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Gangliosides do not affect ABC transporter function in human neuroblastoma cells.

Previous studies have indicated a role for glucosylceramide synthase (GCS) in multidrug resistance (MDR), either related to turnover of ceramide (Cer) or generation of gangliosides, which modulate apoptosis and/or the activity of ABC transporters. This study challenges the hypothesis that gangliosides modulate the activity of ABC transporters and was performed in two human neuroblastoma cell lines, expressing either functional P-glycoprotein (Pgp) or multidrug resistance-related protein 1 (MRP1). Two inhibitors of GCS, D,L-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol (t-PPPP) and N-butyldeoxynojirimycin (NB-dNJ), very efficiently depleted ganglioside content in two human neuroblastoma cell lines. This was established by three different assays: equilibrium radiolabeling, cholera toxin binding, and mass analysis. Fluorescence-activated cell sorting (FACS) analysis showed that ganglioside depletion only slightly and in the opposite direction affected Pgp- and MRP1-mediated efflux activity. Moreover, both effects were marginal compared with those of well-established inhibitors of either MRP1 (i.e., MK571) or Pgp (i.e., GF120918). t-PPPP slightly enhanced cellular sensitivity to vincristine, as determined by 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyl tetrazolium bromide analysis, in both neuroblastoma cell lines, whereas NB-dNJ was without effect. MRP1 expression and its localization in detergent-resistant membranes were not affected by ganglioside depletion. Together, these results show that gangliosides are not relevant to ABC transporter-mediated MDR in neuroblastoma cells.

1-Deoxynojirimycin↗

Bilirubin interaction with ganglioside: possible mechanism in kernicterus.

Reaction of bilirubin with increasing amounts of ganglioside purified from neonatal brain significantly alters the spectral absorption of bilirubin in proportion to the quantity of ganglioside added. Increments in absorbance occur at 353 nm with a prompt but transient increase at 486 nm. A decrease in absorbance occurs which is most marked at 447 nm. When gangliosides are added to bilirubin (9.1 mug/ml or 0.016 muM/ml), the decrease in absorbance is essentially linear up to the highest concentration of purified ganglioside tested (182 mug/ml or 0.097 muM/ml), which represents a molar ratio of 6.1:1. The asymptotic nature of the bilirubin-ganglioside reaction as measured by the decrease in absorbance with time suggests a stoichiometric relationship between the two substances. An isosbestic point was demonstrated at 405 nm. Observations reported here suggest bilirubin reaction with ganglioside is at least a two-step process.

Bilirubin↗

Hepatic ganglioside abnormalities in a patient with familial erythrophagocytic lymphohistiocytosis.

Familial erythrophagocytic lymphohistiocytosis (FEL) is an autosomal recessive disease of unknown pathogenesis. Because of evidence of increased circulating and hepatic lipids in FEL, we performed a comprehensive analysis of the hepatic lipids of a patient with this disease. In contrast to normal qualitative characteristics and to normal or only mildly elevated concentrations of total lipids, neutral lipids, phospholipids, and neutral glycosphingolipids, this study reports a significant elevation of acidic glycosphingolipids, gangliosides (387 versus 147 nmole lipid-bound sialic acid/g wet weight, patient versus control). This quantitative abnormality was unusual in that it included disproportionately increased concentrations of most of the minor hepatic ganglioside species rather than either a marked increase in one single or a generalized nonspecific increase in all gangliosides, which is characteristic of known disorders exhibiting hepatic ganglioside storage. Activities of the hepatic lysosomal glycosylhydrolases which are important in ganglioside metabolism were therefore assessed by using artificial substrates. Of the enzymes tested, beta-galactosidase activity alone was remarkable, being moderately reduced (33% of that of the normal liver); no biochemical explanation for the reduction was found. The findings suggest FEL may be associated with a unique quantitative and qualitative abnormality in hepatic gangliosides, the cause of which remains to be elucidated.

Child, Preschool↗

The GM2-1 ganglioside islet autoantigen in insulin-dependent diabetes mellitus is expressed in secretory granules and is not beta-cell specific.

