The enzymic synthesis of ganglioside: I. Brain uridine diphopphate D‐galactose: N‐acetyl‐galactosaminyl‐galactosyl‐glucosyl‐ceramide galactosyl transferase

Yip, Morris C.M.; Dain, Joel A.

doi:10.1007/bf02533185

Cited by 44 publications

(6 citation statements)

References 22 publications

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“…In the present study we also observed that the concentrations of higher ganglioside homologues with migration of GMl, GDlb, GD16 and GT correlated positively with sensitivity of target cells to NK-cell-mediated lysis. These observations on the presence of asialo G, , G, , GDla, GDlb in NK-sensitive target cells suggest the existence of the alternate pathway for ganglioside biosynthesis (CM + CD + asialo G, + G, + GMl + GDla -+ GDlb + GT) (Handa and Burton, 1969;Yip and Dain, 1969;Yogeeswaran and Stein, 1980). In contrast, NK-insensitive targets lack asialo-G,, suggesting the presence of the classical pathway for the ganglioside biosynthesis (CM GT) which may be operative in these cell lines.…”

Section: Ir; 5 A9ht; 6 Yac-wa9ht; 7mentioning

confidence: 92%

Correlation of glycosphingolipids and sialic acid in YAC‐1 lymphoma variants with their sensitivity to natural killer‐cell‐mediated lysis

Yogeeswaran

Grönberg

Hansson

et al. 1981

Intl Journal of Cancer

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Sialoglycoconjugates and glycosphingolipids were quantitated in a series of variants derived from the YAC-1 lymphoma, known to be highly sensitive to natural killer (NK)-cell-mediated lysis. The variants, which had widely diverging sensitivities to NK cells, were obtained by a number of methods, including selection in the presence of NK cells, antibody to H-2, or antibody to the murine leukemia-virus-induced antigen, and by fusion of sensitive cells with an NK-resistant cell line, A9HT. The sensitivities of these cells to NK-cell-mediated lysis did not correlate with their sensitivities to anti-H-2a cytotoxic T cells. While no correlation could be made between the NK-sensitivity of these variants and their total cellular sialic acid, a statistically significant inverse correlation was observed between the levels of percentage neuraminidase releasable surface sialic acid of total labelled sialyl components and sensitivity to NK cells. This correlation with cell surface sialic acid was observed with either endogenous or lymphocytic choriomeningitis virus-induced activated NK cells as effectors. Neuraminidase treatment of insensitive target cells caused a moderate increase in sensitivity but failed to render the resistant targets as sensitive as YAC-1. Analysis of glycosphingolipids among the variants revealed a strong positive correlation between the total cell neutral glycolipid with chromatographic migration of asialo-GM2 and sensitivity to endogenous or activated NK-cell-mediated lysis. Significant correlations were not found with any other neutral glycolipids. However, ganglioside homologues with chromatographic mobility of GM1, GD1a, GD1b, And GT also showed a positive correlation with both endogenous and activated NK-cell-mediated lysis. The ratio of asialo-GM2 to GM2 had a highly significant positive correlation with sensitivity. These correlative results suggest that asialo-GM2 and certain gangliosides could be involved in binding or lytic events in NK cell:target cell interactions, and that high levels of sialic acid and sialylation on the surface may inhibit and/or modify such interactions. Further studies with these YAC variants should be useful for examining the biochemical bases of target cell-effector cell interactions in the NK-system.

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Section: Ir; 5 A9ht; 6 Yac-wa9ht; 7mentioning

confidence: 92%

Correlation of glycosphingolipids and sialic acid in YAC‐1 lymphoma variants with their sensitivity to natural killer‐cell‐mediated lysis

Yogeeswaran

Grönberg

Hansson

et al. 1981

Intl Journal of Cancer

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“…The gangliosides are membrane constituents; however, very few membrane models have been proposed in which these compounds are considered (Lehninger, 1968) and we know of no report in which their synthesis is studied as part of a growing or turning-over membrane. A pathway for the biosynthesis of the carbohydrate chain of the gangliosides was proposed by Kaufman, Basu & Roseman (1966) and a different one by Kanfer, Blacklow, Warren & Brady (1964), Yip & Dain (1969) and Handa & Burton (1969). These pathways have been worked out from reactions occurring between water-soluble donors of glycosyl groups and lipid-soluble acceptors, catalysed by particulate preparations in a medium containing detergents which presumably altered the structures of the membranes.…”

mentioning

confidence: 99%

The biosynthesis of gangliosides. The incorporation of galactose, N-acetylgalactosamine and N-acetylneuraminic acid into endogenous acceptors of subcellular particles from rat brain in vitro

