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)

Two variant mouse L cell lines (termed CL 3 and CL 6) have been selected for resistant to ricin, a galactose-binding lectin with potent cytotoxic activity. The resistant lines exhibit a 50 to 70% decrease in ricin binding and a 300- to 500-fold increase in resistance to the toxic effects of ricin. Crude membrane preparations of CL 3 cells have increased sialic acid content (200% of control), while the galactose, mannose, and hexosamine content is within normal limits. Both the glycoproteins and glycolipids of CL 3 cells have increased sialic acid, with the GM3:lactosylceramide ratios for parent L and CL 3 cells being 0.29 and 1.5, respectively. In contrast, the membranes of CL 6 cells have a decrease in sialic acid, galactose, and hexosamine content with mannose being normal. Both cell lines have specific alterations in glycosyltransferase activities which can account for the observed membrane sugar changes. CL 3 cells have increased CMP-sialic acid:glycoprotein sialyltransferase and GM3 synthetase activities, while CL 6 cells have decrease UDP-GlcNAc:glycoproteinN-acetylglucosaminyltransferase and DPU-galactose:glycoprotein galactosyltransferase activities. The increased sialic acid content of CL 3 cells serves to mask ricin binding sites, since neuraminidase treatment of this cell line restores ricin binding to essentially normal levels. However, the fact that neuraminidase-treated CL 3 cells are still 45-fold resistant to ricin indicates that either a special class of productive ricin binding sites is not being exposed or that the cell line has a second mechanism for ricin resistance.
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PMID:Isolation and characterization of two mouse L cell lines resistant to the toxic lectin ricin. 100 11

The postnatal developmental profiles of the protein-bound sialic acid content and the activities of CMP-N-acetylneuraminic acid (CMP-AcNeu) synthetase (EC 2.7.7.43) and glycoprotein sialyltransferase, enzymes involved in sialoglycoprotein biosynthesis, were estimated in the rat brain. The sialoglycoprotein level appeared to increase 2-fold from birth to about 20 days of age, which correlates with the outgrowth of the cell processes in this period. In contrast, the activities per g wet tissue of the enzymes were highest at birth and showed decreasing tendencies during maturation. This revealed that, at least at a certain stage during development, the sialyltransferase is present in structures other than synaptic membranes, since the new-born rat brain is devoid of these membranes. The developmental profile of the endogenous, sialic acid accepting molecules was very similar to that of the sialoglycoproteins. It was concluded that cerebral sialoglycoprotein biosynthesis during postnatal development is not limited by the activities of the synthetase and the transferase, but may largely depend on the production of the endogenous acceptors, which are presumed to be the natural precursors for the sialoglycoproteins.
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PMID:Sialoglycoprotein synthesis in developing rat brain. 117 8

CMP-N-acetylneuraminic acid: glycoprotein sialyltransferase activities were assayed in rat liver microsomal fractions using desialylated fetuin as the substrate acceptors for N-acetylneuraminic acid. It was found that cytidine nucleotides specifically depressed enzyme activities. CMP was shown to act as a competitive inhibitor with an apparent Ki of 0.62 mM. N-Acetylneuraminic acid at 1.15 mM had no effect on enzyme activities. Uridine nucleotides at 1.15 mM, especially UDP, increased enzyme activities. UDP may act as an allosteric activating agent increasing the apparent V. Other nucleotides, sugars and nucleotide-sugars at similar concentrations affected sialyltransferase activities only slightly. A general mechanism is proposed for the regulation of glycosyltransferase activities by free nucleotides.
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PMID:Regulation of rat-liver glycoprotein: N-acetylneuraminic acid transferase activity by pyrimidine nucleotides. 118 47

Sialyltransferase activity (EC 2.4.99.6) was measured in the microsomal fraction of colorectal cancer cell lines using an assay based on the incorporation of [14C]CMP-sialic acid into asialofetuin. In the poorly differentiated lines MIP101 and Clone A, sialyltransferase activity had a Vmax of 0.36 and 0.31 nmol/mg protein/h, respectively, while the moderately differentiated to well-differentiated cell lines HT-29, CCL188, and CX-1 had Vmaxs of 2.46, 1.05, and 1.24 nmol/mg protein/h, respectively. All cell lines tested had a Km of 15.4 (+/- 0.7)(SD) mumol/liter. The better differentiated cells had higher levels of sialyltransferase activity, which correlated with their higher levels of sialic acid and their enhanced ability to form liver metastases in the nude mouse following intrasplenic injection compared to the poorly differentiated cell lines. Treatment of the cell lines with KI-8110, a CMP-sialic acid derivative which prevents incorporation of sialic acid into glycoconjugates, resulted in reduced formation of hepatic metastases by the colorectal carcinoma cell lines in the nude mouse model. It is suggested that reduced sialylation of adhesion molecules such as carcinoembryonic antigen may change the biology of the tumor cell, one consequence of which is the prevention of implantation of the cells into distant sites, resulting in a reduced incidence of metastases.
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PMID:Sialyltransferase activity and hepatic tumor growth in a nude mouse model of colorectal cancer metastases. 131 99