The pancreatic islet monosialo-ganglioside (GM2-1), an autoantigen in insulin-dependent diabetes mellitus (IDDM) recently shown to be the target of autoantibodies associated with diabetes development in relatives of IDDM patients, is islet specific within the pancreas, and its expression is metabolically regulatable. In the present study we sought to establish 1) whether GM2-1 is beta-cell specific, and 2) its intracellular localization. To this end, we analyzed the pattern of ganglioside expression in highly purified beta- and non-beta-cells isolated from rat islets. In addition, ganglioside levels were determined in subcellular fractions of a rat beta-cell line (INS). No qualitative or quantitative difference was found in the pattern of ganglioside expression between beta and non-beta rat islet cells, with GM3, GM2-1, and GD3 gangliosides expressed in both cell populations. Within INS cells, GM2-1 ganglioside was expressed in the fraction containing secretory granules and, to a lesser extent, in plasma membranes; GM3 was expressed in secretory granules, whereas GD3 was found only in plasma membranes. These data indicate that the GM2-1 autoantigen is not beta-cell specific within the islets, in accordance with the observation that this molecule is a target of islet cell autoantibodies that bind to the whole pancreatic islet. Interestingly, this autoantigen is present in secretory granules similarly to other autoantigens in IDDM (insulin, carboxypeptidase H, 38-kDa protein, etc.), suggesting that the autoimmunity to the components of this organelle may be central to the pathogenesis of the disease.

Animals↗

Ganglioside composition and its relation to clinical data in brain tumors.

The ganglioside composition of 15 cases of meningioma, 15 cases of astrocytoma, 5 cases of neurinoma, 4 cases of ependymoma, 3 cases of metastatic brain tumor and 1 case each of mixed glioma, oligodendroglioma, medulloblastoma, embryonal carcinoma, and cultured glioma cell line were analyzed by thin-layer chromatography. The GM2, GD3, and GD2 content of the tumors was determined using specific monoclonal antibodies (MAb). Cases were grouped according to the difference in ganglioside pattern and various clinical features. In meningiomas and astrocytomas, GM3 and GD3 were the major gangliosides. The tumor content of the rather simple gangliosides (GM3, GM2, GD3, GD2) increased or was almost equal to that of normal tissue (leptomeninges tissue in the case of meningiomas, and brain tissue in the case of astrocytomas), while the tumor content of complex gangliosides (GM1, GD1a, GT1a, GT1b) decreased as compared with normal tissue. The GM3 content of meningiomas increased in middle-aged patients, who comprised the majority of the patients with these tumors. The GD2 content decreased in middle-aged patients with initial symptoms of meningioma within a year. The GM3 content of astrocytomas decreased in patients who underwent radiotherapy. The amount of GM3 and GD3 increased in small tumors. GM3 may be related to the early proliferative stage. The ganglioside patterns of brain tumors are shown in this study to differ according to clinical features and also to be changeable in their clinical courses.

Aging↗

Effect of gangliosides on murine megakaryocytopoiesis in a liquid culture system.

Bovine brain gangliosides were applied to primary cultures of murine bone marrow cells to examine the role of gangliosides in development of megakaryocytes. Megakaryocytes in the cultures were detected by staining for a cytoplasmic enzyme, acetylcholinesterase, and divided into two types, 1) immature megakaryocytes which were stained less intensely, and 2) mature ones which were stained intensely. A medium containing total ganglioside fraction from bovine brain increased the number of both immature and mature megakaryocytes in the presence of pokeweed mitogen-stimulated murine spleen cell conditioned medium. Between the two cell types, the number of the mature cells was more significantly increased than the immature cells. The ganglioside GD1a could substitute for the total ganglioside mixture. The results suggested that bovine brain gangliosides potentiated both megakaryocytic proliferation and maturation in vitro.

Acetylcholinesterase↗

[Molecular diversity of brain ganglioside and its biological significance].

Gangliosides are sialic acid containing glycosphingolipids found in highest concentrations in central nervous tissues (CNS). More than 100 species of gangliosides including extremely minor components exist in CNS tissues. We have developed a new method using Q-Sepharose to efficiently purify them from complex mixtures of bovine brain gangliosides. Among the isolated gangliosides a unique new series of gangliosides was shown to exist in the polysialoganglioside fraction. They possessed N-acetylneuraminic acid attached to N-acetylgalactosamine in alpha 2-6 linkage. The immunohistochemical staining of human and rat brains with specific monoclonal antibody to the gangliosides showed that they are stained intensely the neuropile of dorsal horn on spinal cord, being presumably expressed on the cholinergic nerve terminals. On the basis of these observations, extremely minor species may play significant roles in CNS. The present data also indicated that brain tissues contain a new type of alpha 2-6 sialytransferase to act on GalNAc in the gangliotetraose structure.

