Brain cerebroside synthesis

It is important to know when in the course of brain development cerebrosides are synthesized because such information might give some clues on the pathogenesis of Gaucher s disease and also some forms of mental deficiency. In rodents, cerebrosides are not actively synthesized during embryonic life or at birth. In mice, the incorporation of labeled hexoses in cerebrosides occurs approximately four days after birth and in rats, seven days after birth. In either case, the synthesis of brain cerebrosides seems to precede that... 

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). 

Similar studies designed to measure the turnover of cerebrosides of brain tissue have been carried out by a number of investigators. Davison et al. (1959) employed serine-3-to label brain cerebrosides and computed the turnover rate to be near 200 days. On the other hand Hajra and Rad in (1964) administered acetate-and measured the rate of loss of radioactivity from the fatty acid moieties of the cerebrosides. In the latter experiments the half-time was near 42 days. When the hexose of the cerebrosides is labeled by means of glucose-1- C or galactose-1- C, the rate of depletion of the isotope indicated a half-time of near 40 days (Burton, et al, 19 ). These data indicate that cerebrosides turn over slowly in brain, at a rate near 40 days, as measured by the hexose and fatty acid moieties. The data derived from the serine experiment undoubtedly indicates that the sphingosine pool in brain is small and that this compound is reused in the synthesis of the sphingolipids. 

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. 

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). 

The biochemical buildup of the brain is far from complete at birth, and the biosynthesis of brain lipids is essential to the proper development of the child. Among the lipids found in brain are gangliosides, cerebrosides, and sphingomyelins. The synthesis of these lipids assumes particular importance when the nerve... 

A recent abstract and verbal report by McKhann, Levy, and Ho (1965) reports the in vitro synthesis of cerebroside sulfate by a microsomal enzyme system from young rat brain (18— 22 days old). Sonic irradiation of the microsomal fractions resulted in the solublization of a sulfokinase system. The complete synthesis required the microsomal fraction of brain, S04 , ATP, cerebrosides, and a non-ionic detergent (Bbij 96). The reaction reported would be consistant with equations 8, 9, and 10. No incorporation of S-sulfate into a cholesterol ester nor an exchange with unlabelled cerebroside sulfate was observed. 

---