Cerebroside sulfate

EC 3.1.6.1) is a lysosomal enzyme that hydrolyzes sulfuric acid ester bonds. The enzyme exists in two forms, arylsulfatases A and B, that differ in substrate specificity and in sensitivity toward inhibitors [142][143]. Human tissues contain more arylsulfatase A than arylsulfatase B. The natural substrates of these enzymes are complex lipids such as cerebroside 3-sulfate, and gly-cosaminoglycans such as chondroitin 4-sulfate and derman sulfate [144], Deficiencies of these enzymes are associated with a number of lysosomal disorders. 

Arylsulfatase [EC 3.1.6.1 ], also known simply as sulfatase, catalyzes the hydrolysis of a phenol sulfate, thereby producing a phenol and sulfate. This enzyme classification represents a collection of enzymes with rather similar specificities. (1) Steryl-sulfatase [EC3.1.6.2],also referred to as arylsulfatase C and steroid sulfatase, catalyzes the hydrolysis of 3-j8-hydroxyandrost-5-en-17-one 3-sulfate to 3-j8-hydroxyandrost-5-en-17-one and sulfate. The enzyme utilizes other steryl sulfates as substrates. (2) Cere-broside-sulfatase [EC 3.1.6.8], or arylsulfatase A, catalyzes the hydrolysis of a cerebroside 3-sulfate to yield a cerebroside and sulfate. The enzyme will also hydrolyze the galactose 3-sulfate bond present in a number of lipids. In addition, the enzyme will also hydrolyze ascorbate 2-sulfate and other phenol sulfates. 

This enzyme [EC 3.1.6.8], also known as arylsulfatase A, catalyzes the hydrolysis of a cerebroside 3-sulfate to produce a cerebroside and sulfate. The enzyme will also catalyze analogous reactions on the galactose 3-sulfate residues in a number of lipids as well as on ascorbate 2-sulfate and many phenol sulfates. 

The mechanism of action of this activator has not been established, but it is known (Fischer and Jatzkewitz, 1978 Mitsuyama et al., 1985) that the activator forms an equimolar complex with cerebroside 3-sulfate prior to hydrolysis by arylsulfohydrolase A. Similar heat-stable activator proteins are also known for other acid hydrolases (Li and Li, 1983 Inui and Wenger, 1983 Wenger and Inui, 1984 Conzelmann et al., 1982 Christomanou and Kleinschmidt, 1985 Burg et al., 1985). It is becoming increasingly evident that many lysosomal hydrolases have specific activators, although some of these activators may be common to more than one enzyme (Li and Li, 1983, 1984 Li et al., 1985). The desulfation of cerebroside 3-sulfate also occurs in the absence of activator protein. In these experiments, Tween-20 or sodium... 

Multiple sulfohydrolase deficiency Cerebroside 3-sulfate, steroid sulfate, and heparan sulfate Arylsulphohydrolases A, B, C, iduronate sulfate sulfohydrolase, )V-acetyl galactosamine 6-sulfohydrolase Brain, bone... 

Several cases of a new form of metachromatic leukodystrophy have been reported (Hahn et al., 1981, 1982 Inui et al., 1983). These cases have clinical symptoms resembling juvenile metachromatic leukodystrophy, but have only about half of the normal arylsulfohydrolase A activity in leukocytes and fibroblasts. The kinetic properties of the arylsulfohydrolase A from fibroblasts are normal. However, the cerebroside 3-sulfate loading test (Porter et al., 1971a) with growing fibroblasts shows an abnormal response, indicating a disturbance in arylsulfatase A activity. Supplementation with the activator (Stevens et al., 1981) of arylsulfatase A results in a normal cerebroside 3-sulfate loading test. This indicates that the new form of metachromatic leukodystrophy is not caused by the deficiency of arylsulfohydrolase A, but rather is caused by a deficiency of the activator protein (Shapiro et al., 1979). Fujibayashi and Wenger (1986) have studied the biosynthesis of sulfa-tide/GMj activator protein in control and mutant cultured skin fibroblasts. Their results indicate that patients with variant form of metachromatic leu-... 

Lott et al. (1976), Dubois et al. (1977), and Butterworth et al. (1978) reported low arylsulfohydrolase A activities in leukocytes and skin fibroblasts from healthy members of a family having a metachromatic leukodystrophy patient. Kihara (1982) called this condition pseudoarylsulfohydrolase A deficiency. During a cerebroside 3-sulfate loading test fibroblasts from this... 

Farooqui, A. A., and Bachhawat, B. K., Enzymatic desulfation of cerebroside 3-sulfate by chicken brain arylsulfatase. /. Neurochem. 20, 889-891 (1973). 

Mehl, E., and Jatzkewitz, H., Cerebroside 3-sulfate as a physiological substrate of arylsulfatase A. Biochim. Biophys. Acta 151, 619-627 (1968). 

Although cerebroside sulfate has been reported to interact strongly with opiates C14-16), enkephalin has so far shown no significant binding in the present type of experiment to an egg lecithin C27 mg) - sulfatide (25 mg) mixture at pH 6.3 and 7.1. Further studies are currently underway with this system. 

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... 

