Cerebroside synthesis

Estimates of the rate of myelin synthesis can be obtained in vitro from the measurement of cerebroside synthesis, which increases fourfold from day 10 to day 20 in the rat and then slowly decreases along with the overall rate of myelin synthesis. In vivo studies employing radiolabeled precursors of specific myelin components, such as sulfate into sulfatide, yield results similar to those obtained in vitro. In situ studies with tissue slices confirm in vitro and in vivo experiments. These studies also indicate that the appearance of... 

Psychosine was extracted from brain. The biphenylcarbonyl derivatives were separated by high performance liquid chromatography into two different peaks that were eluted with the same retention ti.me as the psychosine standards, using dichloromethane methanol NH3 85 8.5 1.5 by vol. as solvent. We assume tentatively that free psychosine is present in brain. According to these results we can propose a possible pathway of cerebroside synthesis by acylation of brain psychosine. 

Cerebrosides synthesis can occur potentially by two routes 1) the acylation of psychosine to yield cerebroside, and 2) the galactosylation of ceramide. The acylation of psychosine can occur in vitro as demonstrated by Brady (1962) and suggested by the work of Cleland and Kennedy (1960). Brady prepared microsomes from the brains of young rats (14 day old sedimented at 3x10 g-min.). When these microsomal preparations were incubated in phosphate buffer (pH 7.8) with stearyl-l-i C-SCoA, Tween-20, magnesium chloride and ATP, incorporation into cerebrosides of the radioactivity in the stearic acid occurred in the presence of psychosine but not in the presence of sphingosine (unless UDP-glucose was present also). 

Elevation of cerebrosides predominates (Klenk 1940), other glycolipids, which occur in trace amounts in normal tissues and which are probably intermediates of cerebroside synthesis, have recently received increasing attention (Klenk and Rennkamp 1942, Parke 1954, Rapport et al. 1960, Makita and Yamakawa 1962, Spatter and Shapiro 1963, Svennerholm and Svennerholm 1963). The increase in cerebroside content is more marked in the spleen than in the liver. Data from two cases examined by Thannhauser and Reinstein are as follows Spleen... 

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... 

Cerebrosides are major constituents of the membrane of brain cells. They are the simplest glycosphingolipids, serving as model substances for more complex lipids of this kind. Furthermore, they are credited with important properties as receptors for hormones and toxins.29 Schemes 4 13 and 4 14 provide a method for preparing sphingosine and its analogs that can be used for the synthesis of cerebroside compounds. 

The diseases considered here affect only a small fraction of the problems in the catabolism of body constituents. On the other hand, fewer cases are on record of deficiencies in biosynthetic pathways. These are more often absolutely lethal and lead to early spontaneous abortion. However, blockages in the biosynthesis of cerebrosides are known in the special strains of mice known as Jimpy, Quaking, and msd (myelin synthesis deficient).377 378 The transferases (points 11 and 12 of Fig. 20-11) are not absent but are of low activity. The mice have distinct neurological defects and poor myelination of nerves in the brain. 

A partial synthesis of cerebroside sulfate [ sulfatide, the glycoside of ceramide with galactose 3-sulfate, (90)] was achieved [90] by acylating the sphingosine galactosyl 3-sulfate (89) (obtained by basic hydrolysis of natural sulfatide) with palmitoyl chloride or D-2-acetoxypalmitoyl chloride (and subsequent basic hydrolysis of the... 

Cerebrosides are glycosides of ceramides. Accordingly, ceramides must be prepared prior to the synthesis of cerebrosides by glycosidation. Our synthetic plan for 128 is shown in Figure 5.4. Sch II (128) can be... 

After completion of the synthesis of Sch II (128) in 1985, we continued our studies on the cerebro-sides inducing the fruiting-body formation in Schizophyllum commune, and the cerebrosides shown in... 

Figure 5.9 Synthesis of Whe II, a cerebroside isolated from wheat grain with fruiting-body inducing activity against Schizophyllum commune...

The total synthesis of this and similar compounds, carried out by Shapiro and Flowers,68,90 is discussed in the Section on cerebrosides (see p. 401). 

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