scholarly journals Incorporation and metabolism of exogenous GM1 ganglioside in rat liver

1986 ◽  
Vol 237 (1) ◽  
pp. 147-155 ◽  
Author(s):  
R Ghidoni ◽  
M Trinchera ◽  
B Venerando ◽  
A Fiorilli ◽  
S Sonnino ◽  
...  
Keyword(s):  
Rat Liver ◽  
Degradation Process ◽  
Major Product ◽  
The Other ◽  
Gm1 Ganglioside ◽  
Lysosomal Fraction ◽  
Long Chain Base ◽  
Terminal Galactose ◽  
Subcellular Level ◽  
Long Chain

The pathways of metabolic processing of exogenously administered GM1 ganglioside in rat liver was investigated at the subcellular level. The GM1 used was 3H-labelled at the level of long-chain base ([Sph(sphingosine)-3H]GM1) or of terminal galactose ([Gal-3H]GM1). The following radioactive compounds, derived from exogenous GM1, were isolated and chemically characterized: gangliosides GM2, GM3, GD1a and GD1b (nomenclature of Svennerholm [(1964) J. Lipid Res. 5, 145-155] and IUPAC-IUB Recommendations [(1977) Lipids 12, 455-468]); lactosylceramide, glucosylceramide and ceramide; sphingomyelin. GM2, GM3, lactosylceramide, glucosylceramide and ceramide, relatively more abundant shortly after GM1 administration, were mainly present in the lysosomal fraction and reflected the occurrence of a degradation process. 3H2O was also produced in relevant amounts, indicating complete degradation of GM1, although no free long-chain bases could be detected. GD1a and GD1b, relatively more abundant later on after administration, were preponderant in the Golgi-apparatus fraction and originated from a biosynthetic process. More GD1a was produced starting from [Sph-3H]GM1 than from [Gal-3H]GM1, and radioactive GD1b was present only after [Sph-3H]GM1 injection. This indicates the use of two biosynthetic routes, one starting from a by-product of GM1 degradation, the other implicating direct sialylation of GM1. Both routes were used to produce GD1a, but only the first one for producing GD1b. Sphingomyelin was the major product of GM1 processing, especially at the longer times after injection, and arose from a by-product of GM1 degradation, most likely ceramide.

scholarly journals Recycling of glucosylceramide and sphingosine for the biosynthesis of gangliosides and sphingomyelin in rat liver

1990 ◽  
Vol 270 (3) ◽  
pp. 815-820 ◽  
Author(s):  
M Trinchera ◽  
R Ghidoni ◽  
S Sonnino ◽  
G Tettamanti
Keyword(s):  
Fatty Acid ◽  
Intravenous Injection ◽  
Rat Liver ◽  
Sugar Residue ◽  
Gm1 Ganglioside ◽  
Chain Base ◽  
Neutral Glycosphingolipids ◽  
Long Chain Base ◽  
Ganglioside Biosynthesis ◽  
Long Chain

It was previously shown that sphingomyelin and gangliosides can be biosynthesized starting from sphingosine or sphingosine-containing fragments which originated in the course of GM1 ganglioside catabolism. In the present paper we investigated which fragments were specifically re-used for sphingomyelin and ganglioside biosynthesis in rat liver. At 30 h after intravenous injection of GM1 labelled at the level of the fatty acid ([stearoyl-14C]GM1) or of the sphingosine ([Sph-3H]) moiety, it was observed that radioactive sphingomyelin was formed almost exclusively after the sphingosine-labelled-GM1 administration. This permitted the recognition of sphingosine as the metabolite re-used for sphingomyelin biosynthesis. Conversely, gangliosides more complex than GM1 were similarly radiolabelled after the two treatments, thus ruling out sphingosine re-utilization for ganglioside biosynthesis. For the identification of the lipid fragment re-used for ganglioside biosynthesis, we administered to rats neutral glycosphingolipids (galactosylceramide, glucosylceramide and lactosylceramide) each radiolabelled in the sphingosine moiety or in the terminal sugar residue. Thereafter we compared the formation of radiolabelled gangliosides in the liver with respect to the species administered and the label location. After galactosylceramide was injected, no radiolabelled gangliosides were formed. After the administration of differently labelled glucosylceramide, radiolabelled gangliosides were formed, regardless of the position of the label. After lactosylceramide administration, the ganglioside fraction became more radioactive when the long-chain-base-labelled precursors were used. These results suggest that glucosylceramide, derived from glycosphingolipid and ganglioside catabolism, is recycled for ganglioside biosynthesis.

scholarly journals Subcellular distribution and characteristics of trihydroxycoprostanoyl-CoA synthetase in rat liver