Figure 3. Time course of incorporation of ssSOi>" into cerebroside sulfate (cer-SOk) and sulfogalactosyl glycerol lipid (SGG-lipid) in dissociated brain cells from 15-day mouse embryos grown 19 days in culture...

MDG (monogalactosyl diacyl- and monoacylmonoalkylglycerol),Cer-SO (cerebroside sulfate), and MGD-SO4 (monogalactosyl diacyl- and monoacylmonalkylglycerol sulfate). 

Arylsulfatase cleaves sulfate esters. Cerebroside sulfate is its natural substrate. The enzyme is also active toward p-nitrocatechol sulfate, which is the basis for this assay. 

Boggs JM, Wang H. Effect of liposomes containing cerebroside and cerebroside sulfate on cytoskeleton of cultured ohgodendro-cytes. J. Neurosci. Res. 2001 66 242-253. 

Stewart RJ, Boggs JM. A carbohydrate-carbohydrate interaction between galactosylceramide-containing liposomes and cerebroside sulfate-containing liposomes Dependence on the glycolipid ce-ramide composition. Biochemistry 1993 32 10666-10674. 

Boggs JM, Menikh A, Rangaraj G. Trans interactions between galactosylceramide and cerebroside sulfate across apposed bilayers. Biophys. J. 2000 78 874-885. 

Menikh A, Nyholm P-G, Boggs JM. Characterization of the inter-achon of Ca with hydroxy and non-hydroxy fatty acid species of cerebroside sulfate by fourier transform infrared spectroscopy and molecular modeling. Biochemistry 1997 36 3438-3447. 

With bilayer lipid membranes it is not possible to achieve a fully asymmetric arrangement of head groups or chains. There is no apparent reason why all the molecules of two independent layers should only concentrate in one layer. Nevertheless, a little asymmetric distribution is found in vesicles made of lipid mixtures. Cerebroside sulfate, an anionic monoglycosyl ceramide was, for example, added exclusively to the outer surface of a performed DPPC vesicle (see Scheme 2.2) which was quantitized by the metachromatic effect of acridine orange. 

Opiate narcotics are thought to act at specific receptors in the brain since they exhibit stereospecific binding (1) and have been shown by fluorescence techniques to be localized at discrete regions in the central nervous system (2). While much effort has been made to isolate and characterize the opiate receptor C3), relatively little detailed information exists about the nature of the opiate binding site. Some investigators describe the receptor as a membrane bound protein or proteo-lipid (4) while others have used nerve cell components such as cerebroside sulfate or phosphatidyl inositol as models for the opiate receptor (5). 

There is considerable evidence to support the supposition that cerebroside sulfate might participate in opiate action. The data have been derived not only from in vitro experiments but in vivo ones as well and these papers have been cited and... 

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). 

Metachromatic leukodystrophy Arylsulfatase A or saposin B Cerebroside sulfate, 3-0-suIfogalactosyl-containing glycolipids ... 

Metachromatic arylsulfatase A Leucody-strophy Cerebroside sulfate ARSA 1 40000 LCMS2 screening of urinary sulfatides... 

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. 

J. S. O Brien and G. Rouser, The Fatty Acid Composition of Brain Sphingolipids Sphingomyelin, Ceramide, Cerebroside, and Cerebroside Sulfate, J. Lipid Res. 5, 339-342 (1964). 

Morphine is known to interact sterospecifically with lipids such as cerebroside sulfate and phosphatidyl serine (Abood et al. 1977). 

Morphine has been shown to Interact stereospecifically with such lipids as cerebroside sulfate and phosphatidyl serine (Abood et al. 1977). By analogy, the enkephalins might also show an Interaction with lipid systems, since they are competitive with morphine in vivo. Table 3 shows the results of preliminary studies using lecithins and phosphatidyl serine. 

In addition to the ordinary cerebrosides already described, the brain contains cerebroside sulfates, or sul-fatides—lipid esters composed of a ceramide galactose and sulfate. The exact structure of the sulfatides is not known, but it has been proposed that the carbon 3 of galactose is involved in the formation of an ester bond with sulfuric acid. Sulfatides have been found in a number of tissues (liver, kidney, lung, heart, muscle, spleen), but brain seems to contain the highest concentration of sulfatides. Sulfatides are likely to accumulate in two forms of hereditary lipoidosis met-achromatic leukodystrophy and Fabry s disease. Both these diseases are rare and will be considered only briefly. 

We have recently studied the interactions of adrenocorticotropin, dynorphin, and enkephalin peptides (Table 1) with membranes prepared from phosphatidyl choline, phosphatidylserine, phosphatidic acid, and cerebroside sulfate lipids either singly or in combination, using essentially three methods ... 

It is of interest to point out that this is the order of magnitude for the difference in interaction with liposomes, containing cerebroside sulfate, of all-L and all-D leu-enkephalins (2.5-3.0), as reported by R. Schwyzer and coworkers [27]. 

O Brien, J. S., and G. Rouser The fatty acid composition of brain sphingolipids sphingomyelin, ceramide, cerebroside and cerebroside sulfate. J. Lipid Res. 6, 339 (1964). 

Cerebroside sulfate, a sulfuric acid ester of cerebroside 3 -sulfogalactosyl cera-mide (Yamakawa et al. 1962, Stoffvn and Stoffyn 1963, Taketomi and Yama-KAWA 1964). 

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