Sulfatide biosynthesis

It thus seems more likely that the varied sulfatide profiles displayed by the testis of the animals listed in Table III will be explained by differing potentials, among species, of that organ to synthesize the lipid moieties, and by the specificities for both the lipid acceptors and the sugar donors of the glycosyl transferases involved in the second stage of sulfatide biosynthesis (cf.32). 

L.L. Sarlieve, R. Bouchon, C. Koehl and N.M. Neskovic, Cerebroside and sulfatide biosynthesis in the brain of Snell Dwarf mouse effects of thyroxine and growth hormone in the early postnatal period, J. NeurochCTi. 40 1058 (1983). 

The sulfatide biosynthesis has been correlated with the process of myelination (Basu et al., 1968). The formation of the cerebroside-sulfuric acid esters proceeds by the following reaction (Balasubra-manian and Bachhawat, 1965 McKhann and Ho, 1967) ... 

A more detailed publication has appeared recently in which sulfatide biosynthesis is described (Cumar et al., 1968). Sulfotransferase activity for ceramide galactoside was detected in all cerebral subceliular particles examined, including the soluble fraction. The bulk of activity was present in the crude mitochondrial portion, presumably in the synaptosomes. ilicrosomes exhibited the highest specific activity and a deoxycholate extract of these particles was examined more extensively. This prepara tion was employed principally for comparison of the sulfation of lactose and ceramide iactoside. An apparent K for ceramide galactoside varying from 3.3 to 8.5 X 10 M was reported. The product had chrnmatr raphic properties similar to sulfatide. 

A dramatic increase (approx. 50-fold) of the activity of the sulfotransferase involved in the biosynthesis of the SGG also occurred when spermatocytes first began to appear in rat testis (19) the rise in the activity of this enzyme preceded by several days a marked rise in the amount of the SGG. Studies on pre-puber-tal human testis (which is temporarily blocked in spermatogenesis at a stage prior to the appearance of primary spermatocytes) have shown that neither SGG nor GG is present (15,26). Similarly, the testis of the pre-pubertal fowl also lacks sulfogalactosylceramide, the sulfatide found in mature fowl testis (26). All of these find-... 

Fujibayashi, S., and Wenger, D. A., Biosynthesis of the sulfatide/GM activator protein (SAP-1) in control and mutant cultured skin fibroblasts. Biochem. Biophys. Acta 873, 534-562 (1986). 

Fig. 33.34. The synthesis of 3 -phosphoadenosine 5 -phosphosulfate (PAPS), an active sulfate donor. PAPS donates sulfate groups to cerebrosides to form sulfatides and is also involved in glycosaminoglycan biosynthesis (see Chapter 49). Ad = adenosine.

Little is known of the biosynthesis, breakdown, or role of sulfatides. Two observations seem established the biosynthesis of sulfatides coincides with the appearance of myelin and studies with the aid of a radioactive precursor have established a slow but definite turnover of sulfatides in the adult brain. Consequently, the brain constantly synthesizes and degrades sulfatides. Similar anabolic and catabolic processes are likely to occur in other tissues. 

The pathogenesis of ML is unknown. Theories proposed by various authors are difficult to substantiate, particularly since the biosynthesis of sulfatides has not been elucidated (Goldberg 1961 see also chapter by Burton, page 131). The basic lesion(s) may theoretically consist of one or more of the following ... 

In the brain, two distinct pathways of glycosphingolipid biosynthesis have been characterized (Fig. 3.12). The first one leads to myelin galactolipids (GalCer, sulfatide, and GM4) (Fig. 3.13), whereas the second one includes all other glycosphingolipids (both neutral and anionic) derived from glucosylceramide (GlcCer) (Fig. 3.14). 

FIGURE 3.13 Biosynthesis of myelin galactosphingolipids. Ceramide (Cer) is the precursor of GalCer. GalCer can be sulfated (Sulf) or sialylated (ganghoside GM4). GalCer, sulfatide, and GM4 are major component of the human myelin. 

Fig. 3. Pathways of biosynthesis of neutral glycosphingolipids and sulfatides. Numbers in parentheses indicate reference cited. Key to references (1) Cleland and Kennedy, 1960 (2) Hildebrand et al. (1970) (3) Kanfer (1969) (4) Morell and Radin (1970a) (5) Braun et al. (1970) (6) Morell and Radin (1970b) (7) Sribney (1966) (8) Basu (1968) (9) Basu et al. (1968) (10) Nishimura et al. (1966) (11) Fujino and Nakano (1969) (12) Morell and Radin (1969) (13) Balasubramanian and Bachhawat (1965) (14) Hauser (1967) (15) McKhann and Ho (1967) (16) Hildebrand and Hauser (1969) (17) Basu et al. (1970).

The adenosine-3 -phosphate-5 -phosphosulfate (PAPS) generating system could be located in the 105,000 g supernatant of rat brain, whereas the Gal-Cer sulfotransferase remained particle bound. Substrate may be Gal-Cer or lactosyl ceramide. Sulfatides of kidney show a higher metabolic turnover than those in brain. Water-soluble sulfatide, discovered in the 105,000 g supernatant of a brain homogenate, was found to be complexed to certain specific proteins (Hersch-kowitz et al., 1968). It was postulated that this might represent a transport form from the site of biosynthesis to the myelin. 

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