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

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

Three enzymatic activities associated with pyrimidine nucleotide biosynthesis were monitored at weekly or bi-weekly intervals during 2-acetylaminofluorene- (0.025% in a Farber Basal Carcinogenic diet) induced hepatocarcinogenesis in the rat. Dihydroorotate dehydrogenase, the fourth of six enzymes in de novo pyrimidine biosynthesis, declined in activity while UDP kinase and CTP synthetase showed sequential increases in activity. The alterations in activity appeared to be cyclic, followed by a full or partial return to control values. Three full cycles were monitored. The first cycle preceded nodule formation. The second cycle accompanied nodule formation and preceded sialoglycoconjugate changes reported previously. The third cycle accompanied the early glycoconjugate changes. The cyclic pattern was reproducible in three separate experiments. In each cycle, the order of events was as follows: decrease in dihydroorotate dehydrogenase, sequential increases in UDP kinase, CTP synthetase and CMPsialic acid synthase, and finally increases in the enzyme lactosylceramide: CMPsialic acid sialyltransferase, lipid-soluble sialic acid and total sialic acid. In livers of animals fed 1.87% of the hepatotoxin, 4-acetamidophenol, no biochemical alterations resembling those induced by 2-acetylaminofluorene were obtained, despite acute centrilobular necrosis of the livers. The findings point to a biochemical cascade beginning with administration of carcinogen and continuing through the development of hyperplastic nodules and of frank carcinomas resulting not from hepatotoxicity but as events associated with the hepatocarcinogenic progression.
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PMID:Cyclic modulation of enzymes of pyrimidine nucleotide biosynthesis precedes sialoglycoconjugate changes during 2-acetylaminofluorene-induced hepatocarcinogenesis in the rat. 633 24

A large-scale production system of cytidine 5'monophospho-N-acetylneuraminic acid (CMP-NeuAc) and sialyloligosaccharides was established by a whole-cell reaction through the combination of recombinant Escherichia coli strains and Corynebacterium ammonia-genes. For the production of CMP-NeuAc, two recombinant E. coli strains were generated that overexpressed the genes of CMP-NeuAc synthetase and CTP synthetase, respectively. C. ammoniagenes contributed to the formation of UTP from orotic acid. CMP-NeuAc was accumulated at 27 mM (17 g/l) after a 27-h reaction starting with orotic acid and N-acetylneuraminic acid. When E. coli cells that overexpressed the alpha-(2-->3)-sialyltransferase gene of Neisseria gonorrhoeae were put into the CMP-NeuAc production system, 3'-sialyllactose was accumulated at 52 mM (33 g/l) after an 11-h reaction starting with orotic acid, N-acetylneuraminic acid, and lactose. Almost no oligosaccharide byproducts other than 3'-sialyllactose were observed after the reaction. The production of 3'-sialyllactose at a 5-l jar fermenter scale was almost the same as that at a beaker scale, which indicated the high potential of the 3'-sialyllactose production on an industrial scale.
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PMID:Large-scale production of CMP-NeuAc and sialylated oligosaccharides through bacterial coupling. 1077 62