Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.99.10 (sialyltransferase)
 1,547 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rabbits were subjected to 3 h of hyperthermia at 40 degrees C. The phospholipid content of the brain was unchanged, whereas the free fatty acids increased by about 73% over control levels. Hyperthermia also induced inhibition of fatty acid peroxidation processes. The last products of fatty acid peroxidation, the thiobarbituric acid reactive substances, diminished significantly during hyperthermia, whereas the level of the first intermediate of this pathway, the conjugated double bonds, remained unchanged. Simultaneously, the levels of lipid-soluble antioxidants decreased significantly. The content of free fatty acids, malondialdehyde, and lipid-soluble anti-oxidant returned toward control levels during 3 h of recovery. The content of gangliosides was 10-20% above control values in the groups of animals examined immediately and 3 h after hyperthermia. The ganglioside-specific enzymes, neuraminidase and sialyltransferase, both directed toward endogenous lipid substrates, were activated by hyperthermia, suggesting the stimulation of turnover of the gangliosides during the course of hyperthermia. Lipid alterations resulting from short-term hyperthermia may influence the physicochemical properties of neuronal membranes.
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PMID:Rabbit brain lipids during short-term hyperthermia. 356 91

Because alterations in cell membrane sialoglycoconjugates can affect the behavior of neoplastic cells, we investigated the effects of in vitro treatment with antimetabolites used in cancer therapy on the expression of membrane sialic acid in cultured HL-60 leukemic cells. In these studies, cells were incubated with Vibrio cholerae neuraminidase to remove surface sialic acid. Reappearance of membrane sialic acid during drug treatment was followed (a) by measuring changes in radioactive surface labeling of viable cells with sodium metaperiodate-sodium[3H]-borohydride, (b) by measuring the decline in accessible surface galactosyl receptor sites which occurred coincident with membrane sialic acid replacement, and (c) by measuring the incorporation of [3H]glucosamine into membrane-associated neuraminidase-labile sialic acid. We were especially interested in learning whether drugs that affect intracellular pools of cytidine triphosphate (CTP), an important nucleotide intermediate in sialylation reactions, could inhibit regeneration of membrane sialic acid. 3-Deazauridine, a competitive inhibitor of CTP synthetase, depleted CTP pools and curtailed surface membrane resialylation with little or no effect on synthesis of de novo sialic acid from precursor sugars. The addition of cytidine restored CTP pools and sialic acid regeneration. Acivicin, a glutamine antagonist, also depleted CTP pools and curtailed surface membrane resialylation. In addition, it retarded de novo synthesis of sialic acid. The addition of cytidine restored intracellular CTP pools and sialic acid regeneration. However, both cytidine and guanosine were required to restore sialic acid synthesis from precursor sugars. 1-beta-D-Arabinofuranosylcytosine, a competitive inhibitor of sialic acid synthetase and of sialyltransferase, inhibited both de novo sialic acid synthesis and membrane resialylation. Only the latter effect was reversed by the addition of exogenous cytidine. Hydroxyurea, an agent shown previously to inhibit glycoconjugate production in hamster fibroblasts, curtailed membrane resialylation and de novo synthesis of sialic acid without depleting CTP pools. Doxorubicin, at levels that caused marked arrest of cell proliferation, had no effect on sialic acid synthesis or expression on the membrane surface. These data suggest that antimetabolites, apart from their cytotoxic effects or effects on cellular growth, may directly inhibit the expression of membrane sialic acid.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of pyrimidine antagonists on sialic acid regeneration in HL-60 cells. 385 65

Neisseria meningitidis serogroup B strain M986 was examined for the involvement of lipid intermediate(s) participating in the biosynthesis of the sialic acid capsular polysaccharide. The addition of exogenous undecaprenyl phosphate, phosphatidylethanolamine, or phosphatidylglycerol to particulate membranes, in the presence of cytidine 5'-monophosphosialic acid, resulted in the stimulation of sialyltransferase activity specifically by undecaprenyl phosphate. Sialyltransferase activity, after delipidation of particulate membrane proteins, was specifically reconstituted by undecaprenyl phosphate. After the addition of 14C-labeled cytidine 5'-monophosphosialic acid to particulate membranes, the level of labeled lipid intermediate(s), extracted by chloroform-methanol (2:1), increased up to a maximum level between 3.75 and 5.0 min, which subsequently decreased to a lower steady-state level. Pulse-chase experiments revealed a transient, solvent-extractable, lipid-linked component. The extracted N-acetylneuraminic acid was in polymeric form. Sequential oxidation and reduction of the extracted radioactivity followed by neuraminidase treatment revealed an average degree of polymerization of four or five N-acetylneuraminic acid residues. Bacitracin-sensitive peptidoglycan was synthesized in vitro by particulate membranes. Cross-competition experiments between peptidoglycan and capsular polysaccharide synthesis by preincubation of precursors of one pathway during synthesis of the other revealed a competitive effect for a common component. This component was believed to be a common pool of undecaprenyl phosphate. A model for the production and regulation of the capsular polysaccharide is proposed.
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PMID:Role of lipid intermediate(s) in the synthesis of serogroup B Neisseria meningitidis capsular polysaccharide. 391 90

