Cerebrosides, accumulation

Cerebrosides accumulate in the reticuloendothelial cells in Gaucher s disease. The cerebroside content of spleen and liver is increased tenfold however, an increase in the cerebroside content of brain has not been convincingly demonstrated. 

In addition to the cerebrosides, which contain only one carbohydrate residue, there are other glycosphingolipids in mammalian cells that contain more than one sugar component. These oligosaccharide derivatives are called globosides. For example, lactosyl ceramide (1-O-lactosyl-A acylsphingosine) is a constituent of the erythrocyte membrane. Ceramide trihexoside accumulates in the kidneys of patients with Fabry s disease, due to the lack of a lysosomal a-galactosidase A activity. 

Cerebrosides other than sulfatides are decreased ceramide dihexoside sulfate accumulates. 

CGT) and cerebroside sulfotransferase (CST) neuronal lipid storage was provoked. CGT-transgenic ASA(—/—) [CGT/ASA(—/—)] mice showed an accumulation of Cl8 0 fatty acid-containing sulfogalactosylceramide in the brain. Histochemicaly, an increase in sulfolipid storage could be detected in central and peripheral neurons of both CGT/ASA(—/—) and CST/ASA(—/—) mice compared with ASA(—/—) mice. CGT/ASA(—/—) mice developed severe neuromotor coordination deficits and weakness of hindlimbs and forelimbs. 

Several diseases—Gaucher s, Tay-Sachs, Niemann-Pick, and Fabry s diseases, and the leukodystrophies— are characterized by accumulation of lipoid material in cells. These diseases differ in the composition and site of the lipoid accumulation. Whereas gangliosides accumulate in Tay-Sachs disease, sphingosides are found in Niemann-Pick disease, and cerebrosides in... 

Gaucher s disease. Gangliosides accumulate primarely in the cells of the nervous system, but sphingosides and cerebrosides pile up in the reticuloendothelial cells [108, 109]. 

The lipoid compounds that accumulate in the ganglion cells are gangliosides. In infantile amaurotic familial idiocy, the grey matter contains 10-20 times the amount of gangliosides found in normal individuals. In contrast, the levels of cerebrosides and sphingomyelins are normal. (A case has been described in which the levels of both cerebrosides and gangliosides of the brain were increased.)... 

Gaucher s disease is a hereditary disease transmitted by an autosomal recessive or dominant gene and characterized by the accumulation of cerebrosides in reticuloendothelial cells. 

Clinical Pathology. When Gaucher described the disease for the first time, he emphasized three symptoms splenomegaly, hepatomegaly, and skin pigmentation. Later, lipoid material was found in the reticuloendothelial cells, and 1924 it was shown that the compounds that accumulate in those cells are cerebrosides [116-119]. 

Cerebroside Structure and Metabolism. The structure of cerebrosides is particularly important because it has been claimed that those that accumulate in Gaucher s disease are abnormal. The general formula of cerebrosides includes equimolecular amounts of hexose, sphingosine, and fatty acids. 

In addition to the ordinary cerebrosides already described, the brain contains cerebroside sulfates, or sul-fatides—lipid esters composed of a ceramide galactose and sulfate. The exact structure of the sulfatides is not known, but it has been proposed that the carbon 3 of galactose is involved in the formation of an ester bond with sulfuric acid. Sulfatides have been found in a number of tissues (liver, kidney, lung, heart, muscle, spleen), but brain seems to contain the highest concentration of sulfatides. Sulfatides are likely to accumulate in two forms of hereditary lipoidosis met-achromatic leukodystrophy and Fabry s disease. Both these diseases are rare and will be considered only briefly. 

Cerebrosides and sphingomyelin are believed to accumulate in the globoid bodies. In fact, the injection of cerebrosides into rats has led to the appearance in the white matter of cells that resemble globoid cells. The biochemical defect in Krabbe s disease is still unknown, but two clues are available. There are no defects in sphingomyelin breakdown, there is a shift in the ratio of cerebrosides to sulfatides (from 3 to 1 in the normal individuals to 12 to 1 in those with leukodystrophy. These observations have led to the suggestion [127-130] that the lipidosis results from a deficiency of a sulfate-transferring enzyme (see Fig. 3-43). 

Fig. 3-44). Careful examination of all organs might reveal the presence of metachromatic granules in the renal tubules, the gall bladder, and the intrahepatic bile ducts. In metachromatic leukodystrophy, the levels of sulfatides increase more (2 to 4 times) in the white than in the grey matter. The increase in sulfatides is associated with an increase in cerebrosides. The concentration of the other lipids is nearly normal. The proportion of sphingolipids containing long-chain fatty acids (18 or more carbons) is decreased in metachromatic leukodystrophy, and the ceramides found in the accumulating lipids contain mainly short-chain fatty acids. The relationship between the lipid accumulation and the demyelinization and the symptoms of leukodystrophy remains to be elucidated.

KogaJ, Yamauchi T, Shimura M et al (1998) Cerebrosides A and C, sphingolipid elicitors of hypersensitive cell death and phytoalexins accumulation in rice plants. J Biol Chem 273 31985-31991... 

Normal cerebrosides from brain are galactocerebrosides. An accumulation of glucocerebrosides has been found in Morbus Gaucher (Klenk 1940 Rennkamp 1942). 

Other authors have confirmed the radioactive sulfate incorporation data (Green and Robinson, 1960 Bakke and CoRNATZER, 1961 Davison and Gregson, 1962 Kataoka, 1962 and Burton, unpublished data). While Burton (unpublished data) has obtained results consistent with those of Rad in s for the persistence of radioactive sulfate in the cerebroside sulfate fraction. Burton s experiments indicate the same rate of loss of radioactivity due to in the carbohydrate moieties of cerebroside and cerebroside sulfate whereas Radin et al. found a retension of as well as Hauser (1964) and others (Bakke and Cornatzer, 1961, Davison and Gregson, 1962) have observed that the cerebroside cerebroside sulfate ratio in brain tissue appears to remain constant even though these lipids accumulate with age. Thus Hauser (1964) found ratios of 3 in 20 day-old rats and 4 in adult animals. Further experiments need to be carried out to determine... 

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