1989 ◽  
Vol 257 (1) ◽  
pp. 221-229 ◽  
Author(s):  
L Schepers ◽  
M Casteels ◽  
K Verheyden ◽  
G Parmentier ◽  
S Asselberghs ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cholic Acid ◽  
Rat Liver ◽  
Subcellular Distribution ◽  
The Other ◽  
Acid Activation ◽  
Long Chain Fatty Acids ◽  
Microsomal Membranes ◽  
Triton X ◽  
Long Chain

The subcellular distribution and characteristics of trihydroxycoprostanoyl-CoA synthetase were studied in rat liver and were compared with those of palmitoyl-CoA synthetase and choloyl-CoA synthetase. Trihydroxycoprostanoyl-CoA synthetase and choloyl-CoA synthetase were localized almost completely in the endoplasmic reticulum. A quantitatively insignificant part of trihydroxycoprostanoyl-CoA synthetase was perhaps present in mitochondria. Peroxisomes, which convert trihydroxycoprostanoyl-CoA into choloyl-CoA, were devoid of trihydroxycoprostanoyl-CoA synthetase. As already known, palmitoyl-CoA synthetase was distributed among mitochondria, peroxisomes and endoplasmic reticulum. Substrate- and cofactor- (ATP, CoASH) dependence of the three synthesis activities were also studied. Cholic acid and trihydroxycoprostanic acid did not inhibit palmitoyl-CoA synthetase; palmitate inhibited the other synthetases non-competitively. Likewise, cholic acid inhibited trihydroxycoprostanic acid activation non-competitively and vice versa. The pH curves of the synthetases did not coincide. Triton X-100 affected the activity of each of the synthetases differently. Trihydroxycoprostanoyl-CoA synthetase was less sensitive towards inhibition by pyrophosphate than choloyl-CoA synthetase. The synthetases could not be solubilized from microsomal membranes by treatment with 1 M-NaCl, but could be solubilized with Triton X-100 or Triton X-100 plus NaCl. The detergent-solubilized trihydroxycoprostanoyl-CoA synthetase could be separated from the solubilized choloyl-CoA synthetase and palmitoyl-CoA synthetase by affinity chromatograpy on Sepharose to which trihydroxycoprostanic acid was bound. Choloyl-CoA synthetase and trihydroxycoprostanoyl-CoA synthetase could not be detected in homogenates from kidney or intestinal mucosa. The results indicate that long-chain fatty acids, cholic acid and trihydroxycoprostanic acid are activated by three separate enzymes.

Occurrence of ceramides and neutral glycolipids with unusual long-chain base composition in purified rat liver mitochondria

FEBS Letters ◽  
2001 ◽  
Vol 488 (3) ◽  
pp. 160-164 ◽  
Author(s):  
D Ardail ◽  
I Popa ◽  
K Alcantara ◽  
A Pons ◽  
J.P Zanetta ◽  
...  
Keyword(s):  
Rat Liver ◽  
Base Composition ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Chain Base ◽  
Long Chain Base ◽  
Long Chain

scholarly journals Studies of the ethylation of rat liver transfer ribonucleic acid after administration of l-ethionine

1972 ◽  
Vol 128 (1) ◽  
pp. 59-68 ◽  
Author(s):  
A. E. Pegg
Keyword(s):  
Rat Liver ◽  
Ribonucleic Acid ◽  
Major Part ◽  
Actinomycin D ◽  
Major Product ◽  
The Other ◽  
Methyl Donor ◽  
Principal Product

1. The ethylated nucleosides present in tRNA isolated from the livers of rats treated with 0.5g of l-ethionine/kg body wt. were investigated. Evidence that this tRNA contained N2-ethylguanine, N2N2-diethylguanine, N2-ethyl-N2-methylguanine, 7-ethylguanine, two ethylated pyrimidines and ethylated ribose groups was obtained. 2. Ethylation of bacterial tRNA was catalysed by extracts containing tRNA methylases prepared from rat liver by using S-adenosyl-l-ethionine as an ethyl donor, but the rate of ethylation was 20 times less than the rate of methylation with S-adenosyl-l-methionine as a methyl donor. 3. The principal product of such ethylation in vitro was N2-ethylguanine and traces of the other ethylated guanines and pyrimidines found in tRNA isolated from rats treated with ethionine in vivo were also found. 1-Ethyladenine was not formed, although 1-methyl-adenine is a major product of methylation of bacterial tRNA by these extracts, and 1-ethyladenine was not present in the rat liver tRNA isolated from ethionine-treated animals. 4. After injection of actinomycin D (15mg/kg body wt.) or l-methionine (1.0g/kg body wt.) before the ethionine, ethylation of tRNA was diminished by about 80% but not completely abolished. Administration of 1-aminocyclopentanecarboxylic acid (2.5g/kg body wt.) to inhibit the formation of S-adenosyl-l-ethionine inhibited ethylation of tRNA by 44%. 5. These results suggest that not all of the ethylation of tRNA that occurs in the livers of rats treated with ethionine is mediated by the action of tRNA methylases acting with S-adenosyl-l-ethionine as a substrate, but that this pathway does occur and accounts for a major part of the observed ethylation. 6. The results are discussed with reference to ethionine-induced hepatocarcinogenesis.