A sialyltransferase which catalyzes the in vitro biosynthesis of N-acetylneuraminosyllacto-N-neohexaosylceramide from lacto-N-neohexaosylceramide and CMP-NeuAc has been examined in embryonic chicken breast muscle. The maximum enzyme activity was observed in 11-12-day-old embryos. The enzyme has optimum activity at pH 6.8 in the presence of Triton CF-54 and Mg2+. The apparent Km values for lacto-N-neohexaosylceramide and CMP-NeuAc were 0.9 and 0.67 mM, respectively. The enzymic product was characterized by TLC, neuraminidase hydrolysis and permethylation analysis. The structure was identical to authentic N-acetylneuraminosyllacto-N-neohexaosylceramide from chicken muscle. In addition, a disialo derivative has been detected that constitutes 15% of the total radioactivity incorporated. The two sialic acids connected by sialosyl-sialosyl linkage were attached to the terminal galactose residue. To our knowledge, this is the first report of biosynthesis of this disialo compound.
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PMID:Sialylation of lacto-N-neohexaosylceramide by sialyltransferase from embryonic chicken muscle. 395 72

Sialyltransferase was measured in serum of normal and hepatoma Mc-29 bearing chickens. By preparative isoelectric focusing the multiple forms of sialyltransferase from both kind of serums was studied as well. By using influenza virus neuraminidase an attempt was made for partial structural characterization of the sialylation sites in asialofetuin applied as exogenous acceptor for sialyltransferase determination. It was established an elevated serum sialyltransferase activity in tumor bearing chickens with tumor an enzyme form was detected with pI-4.99 identical with an enzyme form described previously in solubilized plasma membrane preparations from hepatoma Mc-29. Monitoring of multiple forms of serum glycosyltransferases may be of value in answering the problem concerning the tissue origin of serum enzymes.
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PMID:Characterization of sialyltransferases from serum of normal and hepatoma Mc-29 bearing chickens. 395 42

A cancer-associated glycolipid antigen defined by monoclonal antibody 19-9 has the structure NeuAc alpha 2-3Gal Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc beta 1-Cer. We have (formula; see text) studied its biosynthesis by testing the capacity of a crude microsomal fraction of SW 1116 cells to catalyze the addition of fucosyl or sialyl residues from GDP-fucose or CMP-sialic acid to glycolipid or oligosaccharide precursors. When the tetrasaccharide NeuAc alpha 2-3Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc (LSTa) is incubated with GDP-[14C]fucose and SW 1116 microsomes, a 14C-labeled oligosaccharide is formed that can be separated from the incubation mixture on an affinity column containing antibody 19-9 bound to protein A-Sepharose. The product migrates slower than LSTa when analyzed by paper or thin-layer chromatography. After treatment with neuraminidase, it co-migrates with the pentasaccharide Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc (formula; see text) (LNF II) in both chromatographic systems. Similar experiments demonstrate that SW 1116 microsomes catalyze the addition of a sialyl residue to the tetrasaccharide Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc to form LSTa. However, when LNF II is incubated with CMP-[14C]sialic acid and SW 1116 microsomes, no 19-9-active product is detected by affinity chromatography or by paper or thin-layer chromatography. Results using glycolipid precursors are consistent with these findings and also demonstrate the presence of the Lewis fucosyltransferase in SW 1116 cells. Thus, the biosynthesis of the sialyl-Lea antigen proceeds by addition of sialic acid to a type 1 precursor chain by a sialyltransferase, followed by addition of fucose by the Lewis fucosyltransferase.
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PMID:Biosynthesis of the cancer-associated sialyl-Lea antigen. 401 78

Fetal calf liver microsomes were found to be capable of sialylating 14C-galactosylated ovine submaxillary asialomucin. The main oligosaccharide product chain could be obtained by beta-elimination under reductive conditions and was identified as NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAcol (where GalNAcol represents N-acetylgalactosaminitol) by means of high performance liquid chromatography (HPLC) analysis and methylation. The branched trisaccharide Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)-GalNAcol and the disaccharide NeuAc alpha 2 leads to 6GalNAcol were not formed. Very similar results were obtained when asialofetuin and antifreeze glycoprotein were used as an acceptor. When 3H-sialylated antifreeze glycoprotein ([3H]NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc-protein) was incubated with fetal calf liver microsomes and CMP-[14C]NeuAc, a reduced tetrasaccharide could be isolated. The structure of this product chain appeared to be [3H]NeuAc alpha 2 leads to 3Gal beta 1 leads to 3([14C]NeuAc alpha 2 leads to 6)GalNAcol, as established by means of HPLC analysis, specific enzymatic degradation with Newcastle disease virus neuraminidase, and periodate oxidation. These data indicate that fetal calf liver contains two sialyltransferases involved in the biosynthesis of the O-linked bisialotetrasaccharide chain. The first enzyme is a beta-galactoside alpha 2 leads to 3 sialyltransferase which converts Gal beta 1 leads to 3 GalNAc chains to the substrate for the second enzyme, a (NeuAc alpha 2 leads to 3Gal beta 1 leads to 3)GalNAc-protein alpha 2 leads to 6 sialyltransferase. The latter enzyme does not sialylate GalNAc or Gal beta 1 leads to 3GalNAc units but is capable of transferring sialic acid to C-6 of GalNAc in NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc trisaccharide side chains, thereby dictating a strictly ordered sequence of sialylation of the Gal beta 1 leads to 3 GalNAc units in fetal calf liver.
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PMID:Biosynthesis of the O-glycosidically linked oligosaccharide chains of fetuin. Indications for an alpha-N-acetylgalactosaminide alpha 2 leads to 6 sialyltransferase with a narrow acceptor specificity in fetal calf liver. 619 Aug 2

