Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.99.7 (sialyltransferase)
 1,534 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To characterize the sialyltransferase-IV activity in brain tissues, the activities of GM1b-, GD1a-, GT1b-, and GQ1c-synthases in adult cichlid fish and rat brains were examined using GA1, GM1, GD1b, or a cod brain ganglioside mixture as the substrate. The GD1a-synthase activity in the total membrane fraction from cichlid fish brain required divalent cations such as Mg2+ or Mn2+ and Triton CF-54 for its full activity. The Vmax value was 1,340 pmol/mg of protein/h at an optimal pH of 6.5, whereas the apparent Km values for CMP-sialic acid and GM1 were 172 and 78 microM, respectively. Cichlid fish and rat brains also contained GM1b-, GT1b-, and GQ1c-synthase activities. The ratio of GM1b-, GD1a-, and GT1b-synthase activities in fish brain was 1.00:0.89:1.13, respectively, and in rat brain 1.00:0.60:0.63. Incubation of fish brain membranes with a cod brain ganglioside mixture, which contains GT1c, and [3H]CMP-sialic acid produced radiolabeled GQ1c. It is interesting that the adult rat brain also contains an appreciable level of GQ1c-synthase activity despite its very low concentrations of c-series gangliosides. The GD1a- or GQ1c-synthase activity in fish and rat brain was inhibited specifically by coincubation with the glycolipids that serve as the substrates for other sialyltransferase-IV reactions. Thus, the GD1a-synthase activity was inhibited by GA1 and GD1b, but not by LacCer, GM3, or GD3. In a similar manner, the synthesis of GQ1c was suppressed by GA1, GM1, and GD1b, but not by LacCer, GM3, or GD3.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of sialyltransferase-IV activity and its involvement in the c-pathway of brain ganglioside metabolism. 779 36

A human Gal beta(1-3/1-4)GlcNAc alpha 2,3-sialyltransferase, called ST-4, is a sialyltransferase involved in the in vivo biosynthesis of sialyl Lewis X (NeuNAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc) determinant. The ST-4 enzyme could utilize nLc4Cer (Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer) containing type 2 sugar chain, Lc4Cer (Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer) containing type 1 sugar chain, Gg4Cer (Gal beta 1-3GalNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer), and LacCer as glycolipid acceptor substrates, but not other neutral glycolipids (GalCer, GlcCer, Gb3Cer, Gg3Cer, Gb4Cer) and gangliosides (GM1a, GM2, GM3, GD1a, GD1b, and GT1b) as substrates. The order of sialic acid incorporation into glycolipids for the enzyme was nLc4Cer > Gg4Cer > Lc4Cer > LacCer. The apparent Km values of ST-4 for nLc4Cer and Gg4Cer were 0.47 and 2.5 mM, respectively. Thus, the ST-4 could efficiently utilize both nLc4Cer and Gg4Cer as glycolipid acceptor substrates in vitro, suggesting that the substrate specificity of the enzyme may be similar to that of a glycolipid sialyltransferase (SAT-3), which is defined as the enzyme that uses both nLc4Cer and Gg4Cer as glycolipid acceptor substrates.
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PMID:Glycolipid acceptor specificity of a human Gal beta(1-3/1-4) GlcNAc alpha 2,3-sialyltransferase. 855 8

Retinoic acid (RA) plays an important role in differentiation stage in which it also influences glycoconjugate metabolism. Previous work in our laboratory has shown that treatment with RA modifies glycolipid synthesis and distribution in total Xenopus embryos during development. In this study we have investigated the activity of the following anabolic enzymes involved in glycolipid biosynthesis: sialyltransferase-1 (SAT-1), GM3(beta1, 4)-N-acetylgalactosaminyltransferase (GalNAcT-1) and LacCer(beta1, 3)N-acetylglucosaminyltransferase (GlcNAcT-1). These enzymes are located at the branching point of lactosylceramide (Lc(2)) metabolism. Enzyme activities were assayed after treatment with different doses of RA added exogenously to the medium during the first 7 days of Xenopus embryo development. Our results show that RA activates GlcNAcT-1, the enzyme that drives Lc(2)to the glycolipids of the lacto-series, and SAT-1 that inserts Lc(2)in the ganglio-series pathway. These data support our previous analysis of glycolipid pattern in Xenopus embryos after RA treatment (Rizzo et al., 1995;Cell Biol Int19: 895-901) indicating a possible correlation between the distribution of glycolipids and the enzymes involved in their metabolism.
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PMID:Glycolipid glycosyltransferase activities during early development of Xenopus: effect of retinoic acid. 1056 Nov 17

