Cerebrosides degradation

A cerebroside was isolated from S. commune and purified by HPLC. Its structure was elucidated by mainly chemical methods of degradation followed by nuclear magnetic resonance and mass spectrometry of the different constituents (78). 

The activator of cerebroside sulfatase (or sulfatide activator ) was purified by Fischer and Jatzkewitz (1975) from human liver and identified as a water-soluble glycoprotein with an isoelectric point at pH 4.3 and a molecular weight of approximately 22,000 Daltons. From kinetic and binding experiments and from the fact that this cofactor stimulated only the degradation of lipid substrates but not of artificial water-soluble ones, these authors concluded that the cofactor serves to solubilize the lipid by binding to it and extracting it from the membrane (or micelle). The resulting activator/lipid complex was assumed to be the true substrate of the enzymic reaction (Fischer and Jatzkewitz, 1977, 1978). 

A new cerebroside has been isolated from the fungus, Fusicoccus amygdaliP Its structure was confirmed by chemical degradation studies and application of n.m.r. spectroscopy and m.s. and was found to be. /V-2-hydroxy-3-rmn -octa-decenoyl-l-0- 3-D-glucopyranosyl-9-methyl-cz>4, x 8-sphingadiene. 

The activity of at least some of the enzymes involved in cerebroside breakdown is increased when the life span of red cells is reduced. Senescent and injured cells are selectively destroyed in the spleen. Part of the degradative process consists of hydrolyzing the membrane s neutral lipids lecithin, phosphatidyl eth-anolamine, sphingomyelin, phospholipids, and the cerebroside globoside. The increased red cell destruction by phenylhydrazine is accompanied by a significant increase in activity of spleen glucocerebrosidase and sphingomyelinase [121]. 

Fig. 7. Degradation of red cell glycolipids and formation of cerebrosides. Pathway A proposed by Philippart et al. (1965) pathway B proposed by Statter and Shapiro (1965). The suspected location of the lesion in Gaucher s disease is at step IV...

In 1958, Jatzkewitz made the important discovery that the metachromatic material in leucodystrophy consists of cerebroside-sulfuric acid esters, proving that ML was indeed a lipid storage disease. The differentiation of leucodystrophies with prelipoid and metachromatic degradation products was now abolished. Recent reports by Austin (1957 a, b), Hagberg et al. (1960—1962), Sourander and SvENNERHOLM (1962), IsLER, Bischoff and Esslen (1963), Hollander and Pilz (1964), Fullerton (1964), and Jatzkewitz (1958—1965) underlined the existence of ML as a distinct cerebral sphingolipidosis. 

In contrast, Jatzkewitz (1960), on the basis of studies in normals and patients with ML, suggested that normally sulfatides are degraded to cerebrosides by removal of the sulfuric acid moiety and that the block in ML is located at this step. 

In 1963, Mehl and Jatzkewitz succeeded in isolating fractions with cerebroside-sulfatase activity from pig kidneys, and Bleszynski and Dzialoszynski (1965) purified soluble arylsulfatases from ox brain. A study by Mehl and Jatzkewitz (1965) on the significance of a lack of arylsulfatase in ML as reported by Austin (1963 a), and Austin et al. (1964 a, b), with 2-hydroxy-5-nitrophenyl-sulfate as substrate, resulted in the finding of two fractions with arylsulfatase activity in normal kidneys. While in ML the smaller of both fractions was present in normal concentration, the second component, and the predominant one in normals, was below the limits (0.005 o. d. units Mehl and Jatzkewitz 1965) of the method in ML. It seems that diminution or lack of this heat-labile fraction, which corresponds to the arylsulfatase A of Austin, is typical for ML, and according to Mehl and Jatzkewitz (1965), supports the assumption of a block in the degradation of ML between sulfatides and cerebrosides (see fig. 3). 

A lipidosis, characterized by the accumulation of sulphuric acid esters of cerebrosides in nervous tissue, due to a deficiency of the degradative enzyme, cerebroside sulphatase. Progressive paralysis and hypotonia are among the clinical findings resulting in death after a few years. 

Three ethylenic amino alcohols, which may derive from the degradation of ceramides or cerebrosides and which are strongly antifungal (Candida albicans), were isolated from another undetermined species of the genus Didemnum harvested on the Great Barrier Reef. Other long-chain amino alcohols seem specific to the family Polyclinidae (see below). 

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