Neuraminidase activity of Rous sarcoma virus transformed chick embryo fibroblasts (RSV-CEF) was assayed using an exogenous substrate, neuraminlactitol-[3H], and endogenous, cell surface [14C]-N]-acetyl-neuraminic acid. RSV-CEF had higher neuraminidase activity toward both substrates than did chick embryo fibroblasts (CEF) or nontransformed, Rous associated virus infected CEF (RAV-CEF). The total sialic acid content of RSV-CEF was lower than CEF or RAV-CEF, and more of the total sialic acid was accessible to extracellular Clostridium perfringens neuraminidase. Activity of the enzymes synthesizing and degrading the substrate for sialyltransferase, cytidine-5'-monophosphate-N-acetyl-neuraminic acid (CMP-AcNeu) was measured in order to determine whether control of substrate levels for sialyltransferase might contribute to the decreased levels of glycoprotein bound sialic acid. No change in activity of these enzymes was found in RSV-CEF as compared to CEF or RAV-CEF.
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PMID:Neuraminidase activity and cell surface sialic acid turnover in Rous sarcoma virus transformed chick embryo fibroblasts. 626 45

Three prokaryotic-derived probes to identify and study the temporal expression of polysialosyl units in neuronal tissue have been developed. A polyclonal antibody, a bacteriophage-derived endo-neuraminidase, and an Escherichia coli K1 sialyltransferase are all specific for either recognizing or synthesizing poly(sialic acid) containing alpha-2,8-ketosidic linkages. Polysialosyl immunoreactivity with apparent Mr values of 180,000-240,000 was specific for developing neuronal tissue; it was not detected in neonatal liver or kidney or in adult brain tissue. The developmentally regulated disappearance in poly(sialic acid) is consistent with the probes described here recognizing the polysialosyl carbohydrate units of a neuronal cell adhesion molecule (N-CAM). Treatment of brain extracts with a bacteriophage-derived endo-neuraminidase specific for alpha-2,8-linked polysialosyl units abolished the immunoreactivity. The material solubilized by endo-neuraminidase was isolated, reduced with borotritide, and shown to contain oligomers of sialic acid with three to six sialyl units. Treatment of the 3H-labeled oligosialic acid with exo-neuraminidase quantitatively converted the radioactivity to sialitol, establishing that the brain-derived oligomers were composed solely of sialic acid. A membranous sialytransferase from E. coli K1 that can transfer sialic acid to exogenous acceptors of oligo- or poly(sialic acid) also recognized rat brain membranes, further substantiating the presence of poly(sialic acid) in rat brain. This conclusion was confirmed by using a mutant of E. coli K1 that was defective in the synthesis of poly(sialic acid) and could only transfer sialic acid to exogenous acceptors of oligo- or poly(sialic acid). Sialyl polymer synthesis was restored in the mutant when brain membranes were added as exogenous acceptor.
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PMID:Use of prokaryotic-derived probes to identify poly(sialic acid) in neonatal neuronal membranes. 637 6

In order to study structure-function relationships of lysosomal enzymes, human liver beta-N-acetylhexosaminidase (2-acetamido-2-deoxy-beta-D-hexoside acetamidodeoxyhexohydrolase, EC 3.2.1.52) has been purified by an extraction/affinity chromatography/ion-exchange procedure. The isoenzymes A and B, native as well as neuraminidase-treated, were incubated with a partially purified preparation of bovine colostrum sialyltransferase (CMP-N-acetylneuraminate: D-galactosyl-glycoprotein N-acetylneuraminyltransferase, EC 2.4.99.1). Native beta-N-acetylhexosaminidases were found to be poor acceptors for the sialyltransferase used. However, incorporation of sialic acid into neuraminidase-treated beta-N-acetylhexosaminidase A and B amounted to a 58 to 72% saturation of the theoretical acceptor sites, respectively. The acceptor specificity of the sialyltransferase suggests that Gal beta(1 leads to 4)-GlcNAc units may be present on at least part of the beta-N-acetylhexosaminidase A and B molecules. However, oligomannosidic-type chains may also occur on the lysosomal enzyme, as shown by sugar composition of the enzyme. The presence and/or amount of sialic acid residues does not appear to affect the kinetic properties of beta-N-acetylhexosaminidase A and B towards 4-methylumbelliferyl glycoside substrate.
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PMID:Sialylation in vitro of purified human liver beta-D-N-acetylhexosaminidase. 645 69


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