scholarly journals Cyclic AMP accumulation in HeLa cells induced by cholera toxin. Involvement of the ceramide moiety of GM1 ganglioside

1990 ◽  
Vol 271 (1) ◽  
pp. 107-111 ◽  
Author(s):  
M Masserini ◽  
P Palestini ◽  
M Pitto ◽  
V Chigorno ◽  
M Tomasi ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Cholera Toxin ◽  
Molecular Species ◽  
Hela Cells ◽  
Gm1 Ganglioside ◽  
Cyclic Amp Accumulation ◽  
Long Chain Base ◽  
Ganglioside Species ◽  
Long Chain ◽  
Ceramide Moiety

The influence of ceramide composition on the rate of GM1 association to HeLa cells has been investigated by incubating the cells in the presence of either native ganglioside or molecular species carrying highly homogeneous long chain base moieties, fractionated from native GM1. The GM1 ganglioside species carrying the unsaturated C18 long chain base moiety proved to have the fastest rate of association, whereas the saturated species carrying 20 carbon atoms had the slowest rate. After having increased the GM1 cell content (65-fold) by incubation with the various ganglioside species, the cells were incubated with cholera toxin and the time course of cyclic AMP accumulation was monitored. Remarkable differences among cells enriched with the various molecular species were found in the duration of the lag time preceding the accumulation of cyclic AMP, the shortest being displayed by the unsaturated C18 species. Moreover, the amount of cyclic AMP accumulated after a given time of incubation with cholera toxin was significantly higher when the C18:1-GM1 species was present than with native GM1. Fluorescence anisotropy experiments, carried out using the probe 1,3-diphenylhexatriene, show that the GM1 ganglioside ceramide moiety was also modifying the cell membrane fluidity of the host.

scholarly journals Preparation of GM1 ganglioside molecular species having homogeneous fatty acid and long chain base moieties.

1985 ◽  
Vol 26 (2) ◽  
pp. 248-257
Author(s):  
S Sonnino ◽  
G Kirschner ◽  
R Ghidoni ◽  
D Acquotti ◽  
G Tettamanti
Keyword(s):  
Fatty Acid ◽  
Molecular Species ◽  
Gm1 Ganglioside ◽  
Chain Base ◽  
Long Chain Base ◽  
Long Chain

METABOLISM OF 17α-HYDROXYPROGESTERONE-4-14C-17α-CAPROATE BY HOMOGENATES OF RAT LIVER AND HUMAN PLACENTA

1961 ◽  
Vol 36 (4) ◽  
pp. 511-519 ◽  
Author(s):  
Margaret Wiener ◽  
Charles I. Lupa ◽  
E. Jürgen Plotz
Keyword(s):  
Rat Liver ◽  
Human Placenta ◽  
Steric Hindrance ◽  
Placental Tissue ◽  
Caproic Acid ◽  
Major Product ◽  
Side Chain ◽  
Anaerobic Conditions ◽  
Prolonged Action ◽  
Long Acting

ABSTRACT 17α-hydroxyprogesterone-4-14C-17α-caproate (HPC), a long-acting progestational agent, was incubated with homogenates of rat liver and human placenta. The rat liver was found to reduce Ring A of HPC under anaerobic conditions to form allopregnane-3β,17α-diol-20-one-17α-caproate and pregnane-3β,17α-diol-20-one-17α-caproate, the allopregnane isomer being the major product. The caproic acid ester was neither removed nor altered during the incubation. Placental tissue did not attack HPC under conditions where the 20-ketone of progesterone was reduced. It is postulated that this absence of attack on the side chain is due to steric hindrance from the caproate ester, and that this may account for the prolonged action of HPC.

BIOSYNTHESE DE LA TRANSCORTINE

1969 ◽  
Vol 62 (3) ◽  
pp. 468-476 ◽  
Author(s):  
Jeanine Guidollet ◽  
Pierre Louisot
Keyword(s):  
Biological Activity ◽  
Rat Liver ◽  
Liver Cell ◽  
Binding Activity ◽  
Subcellular Level

ABSTRACT Corticosteroid-binding activity (transcortin) was investigated at the subcellular level of the rat liver cell: it was located exclusively in the cell sap, and not on the ribosomes or membranes. Oestrogens were found to increase the biological activity of this glycoprotein (corticosterone binding) in the plasma and in the cell sap. The isotopic activity of the glucidic fragments of glycoprotein (after incorporation of 14C-D-glucosamine), however, remained constant or decreased in the specific subcellular sites at which they were incorporated (membranes and cell sap). This absence of correlation between these two results is not in agreement with an induction of transcortin synthesis by oestrogens, but in favour of an activation of normally masked molecular sites.

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