Bovine colostrum CMP-NeuAc:Gal beta(-->4)GlcNAc-R alpha(2-->6)-sialyltransferase (alpha 6-sialyltransferase) appears to be capable of catalysing alpha 6-sialylation of the disaccharide GalNAc beta(1-->4)GlcNAc to yield the trisaccharide NeuAc alpha(2-->6)GalNAc beta(1-->4)GlcNAc. This provides an enzymic basis for the occurrence of this sialylated structure on the N-linked glycans of a number of bovine milk glycoproteins. Competition experiments using Gal beta(1-->4)GlcNAc and GalNAc beta(-->4)GlcNAc as acceptors indicate that both substrates are recognized by a single active site on the alpha 6-sialyltransferase. Extrapolation of these results suggests that the NeuAc alpha(2-->6)GalNAc beta(1-->4)GlcNAc structural element occurring on the N-linked glycans of several human glycoproteins are similarly synthesized by the action of a Gal beta(1-->4)GlcNAc-R alpha(2-->6)-sialyltransferase.
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PMID:Bovine colostrum CMP-NeuAc:Gal beta(1-->4)GlcNAc-R alpha(2-->6)-sialyltransferase is involved in the synthesis of the terminal NeuAc alpha(2-->6)GalNAc beta(1-->4)GlcNAc sequence occurring on N-linked glycans of bovine milk glycoproteins. 141 84

The resistance of gonococci in most patients to complement mediated killing by human serum is due to sialylation of their lipopolysaccharide (LPS) which prevents bactericidal antibody from reacting with target sites. Two of the host factors responsible are: cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA), a well-known sialylating agent, and another factor which enhances the transfer of sialyl groups from CMP-NANA to LPS catalysed by a gonococcal sialyltransferase. The bacterial determinant of resistance is a conserved LPS component of about 4.5 kDa which is sialylated at a terminal Gal beta 1-4GlcNAc site on its side chain. The sialylated LPS forms a surface coat which is stainable by ruthenium red and connected with previously described 'capsules'. These observations sparked off an explosion of research. Recent publications show that sialylation of LPS by CMP-NANA affects additional important aspects of gonococcal pathogenicity, notably interactions with antibodies and phagocytes, and rendering the gonococcal surface more 'host-like'. Also, the observations have prompted an examination of LPS from some other pathogens for the presence of sialyl groups with positive results for Neisseria meningitidis and Haemophilus influenzae.
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PMID:The sialylation of gonococcal lipopolysaccharide by host factors: a major impact on pathogenicity. 147 64

A high relative molecular mass (M(r)) component which confers serum resistance on gonococci has been purified about 300-fold from a dialysed sonicate of human blood cells. Serum resistance conferred by the high M(r) factor (RIF), like that induced by cytidine-5' monophospho-N acetyl neuraminic acid (CMP-NANA), decreased when gonococci were incubated with neuraminidase. Also, the resistance-inducing activities of both high M(r) RIF and CMP-NANA were inhibited by CMP and inactivated at pH 4.0. These activities were not additive but synergistic. Neuraminidase decreased the activity of high M(r) RIF but not CMP-NANA. In tests with 14C CMP-NANA and gonococcal lipopolysaccharide, no sialyltransferase activity was detected, even in highly active samples of high M(r) RIF under conditions in which low activities of rat liver sialyltransferase were readily detected. Conversely, rat liver sialyltransferase was neither active in the RIF assay nor able to enhance the RIF activity of CMP-NANA. Nevertheless, high M(r) RIF greatly enhanced the sialyltransferase activity of a gonococcal extract; this enhancement suggests an explanation for the synergism between CMP-NANA and high M(r) RIF in inducing serum resistance in gonococci.
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PMID:A high Mr factor in human blood which confers serum resistance on gonococci: some properties and synergism with CMP-NANA. 152 97