Animals↗

Substrate specificity and inhibitor studies of a membrane-bound ganglioside sialidase isolated from human brain tissue.

A ganglioside-specific sialidase that controls cellular functions such as growth, differentiation, and adhesion has been observed in a variety of cells, but its characterization proved difficult due to firm membrane attachment and lability of the purified enzyme. Here we report on the specificity toward gangliosides and susceptibility to certain inhibitors of a ganglioside sialidase solubilized and purified 5100-fold from human brain. The sialidase removed terminal sialic acids from gangliosides GM3, GM4, GD3, GD2, GD1 a, GD1 b, GT1 b and GQ1 b, but was inactive toward gangliosides with sialic acid in a branching position (as in GM1 and GM2). Lyso-GM3 and -GD1a were good substrates, too, whereas O-acetylation of the sialic acid as in 9-O-acetyl-GD3 caused strongly reduced cleavage. The new influenza virus drug 4-guanidino-2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Zanamivir) exhibited an IC50 value of about 7 x 10(-5) M that was in the range of the 'classical' sialidase inhibitor 2-deoxy-2,3-dehydro-N-acetylneuraminic acid; the bacterial sialidase inhibitor 4-nitrophenyloxamic acid, however, was ineffective. The glycosaminoglycans heparan sulfate, heparin, chondroitin sulfates A and B, as well as dextran sulfate and suramin, were all strongly inhibitory, suggesting that glycosaminoglycans present on the cell surface or in the extracellular matrix may influence the ability of the sialidase to alter the ganglioside composition of the membrane.

Antibody Specificity↗

The influence of sex steroid hormones on ganglioside biosynthesis in rat kidney.

Castrated male rats were subcutaneously injected testosterone (5 and 10 mg) or a mixture of beta-estradiol and progesterone (1 microg + 2 mg), to determine whether sex steroid hormones (testosterone, beta-estradiol, progesterone) might affect the content of sialoglycoproteins, the content and pattern of lipid-bound sialic acid, and the activities of sialyltransferase (SAT) I and SAT II in the Golgi-rich membrane fraction isolated from rat kidney. During four days testosterone did not affect significantly the content of proteins, sialoglycoproteins and total gangliosides, but increased the content of b-series gangliosides from 0.05 +/- 0.006 (untreated animals injected subcutaneously with 0.1 ml DMSO for four days) to 0.16 +/- 0.02 nmol sialic acid (SA) per mg protein (castrated animals injected subcutaneously with 10 mg testosterone/0.1 ml DMSO for four days). This increase was due to the increase in GD3 ganglioside from 0.03 to 0.12 nmol SA/mg protein, and to the decrease of GM3 ganglioside from 0.06 to 0.03 nmol SA/mg protein by testosterone administration. The major ganglioside in the rat kidney was GM3, constituting 63% (control group) and 51% (castrated animals injected daily with 10 mg testosterone) of all gangliosides. Castration itself induced an increase in the rat kidney SAT I and SAT II activities from 712 +/- 130 to 1723 +/- 412 pmol/h x mg protein and from 208 +/- 48 to 751 +/- 176 pmol/h x mg protein, respectively. However, subsequent administration of testosterone, at the highest concentration tested, reversed this effect. In the kidneys of castrated rats, a mixture of beta-estradiol and progesterone decreased SAT II activity from 208 +/- 48 to 87 +/- 33 pmol/h x mg protein.

Animals↗

Effect of anti-ganglioside antibodies on the metastatic spread of intraocular melanomas in a nude mouse model of human uveal melanoma.

