Cerebrosides metabolism

The basic lesion in Gaucher s disease has not yet been elucidated. The storage of cerebrosides, and their identification as glucocerebrosides have stimulated intensive studies on a possible abnormality of cerebroside metabolism. These have... 

Consideration of a primary defect in cerebroside metabolism calls for answers to the following questions 1) is there only a quantitative disturbance, i.e. a balance problem between cerebroside synthesis and breakdown, or 2) is there a qualitative abnormahty of cerebroside metabolism, evidenced by a) the finding of an abnormal cerebroside and/or b) an abnormal relation between various cerebrosides which are defined by their sugar and fatty acid moieties respectively, and 3) is the presumed metabolic error limited to certain cells, i.e. cells which are to become GC, or is it a general feature of all cells with the ability to synthesize and metabolize cerebrosides. 

Imbalances of brain amino acids may hinder the synthesis of brain lipids, leading to a diminution in the rate of myelin formation. Decreases of lipids, proteolipids and cerebrosides (Ch. 3) have been noted in several of these syndromes, e.g. maple syrup urine disease, when intra-myelinic edema is a prominent finding, particularly during the acute phase of metabolic decompensation [9]. Pathological changes in brain myelin are common, especially in infants who die early in life. The fundamental... 

Differences in nutritional effects between PLs and TAGs can be caused by several factors not related to their fatty acid composition, such as the presence of a phosphate group and a nitrogen base (mainly chohne) that may interact in several metabolic pathways (82). Moreover, several glycerophospholipid preparations studied can contain other components such as cholesterol, cerebrosides, sphingomyelins also depending on their source, method of isolation, and purification. These components may also affect the nutritional properties. In this chapter, the metabolic fate of constituent fatty acids of PLs and TAGs will be compared. 

Myelin is approximately 75% lipid and 25% protein. Carbohydrate residues are associated with both the lipid and the protein components of myelin. High proportions of cholesterol, phospholipid, and glycolipid are found in the lipid fractions. Phospholipids include ethanolamine phosphatides, phosphatidylserine, and phosphatidylinositol glycolipids include both neutral (cerebroside, sulfatide, galactosyldiglyceride) and polar (gangliosides, especially GMj and GMJ lipids. A classification and discussion of the metabolism of brain lipids is beyond the scope of this article readers are referred to Lajtha (1969), Davison (1968), Awasthi and Srivastava (1980), and Suzuki (1981). 

Porter, M. T., Fluharty, A. L., and Kihara, H., Correction of abnormal cerebroside sulfate metabolism in cultured metachromatic leukodystrophy fibroblasts. Science 172, 1263-1265 (1971b). 

Glucosylceramide is known to be the precursor of all the major classes of glycosphingolipids in mammalian tissues, while its counterpart, galactosyl-ceramide (GL-lb or cerebroside) gives rise only to a small group of glycolipids. The metabolism of galactosylceramide is discussed later. 

It seems that a large proportion of adult rat, rabbit, or chicken brain cholesterol undergoes very slow metabolism. Since about 70% of brain cholesterol is located in the myelin sheath, it is probable that at least part of this structure is metabolically a relatively stable tissue component. Other studies on brain lipids support this view. Thus distribution of rat brain cerebroside sulfate is similar to that of cholesterol and turnover of sulfatide is also exceedingly slow. Furthermore, Davison and Gregson (1962) found that persisting radioactivity was associated primarily with the myelin fraction prepared from brains of rats previously injected with S -sulfate or methionine. 

V. Ferret-Sena, A. Sena, G. Rebel, A. Pascual, L. Freysz, G. Vincendon and L.L. Sarlieve, Nuclear triiodothyronine receptors and mechanisms of triiodothyronine and insulin action on the synthesis of cerebroside sulfotransferase by cultures of cells dissociated from brain of embryonic mice, m "NATO ASI Series Enzymes of Lipid Metabolism II , L. Freysz, H. Dreyfus, R. Massarelli and S. Gatt, eds.. Plenum Press, New York, pp. 597-613 (1986). 

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. 

Two enzymes have activities related to the metabolism of sulfatides a sulfatase, which is capable of hydrolyzing sulfatides to yield cerebroside and sulfate, and a sulfatide synthetase, which catalyzes the formation of cerebroside and a sulfate donor (phosphoa-denosine phosphosulfate). The exact role of these enzymes in the overall sulfatide metabolism is not clear. A galactosylglucosyl ceramide esterfied with sulfuric acid in position 3 of the galactose has been found in kidney. The dihexose ceramide sulfatide is believed to be synthesized from the neutral ceramide in presence of phosphoadenosine phosphosulfate. The synthetase is a microsomal enzyme. The sulfatase is believed to be a lysosomal enzyme. 

Fredrickson, D.S. Cerebroside lipidosis Gaucher s disease. In The metabolic basis of inherited disease (Stanbury, J.B., Wyngaarden, J.B., and Fredrickson, D.S., eds.), 2nd ed., p. 565-585. New York McGraw-Hill Book Company 1966... 

While the first mention of a sulfolipid in brain tissue was in 1884 (Thudichum), definitive studies on the structure of cerebroside sulfates are still in progress (Yamakawa et al. 1962 Stoffyn and Stoffyn 1963 Taketomi and Yamakawa 1964). Similarly, the metabolism of cerebroside sulfates is largely unknown. Brain... 

Among the unexplained features is the storage of glycolipid by the infantile brain in same cases of GD. Here the possiblity of an additional metabolic error exists. A case (Jervis et al. 1962) where cytoside was the main splenic lipid instead of glucocerebroside (Rosenberg 1962) may represent a variant of GD where the enzymetic defect is localized to the site of cleavage of cytoside to cerebroside (see figure 7). 

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