The effect of changing the ganglioside composition of Chinese hamster ovary K1 cells on the function of the epidermal growth factor receptor (EGFr) was examined by studying the signalling pathway generated after the binding of epidermal growth factor (EGF) both in cells depleted of glycosphingolipids by inhibiting glucosylceramide synthase activity and in cell lines expressing different gangliosides as the result of stable transfection of appropriate ganglioside glycosyltransferases. After stimulation with EGF, cells depleted of glycolipids showed EGFr phosphorylation and extracellular signal-regulated protein kinase 2 (ERK2) activity as parental cells expressing GM3 [ganglioside nomenclature follows Svennerholm (1963) J. Neurochem. 10, 613-623] or as transfected cells expressing mostly GM2 and GD1a as the result of stable transfection of UDP-GalNAc:LacCer/GM3/GD3 N-acetylgalactosaminyltransferase. However, cells stably transfected with CMP-NeuAc:GM3 sialyltransferase and expressing GD3 at the cell surface showed both decreased EGFr phosphorylation and ERK2 activation after stimulation with EGF. Results suggest that changes in the ganglioside composition of cell membranes might be important in the regulation of the EGF signal transduction.
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PMID:Modulation of epidermal growth factor receptor phosphorylation by endogenously expressed gangliosides. 1128 35

Glycolipids in the thymus of mice after administration of dexamethasone were compared with those in control mice. In parallel with a decrease in the tissue weight due to the disappearance of immature thymocytes in the cortex, the amounts of GlcCer, Gg4Cer and GM1 decreased from 18 h after intraperitoneal administration of dexamethasone, but those of Gb4Cer and Forssman glycolipid did not change, indicating the differential distribution of ganglio- and globo-series glycolipids in the thymus, GlcCer, Gg4Cer and GM1 being on dexamethasone-sensitive cortical thymocytes, and Gb4Cer and Forssman glycolipid on dexamethasone-resistant cells including thymic stromal cells, respectively. At the same time, a characteristic increase in GM3, whose amount per thymus and concentration per mg of thymus were increased 4-fold and 13-fold compared to those in the control mice, respectively, was observed at the onset of the decrease in tissue weight and was due to the increased activity of LacCer sialyltransferase with the enhanced expression of its gene and the concomitant decrease in cytosolic sialidase activity. One can suggest that endogenous accumulation of GM3 is involved in the dexamethasone-induced apoptosis of cortical thymocytes. On radiolabeling of the thymus with CMP-[14C]-NeuAc, the incorporation of radioactivity into GM3 was preferentially observed in the thymuses of dexamethasone-administered mice, but not in those of control mice, suggesting the possible involvement of plasma membrane-associated sialytransferase in GM3 synthesis in the thymuses of dexamethasone-administered mice.
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PMID:Changes in the glycolipid composition and characteristic activation of GM3 synthase in the thymus of mouse after administration of dexamethasone. 1613 32

Gangliosides, complex glycosphingolipids containing sialic acids, are synthesized in the endoplasmic reticulum and in the Golgi complex. These neobiosynthesized gangliosides move via vesicular transport to the plasma membrane, becoming components of the external leaflet. Gangliosides can undergo endocytosis followed by recycling to the cell surface or sorting to the Golgi complex or lysosomes for remodeling and catabolism. Recently, glycosphingolipid catabolic enzymes (glycohydrolases) have been found to be associated with the plasma membrane, where they display activity on the membrane components. In this work, we demonstrated that ecto-ganglioside glycosyltransferases may catalyze ganglioside synthesis outside the Golgi compartment, particularly at the cell surface. Specifically, we report the first direct evidence of expression and activity of CMP-NeuAc:GM3 sialyltransferase (Sial-T2) at the cell surface of epithelial and melanoma cells, with membrane-integrated ecto-Sial-T2 being able to sialylate endogenously synthesized GM3 ganglioside as well as exogenously incorporated substrate. Interestingly, we also showed that ecto-Sial-T2 was able to synthesize GD3 ganglioside at the cell surface using the endogenously synthesized cytidine monophospho-N-acetylneuraminic acid (CMP-NeuAc) available at the extracellular milieu. In addition, the expression of UDP-GalNAc:LacCer/GM3/GD3 N-acetylgalactosaminyltransferase (GalNAc-T) was also detected at the cell surface of epithelial cells, whose catalytic activity was only observed after feeding the cells with exogenous GM3 substrate. Thus, the relative interplay between the plasma membrane-associated glycosyltransferase and glycohydrolase activities, even when acting on a common substrate, emerges as a potential level of regulation of the local glycosphingolipid composition in response to different external and internal stimuli.
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PMID:Neobiosynthesis of glycosphingolipids by plasma membrane-associated glycosyltransferases. 2063 93


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