In vivo and in vitro studies were performed to determine: (a) if human uveal melanoma cells expressed GD2 and GD3 gangliosides; (b) if anti-GD2 monoclonal antibodies would inhibit the propensity of human uveal melanoma cells to localize in the liver following intravenous injection; and (c) if anti-GD2 monoclonal antibody would reduce the spontaneous metastasis of primary intraocular melanomas in nude mice. The results showed that all three of the human uveal melanoma cell lines tested expressed GD2 and GD3 gangliosides in vitro and in vivo. The human uveal melanoma cell lines preferentially localized in the liver and entered the hepatic parenchyma following spontaneous metastasis from the eyes of nude mice. In vivo administration of anti-GD2 monoclonal antibody produced a sharp reduction in the number of uveal melanoma cells that disseminated to the liver following either intravenous injection or by spontaneous metastasis from primary intraocular melanomas. Collectively, the results demonstrate that uveal melanoma cells display a propensity to localize in the liver after entering the bloodstream; however, this localization can be significantly inhibited by in vivo administration of anti-ganglioside antibodies. The expression of GD2 and GD3 surface gangliosides on uveal melanomas and the capacity of anti-ganglioside antibodies to inhibit metastasis formation in mouse models of ocular and cutaneous melanomas raise the possibility of implementing anti-ganglioside antibodies as potential therapeutic agents for the management of uveal melanoma.

Animals↗

Anti-ganglioside antibodies in new onset type 1 diabetic patients and high risk subjects.

Insulin dependent (type 1) diabetes mellitus appears to be a genetically determined autoimmune disease. Gangliosides have been implicated in type 1 diabetes as antigenic determinants recognized by islet cell antibodies (ICA) and shown to be able to modulate autoimmune phenomena in experimental diabetes. In order to explore in type 1 diabetes the humoral immune reactivity against gangliosides, taking into account their pancreatic localization and molecular characteristics, antibodies to gangliosides GM3, GM2, GM1, GD3, GD1a, GD1b, and GT1b have been investigated in sera from new onset type 1 diabetics and relatives of type 1 diabetic patients with or without insulin (CIAA) and/or islet cell autoantibodies. Using a purposefully designed sensitive ELISA method we found that presence of antibodies directed against the pacreatic disialo-ganglioside GD3 in a significant percentage of newly diagnosed type 1 diabetics (p < 0.001 vs normal controls) but not in CIAA and/or ICA positive relatives of type 1 diabetics. These findings confirm the involvement of gangliosides in autoimmune phenomena related to type 1 diabetes and suggest disialo-ganglioside GD3 as target of a humoral immune response associated with the onset of insulin-dependent diabetes.

Adolescent↗

Patterns of ganglioside expression in B cell neoplasms.

Twenty seven B cell neoplasms were examined by high performance thin layer chromatography (HPTLC) and immune thin layer chromatography (ITLC) to determine ganglioside expression. Patterns of expression in the cells were compared with conventional morphology, genotype, and glycoprotein immunophenotype. Patterns of ganglioside expression were found for each of the tumor types analyzed (5 acute lymphoblastic lymphomas (ALL), 5 Burkitt's Lymphomas (BL), 4 chronic lymphocytic leukemias (CLL), and 3 diffuse poorly differentiated lymphomas (DPDL), 7 diffuse histiocytic lymphomas (DHL), and 3 multiple myelomas (MM). GM3 was the predominant ganglioside found in all B cell neoplasms except multiple myeloma where GM2 was equivalent to GM3. GM1 was detected by ITLC in all B cell tumors, but significant amounts were found by HPTLC only in ALL, CLL, and DHL. Small amounts of GD3 and GD2 were found in several B cell neoplasms. Significant amounts of other gangliosides were not found. The expression of GM2 on the MM cell lines, a cell type derived from outside of the nervous system, is unusual. This high level of expression was also seen in metabolic labeling studies. GM2 was readily detectable in the SKMM1 human multiple myeloma cell line by flow cytometry and served as a target for human complement-mediated cytotoxicity. Although the functions of gangliosides are largely known, the patterns of gangliosides found for this system of human B cell malignancies may serve to provide targets for specific immunotherapy and clues to their functions.

Burkitt Lymphoma↗

Ganglioside inhibition of (125I)-plasmin binding to colorectal carcinoma cells.

