Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.4.99.6 (sialyltransferase)
1,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of sialytransferase with regard to the glycoprotein substrates asialofetuin and asialo-ovine submaxillary mucin was determined in normal, pathological control, and cystic fibrosis liver homogenates. Cystic fibrosis and pathological livers have about 40% of the average normal specific activity for sialytransferase. Several properties of cystic fibrosis sialytransferase were investigated and compared to those of the normal liver enzyme (Alhadeff et al. 1977). The pH optima curves were similar, but cystic fibrosis sialyltransferase appears to be more thermolabile than the normal liver enzyme. Isoelectric focusing studies revealed that the three most basic forms of sialyltransferase which are found in normal livers are deficient or absent in most cystic fibrosis liver. The data suggest that altered glycoprotein-sialyltransferases may be present in cystic fibrosis livers, probably a secondary effect due to general liver pathology.
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PMID:Cystic fibrosis liver sialyltransferase. 2 13

By means of affinity chromatography on CDP-hexanolamine-agarose, a CMP-N-acetylneuraminate: alpha-N-acetylgalactosaminide alpha 2 leads to 6 sialyltransferase (EC 2.4.99.1) has been purified 117,000-fold to homogeneity from Triton X-100 extracts of porcine submaxillary glands. The enzyme consists of several electrophoretic forms that can be partially resolved by chromatography on Sephadex G-200, the largest of which has a molecular weight of approximately 160,000 as estimated by sodium dodecyl sulfate-gel electrophoresis. Periodate oxidation studies show that the linkage formed by this enzyme with ovine submaxillary asialo-mucin as the acceptor substrate is NeuAc alpha 2 leads to 6GalNAc alpha 1 leads to O-Thr/Ser. On the basis of initial rate studies and the patterns of inhibition observed with alternate acceptor substrates, the transferase is proposed to have either a random equilibrium kinetic mechanism or an ordered steady state mechanism with the acceptor substrate binding first. Among a wide variety of oligosaccharides, glycoproteins, and simple glycosides (including p-nitrophenyl-alpha-N-acetylgalactosaminide), the only acceptor substrates for this enzyme are those glycoproteins containing the structure, R leads to 3GalNAc alpha 1 leads to O-Thr/Ser, where R may be H or a beta-galactoside.
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PMID:Purification to homogeneity and enzymatic characterization of an alpha-N-acetylgalactosaminide alpha 2 leads to 6 sialyltransferase from porcine submaxillary glands. 44 88

Liver microsomal fractions catalyse the transfer of sialic acid from CMP-N-acetyl-neuraminic acid to various exogenous acceptors such as desialylated fetuin, desialylated human Tamm-Horsfall glycoprotein and desialylated bovine submaxillary-gland mucin. An increase in the rate of incorporation of sialic acid into desialylated glycoproteins was found after a lag period (7h) in regenerating liver. The increase was maximum 24h after partial hepatectomy for all acceptors tested. At later times after operation the sialyltransferase activity remained high only for desialylated fetuin. No soluble factors from liver or serum of partially hepatectomized animals influenced the activity of the sialyltransferases bound to the microsomal fraction. The sensitivity of sialyltransferases to activation by Triton X-100, added to the incubation medium, was unchanged in the microsomal preparation from animals 24h after sham operation or partial hepatectomy. The full activity of sialyltransferases towards the various desialylated acceptors showed some differences. Human Tamm-Horsfall glycoprotein was a good acceptor of sialic acid only when desialylated by mild acid hydrolysis. After this treatment, but not after enzymic hydrolysis, a decrease in molecular weight of human Tamm-Horsfall glycoprotein was observed. Further, the sialyltransferase activity as a function of incubation temperature gave different curves according to the acceptor used. The relationship between the biosynthesis of glycoproteins by regenerating liver and the sialyltransferase activity of microsomal fraction after partial hepatectomy is discussed.
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PMID:Sialyltransferase activity in regenerating rat liver. 59 33