Arce¹,

Maccioni²,

Caputto³

1971

Biochemical Journal

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Gangliosides bound to subcellular particles from rat brain were labelled by incubation of the particles (i) with CMP-N[(3)H]-acetylneuraminic acid and (ii) simultaneously, with CMP-N[(3)H]-acetylneuraminic acid and UDP-N-acetyl-[(14)C(1)]galactosamine or with CMP-N[(3)H]-acetylneuraminic acid and UDP-[U-(14)C]-galactose. Analysis of the labelled gangliosides showed that in (i), (a) the labelling was mostly in the neuraminidase-labile sialyl groups, (b) rigid relationships exist between the enzymes and the sialyl acceptors; the enzymes are not free to interact with all the specific substrates present in the preparation and (c) the precursor of the trisialoganglioside was the major disialoganglioside with a sialyl 2-->8 sialyl group. In (ii), (a) precursor-product relationships between the main pools of each ganglioside apparently do not exist, (b) for the labelling of Tay-Sachs ganglioside the amount formed from hematoside was at least 2.5 times that from aminoglycolipid and (c) the major monosialoganglioside was the precursor for the major disialoganglioside with a sialyl 2-->8 sialyl group.

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“…Asialo-GM 1 is then catalyzed to GMlb by a sialyltransferase. The enzymes involved in the formation of asialo-GM2 and asialo-GM1 were present in the nonadehsive rat ascites hepatoma cells (13) and in brain tissue (7,14). Therefore, the brain tissue and the nonadhesive rat ascites hepatoma ceils have similar enzymic components for the biosynthesis of GM 1 b in vivo.…”

Section: Discussionmentioning

confidence: 97%

“…Although the natural occurrence of this novel monosialoganglioside has yet to be proven in brain tissue, the dramatic accumulation of its proposed precursor, asialo-GM1, from patients afflicted with generalized gangliosidoses (10) and in nonadhesive rat ascites hepatoma cells (11) suggests that the synthesis of GMlb in vivo is possible. A most recent demonstration of the natural occurrence of GM 1 b in nonadhesive rat ascites hepatoma cells (12) has added considerable weight to the in vivo operation of the asialoglycolipid pathway for ganglioside biosynthesis originally proposed by Yip and Dain (7). The asialoglycolipid pathway involves the stepwise synthesis of the glycolipid precursors, dihexosylceramide (GL-2a), asialo-GM2 and asialo-GM1, from glucosylceramide by 3 glycosyltransferases.…”

Section: Discussionmentioning

confidence: 99%

“…The significance of this enzymic reaction is discussed in relation to the in vivo operation of the asialoglycolipid pathway for the synthesis of ganglioside. (5) with the modification of Arce et al (6); the asialo-GM1 was prepared by acid hydrolysis (0.1 N HC1) of bovine brain gangliosides for 1 hr at 100 C, and was purified by preparative thin layer chromatography (TLC) (7). Nonradioactive GM 1 b was biosynthesized in large-scale preparation as described previously (4).…”

Section: Introductionmentioning

confidence: 99%

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The enzymic synthesis of GM1b: rat‐brain CMP‐N‐Acetylneuraminic acid: Asialo‐GM1 sialyltransferase

Yip¹,

Nguyen²

1981

Lipids

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An enzyme which catalyzes the transfer of N-acetylneuraminic acid (NeuNAc) to a tetrahexosylceramide (asialo-GM1) in young rat brain is described. The enzymic product is a new monosialoganglioside containing a neuraminidase-labile neuraminic acid, GM1b. The activity of this sialyltransferase is higher in fetal and young rat brains. The enzyme exhibits a pH optimum of 6.5 in cacodylate buffer. The incorporation of radioactivity into GM1b is stimulated in the presence of asialo-GM1 and CMP-NeuNAc and is dependent on the quantity added. The detergent mixture, Tween 80 and CF54, is required for optimal activity. Recent demonstration of the natural occurrence of GM1b in the free cell types of rat ascites hepatopa cells suggests a functional importance of this CMP-Neu-NAc:asialo-GM1 sialyltransferase in the in vivo formation of this novel monosialoganglioside.

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The enzymic synthesis of ganglioside: I. Brain uridine diphopphate D‐galactose: N‐acetyl‐galactosaminyl‐galactosyl‐glucosyl‐ceramide galactosyl transferase

Cited by 44 publications

References 22 publications

Correlation of glycosphingolipids and sialic acid in YAC‐1 lymphoma variants with their sensitivity to natural killer‐cell‐mediated lysis

Correlation of glycosphingolipids and sialic acid in YAC‐1 lymphoma variants with their sensitivity to natural killer‐cell‐mediated lysis

The biosynthesis of gangliosides. The incorporation of galactose, N-acetylgalactosamine and N-acetylneuraminic acid into endogenous acceptors of subcellular particles from rat brain in vitro

The enzymic synthesis of GM1b: rat‐brain CMP‐N‐Acetylneuraminic acid: Asialo‐GM1 sialyltransferase

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