The pre-incubation of human colorectal carcinoma cells SW 1116 with 25 to 100 uM purified gangliosides resulted in 35-60% inhibition of specific (125I)-plasmin binding to the cell surface. After 5 to 6 days in culture, tumor cells were pre-incubated at 4 degrees for 1 to 4 h followed by post-incubation with (125I)-plasmin by techniques previously described. At 25 uM the capacity for inhibition of plasmin binding was GT1b greater than GQ1b greater than or equal to GD1a greater than GM1 less than or equal to GgOse 4Cer. Thus a terminal sialyl moiety appears to be necessary (p less than 0.05) although exogenous N-acetyl neuraminic acid was ineffective (p greater than 0.05), indicating a role for the lipid portion of the ganglioside. Other (glyco)lipids such as sphingosine, fucolipid H-1 and sulfatide were without significant effect. The inhibition could not be reversed by the presence of 10 mM Ca+2, EDTA, pre-treatment of the cell with carboxypeptidase or pretreatment of plasmin with neuraminidases. The inhibition was however reversed by post-incubation in control medium without exogenous ganglioside. Cell counts determined prior to, and after ganglioside incubation showed that the effect was not due to cell death or detachment from the culture surface. The dissociation constant for (125I)-plasmin binding was 5.6 x 10(-8) M (700,000 sites/cell), but in the presence of trisialoganglioside (GT1b), Scatchard plots suggested diversification of binding sites with 280,000 sites/cell at Kd 2.6 x 10(-8) M and 820,000 sites/cell at Kd 2.1 x 10(-7) M. Another interpretation of the Scatchard plot in the presence of ganglioside was that the glycolipid imposed negative cooperativity on plasmin binding to the cell surface. These results suggest that certain gangliosides can affect tumor cell invasiveness by altering protease binding to the cell surface.

Binding Sites↗

Effects of ganglioside therapy on experimental CS2 neuropathy.

Both in animals and in man the inhalation of CS2 vapor induces a chronic polyneuropathy with primary lesions in the axons of peripheral nerves. Since it was reported in several studies that the administration of gangliosides improves nerve regeneration and the functional recovery of nerves damaged by section as well as cryodegeneration, a study was undertaken to evaluate the effects of bovine-brain gangliosides administration on the experimental CS2 neuropathy in the rat. One hundred and fifty male rats were intoxicated with CS2 by a discontinuous inhalation exposure to 700 ppm for 12 weeks until a clear neuropathy developed. Thereafter the animals were subdivided at random into five groups and treated in different ways: 10 mg/kg BW gangliosides, 0.5 mg/kg gangliosides, 0.5 mg/kg vitamin B1, and 1 mg/kg vitamin B6, physiological solution, and controls without any treatment. The recovery from neuropathy was controlled for 18 weeks of treatment and assessed periodically by means of clinical, electromyographic, and morphological examination. The results of morphological studies showed more pronounced regeneration activity in the rats treated with the high dose of gangliosides than in all others, while no differences among the groups could be observed as far as clinical and neurophysiological parameters are concerned. The mechanism supporting this ganglioside-induced effect has so far not been ascertained, and further studies on this subject are in progress.

Animals↗

Gangliosides GD1b, GT1b, and GQ1b enhance IL-2 and IFN-gamma production and suppress IL-4 and IL-5 production in phytohemagglutinin-stimulated human T cells.

Gangliosides are sialic acid-containing glycolipids. We studied the in vitro effects of gangliosides on Th1 and Th2 cytokine production in PHA-stimulated human T cells. Gangliosides GD1b, GT1b, and GQ1b (each 100 nM) enhanced PHA-induced IL-2 secretion of peripheral blood T cells approximately 4-fold and enhanced that of IFN-gamma 3- to 4-fold compared with controls. These gangliosides decreased PHA-induced IL-4 secretion by 50-53% and that of IL-5 by 53-63% compared with controls, respectively. The other gangliosides did not alter the secretion of Th1 or Th2 cytokines. RT-PCR showed that GD1b, GT1b, and GQ1b enhanced PHA-induced IL-2 and IFN-gamma transcription and suppressed that of IL-4 and IL-5. Transient transfection assays of Jurkat T cells showed that GD1b, GT1b, and GQ1b enhanced PHA-induced IL-2 and IFN-gamma promoter activities but suppressed those of IL-4 and IL-5. The cAMP analogue dibutyryl cAMP and the cAMP-elevating agents forskolin and 3-isobutyl-1-methylxanthine each reversed GD1b-, GT1b-, and GQ1b-induced stimulation of IL-2 and IFN-gamma production and inhibition of IL-4 and IL-5 production at the levels of proteins, transcription, and promoter activities. GD1b, GT1b, and GQ1b suppressed PHA-induced increase in cAMP level in T cells. These gangliosides suppressed PHA-stimulated adenylate cyclase activity in T cells. These results suggest that GD1b, GT1b, and GQ1b may enhance Th1 cytokine production while suppressing Th2 production by inhibiting adenylate cyclase activity.

