type IV: a case report. 1053 7

The molecular mechanisms regulating hemicelluloses and pectin biosynthesis are poorly understood. An important question in this regard is how glycosyltransferases are oriented in the Golgi cisternae, and how nucleotide sugars are made available for the synthesis of the polymers. Here we show that the branching enzyme xyloglucan alpha,1-2 fucosyltransferase (XG-FucTase) from growing pea (Pisum sativum) epicotyls was latent and protected against proteolytic inactivation on intact, right-side-in pea stem Golgi vesicles. Moreover, much of the XG-FucTase activity was membrane associated. These data indicate that XG-FucTase is a membrane-bound luminal enzyme. GDP-Fuc uptake studies demonstrated that GDP-Fuc was taken up into Golgi vesicles in a protein-mediated process, and that this uptake was not competed by UDP-Glc, suggesting that a specific GDP-Fuc transporter is involved in xyloglucan biosynthesis. Once in the lumen, Fuc was transferred onto endogenous acceptors, including xyloglucan. GDPase activity was detected in the lumen of the vesicles, suggesting than the GDP produced upon transfer of Fuc was hydrolyzed to GMP and inorganic phosphate. We suggest than the GDP-Fuc transporter and GDPase may be regulators of xyloglucan fucosylation in the Golgi apparatus from pea epicotyls.
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PMID:GDP-fucose uptake into the Golgi apparatus during xyloglucan biosynthesis requires the activity of a transporter-like protein other than the UDP-glucose transporter. 1071 51

A diagnosis of GSD-IV was established in three premature, floppy infants based on characteristic, however unusually pleomorphic polyglucosan bodies at the electron microscopic level, glycogen branching enzyme deficiency in two cases, and the identification of GBE1 mutations in two cases. Pleomorphic polyglucosan bodies in muscle fibers and macrophages, and less severe in Schwann cells and microglial cells were noted. Most of the inclusions were granular and membrane-bound; others had an irregular contour, were more electron dense and were not membrane bound, or homogenous ('hyaline'). A paracrystalline pattern of granules was repeatedly noted showing a periodicity of about 10 nm with an angle of about 60 degrees or 120 degrees at sites of changing linear orientation. Malteser crosses were noted under polarized light in the larger inclusions. Some inclusions were PAS positive and others were not. Severely atrophic muscle fibers without inclusions, but with depletion of myofibrils in the plane of section studied indicated the devastating myopathic nature of the disease. Schwann cells and peripheral axons were less severely affected as was the spinal cord. Two novel protein-truncating mutations (c.1077insT, p.V359fsX16; g.101517_127067del25550insCAGTACTAA, DelExon4-7) were identified in these families. The present findings extend previous studies indicating that truncating GBE1 mutations cause a spectrum of severe diseases ranging from generalized intrauterine hydrops to fatal perinatal hypotonia and fatal cardiomyopathy in the first months of life.
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PMID:Congenital type IV glycogenosis: the spectrum of pleomorphic polyglucosan bodies in muscle, nerve, and spinal cord with two novel mutations in the GBE1 gene. 1866 Nov 38

Glycogenosis type IV is caused by a deficiency of glycogen branching enzyme (alpha-1,4 glucan 6-transglucosylase). Adult polyglucosan body disease (APBD) may represent a neuropathological hallmark of the adult form of this storage disease of the central nervous system. We analysed a case of a 45-year-old unconscious woman who died three days after admission to the hospital. Neuropathological examination revealed massive accumulation of polyglucosan bodies (PBs) in the cortex and white matter of the whole brain. PBs were located in the processes of neurons, astrocytes and microglial cells. The storage material in the cytoplasm of neurons and glial cells was visible as fine granules. Ultrastructurally, PBs consisted of non-membrane-bound deposits of branched and densely packed filaments, measuring about 7-10 nm in diameter, typical of polyglucosan bodies. APBD patients develop upper and lower neuron disease and dementia, probably secondary to the disruption of neuron and astrocyte functions.
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PMID:Immunohistochemical and ultrastructural changes in the brain in probable adult glycogenosis type IV: adult polyglucosan body disease. 1882 92

Signal peptide peptidase-like 3 (Sppl3) is a Golgi-resident intramembrane-cleaving protease that is highly conserved among multicellular eukaryotes pointing to pivotal physiological functions in the Golgi network which are only beginning to emerge. Recently, Sppl3 was shown to control protein N-glycosylation, when the key branching enzyme N-acetylglucosaminyltransferase V (GnT-V) and other medial/trans Golgi glycosyltransferases were identified as first physiological Sppl3 substrates. Sppl3-mediated endoproteolysis releases the catalytic ectodomains of these enzymes from their type II membrane anchors. Protein glycosylation is a multistep process involving numerous type II membrane-bound enzymes, but it remains unclear whether only few of them are Sppl3 substrates or whether Sppl3 cleaves many of them and thereby controls protein glycosylation at multiple levels. Therefore, to systematically identify Sppl3 substrates we used Sppl3-deficient and Sppl3-overexpression cell culture models and analyzed them for changes in secreted membrane protein ectodomains using the proteomics "secretome protein enrichment with click sugars (SPECS)" method. SPECS analysis identified numerous additional new Sppl3 candidate glycoprotein substrates, several of which were biochemically validated as Sppl3 substrates. All novel Sppl3 substrates adopt a type II topology. The majority localizes to the Golgi network and is implicated in Golgi functions. Importantly, most of the novel Sppl3 substrates catalyze the modification of N-linked glycans. Others contribute to O-glycan and in particular glycosaminoglycan biosynthesis, suggesting that Sppl3 function is not restricted to N-glycosylation, but also functions in other forms of protein glycosylation. Hence, Sppl3 emerges as a crucial player of Golgi function and the newly identified Sppl3 substrates will be instrumental to investigate the molecular mechanisms underlying the physiological function of Sppl3 in the Golgi network and in vivo. Data are available via ProteomeXchange with identifier PXD001672.
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PMID:Secretome analysis identifies novel signal Peptide peptidase-like 3 (Sppl3) substrates and reveals a role of Sppl3 in multiple Golgi glycosylation pathways. 2582 71