Inhibition of CMP-N-Acetylneuraminic Acid: Lactosylceramide Sialyltransferase by Nucleotides, Nucleotide Sugars and Nucleotide Dialdehydes

Cambron, Laurence D.; Leskawa, Kenneth C.

doi:10.1006/bbrc.1993.1664

Cited by 13 publications

(4 citation statements)

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“…1A), compared to control assays, indicating that incorporation of sialic acid had occurred. This incorporation was inhibited by a cytidine nucleotide, CTP, one of the most suitable sialyltransferase inhibitors [19,20], substantiating the fact that the assay was indeed detecting genuine sialyltransferase activity. Concordantly, in assays performed at 4 • C sialic acid incorporation was negligible.…”

Section: Evidence Of Non-intracellular Sialyltransferase Activity In mentioning

confidence: 52%

“…Through the use of a very sensitive fluorescence-based sialyltransferase assay, we were able to determine cell surface sialylation by flow cytometry and microscopy, and thus prove that mo-DC exhibit a surface enzymatic activity that rapidly restores its sialic acid content and is inhibited by the sialyltransferase inhibitor, CTP [19,20]. In addition, given the important DC functions which are modulated by sialylation [9], we attempted to address different functional aspects by analysing whether surface sialyltransferase activity is influenced by maturation and if this activity affects mo-DC capacity for endocytosis.…”

Section: Introductionmentioning

confidence: 99%

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Human dendritic cells contain cell surface sialyltransferase activity

et al. 2010

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Section: Evidence Of Non-intracellular Sialyltransferase Activity In mentioning

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Human dendritic cells contain cell surface sialyltransferase activity

et al. 2010

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“…Lumenal conversion to UMP of the UDP resulting from the transfer of the galactose residue to an acceptor is performed by UDPpyrophosphatase, and this enzyme was localized to the trans Golgi and the TGN by electron microscopy (61,80). Absence of this hydrolase in the early Golgi again is in line with the presence of SAT-I in the late part of the organelle, because UDP is known to inhibit the activity of this sialyltransferase (81).…”

Section: Discussionmentioning

confidence: 92%

Functional Organization of the Golgi Apparatus in Glycosphingolipid Biosynthesis

Lannert¹,

Gorgas²,

Meißner³

et al. 1998

Journal of Biological Chemistry

119

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Biosynthesis of plasma membrane sphingolipids involves the coordinate action of enzymes localized to individual compartments of the biosynthetic secretory pathway of proteins. These stations include the endoplasmic reticulum and the Golgi apparatus. Although a precise localization of all the enzymes that synthesize glycosphingolipids has not been achieved to date, it is assumed that the sequence of events in glycosphingolipid biosynthesis resembles that in glycoprotein biosynthesis, i.e. that early reactions occur in early stations (endoplasmic reticulum and cis/medial Golgi) of the pathway, and late reactions occur in late stations (trans Golgi/trans Golgi network).Using truncated analogues of ceramide and glucosylceramide that allow measurement of enzyme activities in intact membrane fractions, we have reinvestigated the localization of individual enzymes involved in glycosphingolipid biosynthesis and for the first time studied the localization of lactosylceramide synthase after partial separation of Golgi membranes as previously described (Trinchera, M., and Ghidoni, R. (1989) J. Biol. Chem. 264, 15766 -15769). Here, we show that the reactions involved in higher glycosphingolipid biosynthesis, including lactosylceramide synthesis, all reside in the lumen of the late Golgi compartments from rat liver.

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“…Discrimination against UMP may also help to reduce the lumenal concentration of CMP, thereby minimizing the amount of inhibition of sialyltransferases by CMP. Previous studies of various sialyltransferases have shown that, in some cases, elevated CMP concentrations significantly inhibit these enzymes ( − ). For example, in assays containing 1 mM CMP-sialic acid, 1 mM CMP inhibited G D3 synthase by approximately 61% and G D1a synthase by only approximately 21% ().…”

Section: Discussionmentioning

confidence: 99%

Inhibition of CMP-Sialic Acid Transport into Golgi Vesicles by Nucleoside Monophosphates

et al. 2001

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We examined the interactions of nucleotides with the CMP-sialic acid transporter in order to better understand which features play a role in binding and to investigate the relationship between binding and subsequent transport. With respect to the sugar, the transporter requires a complete ribose ring for tight binding, and the 2'-ara hydrogen makes an important contact. The enzyme exhibits little specificity with respect to the 2'- and 3'-hydroxyls, as it tolerated substitutions ranging from fluorine to an azido group. In the base, the C4 amine and C2 carbonyl groups make important contacts, while the N3 nitrogen does not. However, adding a methyl group to N3 dramatically reduced binding, indicating that mass at this position sterically hinders binding. Adding a group at C5 had either no effect or slightly enhanced binding. To determine if the transporter recognizes these CMP analogues as substrates, we assayed them for their ability to trans stimulate CMP-sialic acid import. These data suggest that the enzyme transports a wide variety of NMPs, and the rate of transport is inversely proportional to the K(I) of the analogue. The importance of our findings for understanding the specificities of the different nucleotide-sugar tranlocators and the design of novel glycosylation inhibitors are discussed.

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Inhibition of CMP-N-Acetylneuraminic Acid: Lactosylceramide Sialyltransferase by Nucleotides, Nucleotide Sugars and Nucleotide Dialdehydes

Cited by 13 publications

References 0 publications

Human dendritic cells contain cell surface sialyltransferase activity

Human dendritic cells contain cell surface sialyltransferase activity

Functional Organization of the Golgi Apparatus in Glycosphingolipid Biosynthesis

Inhibition of CMP-Sialic Acid Transport into Golgi Vesicles by Nucleoside Monophosphates

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