The glycosyltransferases controlling the biosynthesis of cell-surface complex carbohydrates transfer glycosyl residues from sugar nucleotides to specific hydroxyl groups of acceptor oligosaccharides. These enzymes represent prime targets for the design of glycosylation inhibitors with the potential to specifically alter the structures of cell-surface glycoconjugates. With the aim of producing such inhibitors, synthetic oligosaccharide substrates were prepared for eight different glycosyltransferases. The enzymes investigated were: A, alpha(1----2, porcine submaxillary gland); B, alpha(1----3/4, Lewis); C, alpha(1----4, mung bean); D, alpha(1----3, Lex)-fucosyltransferases; E, beta(1----4)-galactosyltransferase; F, beta(1----6)-N-acetylglucosaminyltransferase V; G, beta(1----6)-mucin-N-acetylglucosaminyltransferase ("core-2" transferase); and H, alpha(2----3)-sialyltransferase from rat liver. These enzymes all transfer sugar residues from their respective sugar nucleotides (GDP-Fuc, UDP-Gal, UDP-GlcNAc, and CMP-sialic acid) with inversion of configuration at their anomeric centers. The Km values for their synthetic oligosaccharide acceptors were in the range of 0.036-1.3 mM. For each of these eight enzymes, acceptor analogs were next prepared where the hydroxyl group undergoing glycosylation was chemically removed and replaced by hydrogen. The resulting deoxygenated acceptor analogs can no longer be substrates for the corresponding glycosyltransferases and, if still bound by the enzymes, should act as competitive inhibitors. In only four of the eight cases examined (enzymes A, C, F, and G) did the deoxygenated acceptor analogs inhibit their target enzymes, and their Ki values (all competitive) remained in the general range of the corresponding acceptor Km values. No inhibition was observed for the remaining four enzymes even at high concentrations of deoxygenated acceptor analog. For these latter enzymes it is suggested that the reactive acceptor hydroxyl groups are involved in a critical hydrogen bond donor interaction with a basic group on the enzyme which removes the developing proton during the glycosyl transfer reaction. Such groups are proposed to represent logical targets for irreversible covalent inactivation of this class of enzyme.
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PMID:Evaluation of deoxygenated oligosaccharide acceptor analogs as specific inhibitors of glycosyltransferases. 191 26

Sialidase and sialyltransferase activities were studied in JB6 mouse epidermal cells before and after exposure to phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (TPA), which irreversibly induces anchorage-independent growth and tumorigenicity. JB6 cells exhibited sialidase activities toward 4-methylumbelliferyl-alpha-D-N-acetylneuraminic acid (4MU-NeuAc) and gangliosides at pH 4.5 in the particulate fraction but apparently not in the cytosol at pH 4.5 or 6.0. In JB6 cells exposed to TPA and in the anchorage-independent transformants, the sialidase activity toward 4MU-NeuAc was decreased and the activity toward gangliosides was increased compared with those in untreated JB6 cells. Immunological analysis with antisera against membrane-associated sialidases I and II revealed that plasma membrane-associated sialidase I was increased and lysosomal membrane-associated sialidase II was decreased under these conditions. TPA treatment also affected the sialyltransferase activities of JB6 cells: and elevation of the transfer activities toward asialo-orosomucoid and asialo-porcine submaxillary mucin but a reduction of GM3 and GD3 synthase activities were observed on exposure to TPA and in cells transformed by TPA to retain anchorage-independency. These results suggest that an increase in sialic acid bound to glycoproteins and a decrease in that bound to glycolipids may occur in JB6 cells exposed to TPA and in the anchorage-independent transformants.
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PMID:Tumor-promoting phorbol ester induces alterations of sialidase and sialyltransferase activities of JB6 cells. 212 97

We present evidence for the existence in rat brain of several sialyltransferases able to sialylate sequentially asialofetuin. [14C]Sialylated glycans of asialofetuin were analyzed by gel filtration. Three types of [14C]sialylated glycans were synthesized: N-glycans and monosialylated and disialylated O-glycans. The varying effects of N-ethylmaleimide, lysophosphatidylcholine (lysoPtdCho) and trypsin, were helpful in the identification of these different sialyltransferases. One of them, selectively inhibited by N-ethylmaleimide, was identified as the Neu5Ac alpha 2----3Gal beta 1----3GalNAc-R:alpha 2----6 sialyltransferase previously described [Baubichon-Cortay, H., Serres-Guillaumond, M., Louisot, P. and Broquet, P. (1986) Carbohydr. Res. 149, 209-223]. This enzyme was responsible for the synthesis of disialylated O-glycans. LysoPtdCho and trypsin selectively inhibited the enzyme responsible for the synthesis of monosialylated O-glycan. N-ethylmaleimide, lysoPtdCho and trypsin did not inhibit Neu5Ac transfer onto N-glycans, giving evidence for three different molecular species. To identify the enzyme responsible for monosialylated O-glycan synthesis, we used another substrate: Gal beta 1----3GalNAc--protein obtained after galactosylation of desialylated ovine mucin by a GalNAc-R:beta 1----3 galactosyltransferase from porcine submaxillary gland. This acceptor was devoid of N-glycans and of NeuAc in alpha 2----3 linkages on the galactose residue. When using N-ethylmaleimide we obtained the synthesis of only one product, a monosialylated structure. After structural analysis by HPLC on SAX and SiNH2 columns, we identified this product as Neu5Ac alpha 2----3Gal beta 1----3GalNAc. The enzyme leading to synthesis of this monosialylated O-glycan was identified as a Gal beta 1----3GalNAc-R:alpha 2----3 sialyltransferase. When using lysoPtdCho and trypsin, sialylation was completely abolished, although the Neu5Ac alpha 2----3Gal beta 1----3GalNAc-R:alpha 2----6 sialyltransferase was not inhibited. We provided thus evidence for the interpendence between the two enzymes, the alpha 2----3 sialyltransferase regulates the alpha 2----6 sialyltransferase activity since it synthesizes the alpha 2----6 sialyltransferase substrate.
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PMID:Evidence for an O-glycan sialylation system in brain. Characterization of a beta-galactoside alpha 2,3-sialyltransferase from rat brain regulating the expression of an alpha-N-acetylgalactosaminide alpha 2,6-sialyltransferase activity. 247 71