Many previous studies have implicated cell surface saccharides, and sialylglycoconjugates in particular, as important mediators of tumor cell metastasis. In this report, we have used three different specific sialidases and a highly sensitive high-performance liquid chromatographic sialic acid assay to probe the cell surfaces of several murine adrenal carcinoma variants. In contrast to several earlier studies on other metastatic variants, we find no significant differences in the overall levels of cell surface or total cellular sialic acid among three Y1 murine adrenal carcinoma variants with widely different metastatic phenotypes. However, using highly purified, linkage-specific sialyltransferases, in conjunction with V. cholerae sialidase, to probe the cell surface saccharide topography of specific penultimate oligosaccharides, we do find striking differences in oligosaccharide structures underlying the sialic acid moieties. Two tumorigenic and metastatic variants (F2 and F4) contain about 6-fold more penultimate Gal beta 1----4GlcNAc sialylation sites than a related tumorigenic but nonmetastatic variant (HSR) when CMP-[3H]-N-acetylneuraminic acid and the Gal beta 1----4GlcNAc alpha 2,6 sialyltransferase are used to probe the adrenal carcinoma cell surfaces. The metastatic variants also are found to contain 4- to 4.5-fold more Gal beta 1----3GalNAc sialylation sites than the nonmetastatic variant when the Gal beta 1----3GalNAc alpha 2,3 sialyltransferase is used as a cell surface probe. Earlier work, which used the same sialyltransferase probes on sialidase-treated murine melanoma variants (A. Passaniti and G. W. Hart, J. Biol. Chem., 263: 7591-7603, 1988), also showed similar quantitative differences in penultimate structures between metastatic variants. However, in contrast to the adrenal carcinoma cells, the highly metastatic melanoma cells have severalfold lower levels of sialylatable penultimate Gal beta 1----4GlcNAc and Gal beta 1----3GalNAc saccharides compared to their nonmetastatic counterparts. Thus, while the precise structural alterations or surface accessibilities of penultimate saccharides appear to be cell type dependent, these results suggest that pronounced changes in penultimate cell surface sialo-oligosaccharide moieties occur during progression to a malignant phenotype in two widely different tumor systems. These types of alterations in the underlying penultimate oligosaccharide structures of cell surface sialoglycoconjugates may be a common feature of highly metastatic cells arising from very different tumor cell types.
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PMID:Adrenal carcinoma tumor progression and penultimate cell surface oligosaccharides. 155 26

Sialyltransferases (CMP-N-acetylneuraminic acid:glycoprotein sialyltransferases, EC 2.4.99.1) are involved in the transfer of a sialic acid moiety from CMP-N-acetylneuraminic acid (CMP-NeuAc) to an oligosaccharide side-chain of an acceptor, asialoglycoprotein (AGP), according to the following reaction: CMP-NeuAc + AGP----NeuAc-O-AGP + CMP. This enzyme occurs in elevated levels in the sera of patients with a wide variety of neoplastic diseases and its assay might be useful in monitoring treatment. Radioactive CMP-NeuAc has been used in assays and the radioactive sialylated product separated and counted by liquid scintillation spectrometry. This study shows that a simple, rapid, non-radiochemically based high-performance liquid chromatographic method developed for the analysis of CMP-sialic acid synthetase can be used for the quantitation of sialyltransferase activity by monitoring simultaneously the utilization of CMP-NeuAc and the release of CMP. We describe the application of this method to assay of commercially available sialyltransferase activity and to activities from synovial, ascites and gastric fluids.
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PMID:Assay of sialyltransferase activity by reversed-phase ion-pair high-performance liquid chromatography. 156 2

Human chorionic gonadotrophin (hCG) is a heterodimeric glycoprotein hormone consisting of an alpha- and a beta-subunit, both containing two N-linked, complex-type glycans. Using this hormone as a model glycoprotein, the influence of its polypeptide part on the activity and specificity of bovine colostrum CMP-NeuAc:Gal beta 1----4GlcNAc-R alpha 2----6-sialyltransferase (alpha 6-sialyltransferase) was investigated. Initial rates of sialic acid incorporation into the desialylated glycans of hCG alpha and hCG beta in the heterodimer were higher with the alpha-subunit. This appeared to be due to a higher V which, together with a slightly lowered affinity (higher Km), resulted in a higher kinetic efficiency of the sialyltransferase for the glycans of this subunit. By contrast, the kinetic parameters did not differ significantly when the subunits were in the free form, indicating that the differences in the kinetics of sialylation found for the subunits in the heterodimeric state were not caused by the differences in N-linked carbohydrate structures of the subunits. It is proposed that these effects are due to conformational constraints which the polypeptide moieties put on the glycan chains upon dimerization. Furthermore, it was investigated whether the polypeptide of hCG would interfere with the sialyltransferase so as to alter the branch specificity of the enzyme. 1H-NMR spectroscopy (400 MHz) of the glycan chains, alpha 6-sialylated in vitro, showed that the enzyme highly prefers the galactosyl residue at the Gal beta 1----4GlcNAc beta 1----2-Man alpha 1----3Man branch for attachment of the first mol of sialic acid into the diantennary glycans of desialylated hCG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The polypeptide part of human chorionic gonadotrophin affects the kinetics of alpha 6-sialylation of its N-linked glycans but does not alter the branch specificity of CMP-NeuAc:Gal beta 1----4GlcNAc-R alpha 2----6-sialyltransferase. 160 56


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