Adenylyl Cyclase Inhibitors↗

Exogenous administration of gangliosides inhibits Fc epsilon RI-mediated mast cell degranulation by decreasing the activity of phospholipase C gamma.

Gangliosides released from tumor cells, as well as administered exogenously, suppress the immune responses by largely unknown mechanisms. We show here that a pretreatment of rat basophilic leukemia cells with isolated brain gangliosides inhibited the release of preformed secretory mediators from cells activated via FcepsilonRI but not Thy-1 glycoprotein. Exogenously administered gangliosides also affected the cell-substrate adhesion and the levels of polymeric filamentous actin in Ag-activated cells. Although the production of phosphoinositides was also decreased, enzymatic activity of phosphatidylinositol 3-kinase was not inhibited. Gangliosides had no or only marginal effect on the association of aggregated FcepsilonRI with glycosphingolipid-enriched membranes and on tyrosine phosphorylation of FcepsilonRI and the linker for activation of T cells. Though pretreatment with gangliosides did not inhibit the association of linker for activation of T cells with phospholipase C (PLC)gamma1 and PLCgamma2, tyrosine phosphorylation of these enzymes, as well as their enzymatic activities and association with detergent-insoluble signaling assemblies were reduced. This resulted in a decreased production of inositol 1,4,5-trisphosphate and an inhibition of Ca(2+) mobilization. The combined data support the concept that exogenously administered gangliosides interfere with those properties of glycosphingolipid-enriched membranes that are important for the formation of plasma membrane-associated signaling assemblies containing PLCgamma but not for initial tyrosine phosphorylation of FcepsilonRI subunits.

Animals↗

Complex gangliosides at the neuromuscular junction are membrane receptors for autoantibodies and botulinum neurotoxin but redundant for normal synaptic function.

One specialization of vertebrate presynaptic neuronal membranes is their multifold enrichment in complex gangliosides, suggesting that these sialoglycolipids may play a major functional role in synaptic transmission. We tested this hypothesis directly by studying neuromuscular synapses of mice lacking complex gangliosides attributable to deletion of the gene coding for beta1,4 GalNAc-transferase (GM2/GD2 synthase), which catalyzes an early step in ganglioside synthesis. Our studies show that complex gangliosides are surprisingly redundant for regulated neurotransmitter release under normal physiological conditions. In contrast, we show that they are membrane receptors for both the paralytic botulinum neurotoxin type-A and human neuropathy-associated anti-ganglioside autoantibodies that arise through molecular mimicry with microbial structures. These data prove the critical importance of complex gangliosides in mediating pathophysiological events at the neuromuscular synapse.

Acetylcholine↗

Gangliosides of human kidney.

Five gangliosides isolated from human kidney have been characterized. The two main fractions were shown to be typical extraneural gangliosides in having lactose as their neutral carbohydrate moiety. Their structures were identified as: AcNeu(alpha2-3)Gal(beta1-4)Glc(beta1-1)Cer and AcNeu(alpha2-8)AcNeu(alpha2-3)Gal(beta1-4)Glc(beta1-1)Cer. The two main hexosamine-containing gangliosides are structurally related to human blood group substances of glycosphingolipid nature. The following structures are postulated: AcNeu(alpha2-3)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)Glc(beta1-1)Cer and AcNeu(alpha2-3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)Glc(beta1-1)Cer. The third hexosamine-containing ganglioside belongs to a different series of glycolipids and was shown to have the structure of a major ganglioside of human brain: AcNeu(alpha2-3)Gal(beta1-3)GalNAc(beta1-4)[AcNeu(alpha2-3)]Gal(beta1-4)Glc(beta1-1)Cer. The fatty acid structure of different gangliosides was shown to resemble that of neutral glycolipids of human kidney with the nonhydroxy acids C16:0, C22:0, and C24:0 as major components.

Acetylgalactosamine↗