1. Sialyl- and galactosyl-transferase activities were determined in wild type and conA-resistant L6 rat myoblasts with substrates derived from fetuin, alpha 1-acid glycoprotein and bovine submaxillary mucin; fetuin was the best acceptor for both enzyme activities, whereas the mucin did not act as an acceptor. 2. The optimum pH for sialyltransferase was 6.6 in both cell lines. 3. The optimum pH for galactosyltransferase in the wild type cell line was 6.2 which was slightly higher than the value of 5.8 found for the conA-resistant cells. 4. Values for Km for both enzyme activities increased five to ten-fold in the variant cell line with both acceptors. 5. The main sialyltransferase activity was the Gal beta 1----4GlcNAc alpha 2----3sialyltransferase for N-linked chains. The galactosyltransferase was most likely the enzyme that is responsible for the synthesis of the Gal beta 1----4GlcNAc structure.
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PMID:Studies on glycosyltransferases in fusion-defective conA-resistant L6 rat myoblast cell lines. 250 4

Sialyltransferase activity in normal human breast tissue and tumors was investigated with lactose, desialylated fetuin, and bovine submaxillary mucin as the acceptors. While microsomal preparations from the normal tissue showed little or no sialyltransferase activity toward these acceptors, tumors showed elevated enzymic activities. Tween-20 at 0.5% concentrations stimulated sialic acid transfer to all three acceptors. Another nonionic detergent, Triton X-100, stimulated asialo fetuin sialyltransferase activity while inhibiting activity toward asialo BSM and lactose. Interestingly, lysolecithin, a normal cellular constituent which possesses detergent properties also had an effect similar to that of Triton X-100. Thermal denaturation curves of enzymic activity toward asialo BSM, however, resembled those seen with asialo fetuin as the acceptor. Kinetic studies showed that at acceptor concentrations of 500 micrograms each, sialyl transfers to asialo fetuin, asialo BSM, and lactose showed apparent Km values of 50, 60, and 300 microM, respectively. At CMP-sialic acid concentrations of 300 microM, the Km values for the above acceptors were 25, 15, and 5000 microM.
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PMID:Some biochemical properties of human breast tumor sialyltransferase. 258 61

Sialyltransferases responsible for the formation of sugar chains in glycoproteins were studied in rat hepatoma in comparison with rat liver. Hepatoma induced by feeding Wistar rats with 3'-methyl-4-dimethylaminoazobenzene (MeDAB) was more active than Wistar liver in sialylating asialo-orosomucoid, and this was due to an increased activity of Gal(beta 1----4)GlcNAc (alpha 2----6) sialyltransferase, the major sialyltransferase in these tissues. Gal(beta 1----3,4)GlcNAc (alpha 2----3) sialyltransferase and the sialyltransferase acting on asialo-bovine submaxillary mucin were, however, decreased in the hepatoma. A similar pattern of sialyltransferase alterations was observed in regenerating liver and other tumors such as AH-109A hepatoma and Sato lung cancer, both of which had been inoculated into Donryu rats. In contrast to these sialyltransferases, the activities of the sialyltransferases responsible for the formation of gangliosides were markedly different even between Wistar and Donryu livers. When compared with Wistar liver, MeDAB-induced hepatoma was higher in lactosylceramide- and lower in GM3-sialyltransferase activity, but these two activities were both lower in AH-109A compared with Donryu liver.
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PMID:Comparative study of the levels of sialyltransferases responsible for the formation of sugar chains in glycoproteins and gangliosides in rat liver and hepatomas. 313 1

Lymph node (LN) T cells from autoimmune MRL/MpJ-lpr/lpr (lpr) mice and control MRL/MpJ-+/+ (+/+) mice were compared as to their cell surface lectin-binding sites and glycosyltransferase activities. T cells from enlarged LN of lpr mice expressed a higher amount of binding sites for lectins reactive to mucin-type sugar chains than normal +/+ mouse T cells. Correspondingly, glycosyltransferase activities involved in the biosynthesis of mucin-type sugar chains were higher in lpr mouse T cells than in +/+ T cells. The activities of UDP-N-acetylgalactosamine (GalNAc):polypeptide GalNAc transferase and UDP-galactose (Gal):asialo bovine submaxillary mucin (BSM) Gal transferase were found to be elevated. The activity of UDP-Gal:asialo-agalacto transferrin Gal transferase, which is involved in the biosynthesis of complex type sugar chains, was also increased in lpr mice but to a smaller extent than the mucin-type Gal transferase activities. An abnormality in sialyltransferase activity was also found in lpr T cells.
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PMID:Enhancement of the activities of glycosyltransferases involved in the biosynthesis of mucin-type sugar chains in autoimmune MRL lpr/lpr mouse T cells. 313 57


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