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Characteristic constituents of glycolipids from frog brain and sciatic nerve.

Cerebroside, sulfatide, monoglycosyl glyceride, and ester cerebroside were isolated from frog brain and sciatic nerve, and their distribution and chemical constituents were determined. The long-chain base compositions of cerebroside, sulfatide, and ester cerebroside were unique in the presence of branched-base components (5-15% of the total bases) and in the abundance of saturated dihydroxy base components (15-45% of the total). The amount of branched long-chain bases was greater in sciatic nerve than in brain. The hexose composition of the glycolipids consisted entirely of galactose except for brain cerebroside, in which a small amount of glucose was detected. Monogalactosyl glyceride consisted of the diacyl and alkylacyl forms, in a molar ratio of 81:19 for brain and 62:38 for sciatic nerve. The fatty acid composition of glycosphingolipids was characterized by the predominance of hydroxy and nonhydroxy 24:1 acids, and the concentration of 24:0 was extremely low. The proportion of unsaturated fatty acids accounted for 80% of the total. Major fatty acids of monogalactosyl glyceride were palmitic, oleic, stearic, and palmitoleic acids; the highest concentration was that of palmitic acid. Ester cerebroside was separated into three subfractions mainly on the basis of the proportion of hydroxy and nonhydroxy components in the amide-linked fatty acids.

Animals↗

Potentiation of opiate action in neuroblastoma N18TG2 cells by lipid incorporation.

The effect of cerebroside sulfate, phosphatidylserine, and other phospholipids on opiate receptor function in neuroblastoma N18TG2 cells was studied by incorporation of lipids into the membrane bilayer of viable cells. A concentration- and time-dependent incorporation of sulfatide by N18TG2 cells was observed. The incorporated lipid was not metabolized during the incubation period of up to 48 hr at 37 degrees. Optimal conditions for lipid incorporation were determined to be 4 days after the cell seeding and in 1% fetal calf serum. The incorporated lipid was established to be associated with the plasma membrane fraction of the crude cell homogenate. Furthermore, increases in Vmax but not Km values of the adenylate cyclase for Mg2+, ATP, and prostaglandin E1 were observed in neuroblastoma N18TG2 cells exposed to cerebroside sulfate for 4--6 hr. The incorporation of cerebroside sulfate or phosphatidylserine by N18TG2 cells did not increase the number of opiate binding sites in this cell line as determined by [3H]naloxone, [3H]etorphine, or 3H-labeled D-Ala2-Met5-enkephalinamide binding. Although there was an increase in the affinity of [3H]naloxone binding, linear correlation between the amount of cerebroside sulfate incorporated and the quantity of binding increase was not observed. However, augmentation of both the potencies and the efficacies (maximal inhibitory level) of morphine and enkephalin to regulate adenylate cyclase activity was observed after sulfatide incorporation. At the maximal concentration of cerebroside sulfate used (67 microM) the opiate receptor activity in N18TG2 cells approached that of NG108-15 cells. Identical treatment of N18TG2 cells with cerebroside or psychosine sulfate did not produce any potentiation of the opiate inhibition of adenylate cyclase. Of all of the phospholipids tested--phosphatidylserine, phosphatidylinositol, and phosphatidylcholine--only phosphatidylcholine produced a potentiation of the opiate effect. Both synthetic dipalmitoyl phosphatidylcholine or brain phosphatidylcholine could elicit the potentiation.

Adenylyl Cyclases↗

Biochemical studies of metachromatic leukodystrophy in three siblings.

Biochemical analyses were performed on cerebral biopsies from three siblings with metachromatic leukodystrophy, and from autopsy tissue obtained 6 months later. The lipids of all gray matter samples were relatively normal, with the exception of an elevated sulfatide: cerebroside ratio. The white matter samples were grossly abnormal and showed a progression in severity of biochemical abnormalities with duration of the disease. Sulfatides were 4-8-fold higher than normal, and the ratio of cerebrosides to sulfatides ranged from 0.13 to 0.26, compared to the normal value of about 4.0. Myelin was isolated in very low yield, but had normal morphology. As others have reported, it had the same chemical defect as whole white matter; sulfatides were 7-8 times higher than normal and cerebrosides were reduced by more than half. The fatty acid compositions of the myelin sphingolipids were found to be of much longer average chain length than those in affected white matter. In myelin, the unsubstituted fatty acids of cerebrosides and sphingomyelin had a higher percentage of short chains than found in normal myelin, but were less abnormal than those in whole white matter, whereas the unsubstituted and alpha-hydroxy acids of sulfatides and the alpha-hydroxy acids of cerebrosides were not deficient in long chains. These data indicate that there are at least two compartments of sphingolipids in MLD white matter, each having different average chain lengths.

Brain Chemistry↗

Structural alterations of peripheral nerve monogalactosylceramides during development and Wallerian degeneration.

The structural alterations of monogalactosylceramides in peripheral nerve were investigated during development, nerve fiber degeneration and regeneration. During early development, hydroxy cerebrosides and sulfatides were the main constituents of the monogalactosylceramides of immature rat sciatic endoneurium. The ratio of hydroxy to nonhydroxy cerebrosides decreased rapidly as myelination proceeded but remained fairly constant throughout adulthood. More than 50% of the adult content of endoneurial monogalactosylceramides was achieved before 21 days of age. The long-chain nonhydroxy fatty acids (above C21) had increased from under 20% to over 80% by day 20, while 24h:0 (h, hydroxy) had already reached approximately 50% of hydroxy cerebrosides by day 12. These results suggest that the biosynthesis of endoneurial monogalactosylceramides and fatty acid elongation take place preferentially at the time when peripheral nerve is undergoing active myelination. During Wallerian degeneration, the maximum decrease of monogalactosylceramides was associated temporally with axonal degeneration and demyelination and particularly with myelin conversion to sudanophilic lipids. By the time that nerve fiber regeneration was well established, both the cerebroside and sulfatide contents had returned to near control values. Cerebrosides and long-chain fatty acids (above C21) appear to be the most sensitive to fiber degeneration while fatty acid elongation is selectively increased during nerve regeneration.

Animals↗

Galactolipid fatty acid composition in adrenoleukodystrophy.

The non-hydroxy and hydroxy fatty acids of the major brain galactosphingolipids, cerebroside and sulphatide, have been isolated from white matter, gray matter and myelin of 2 children with adrenoleukodystrophy and from a corresponding control. In addition, cerebroside fatty acids were recovered from a myelin-related fraction on 1 patient. In comparison to control observations, myelin and the myelin-related fraction cerebroside demonstrate a loss of C24:1 and C24h:o fatty acids from normal and hydroxy fatty acid fractions, respectively. White and gray matter galactolipids isolated from 1 patient indicated a signficant increase in short chain (C16, C18 and C18:1) non-hydroxy fatty acids. In the isolated diseased myelin, the ratio of cerebroside hydroxy to non-hydroxy fatty acids was elevated about 1.5 times above the value for normal myelin, whereas the ratio derived for the myelin-related fraction was about two-thirds the values for the control myelin cerebroside.

Adrenal Insufficiency↗

Distinct differences in lipid composition between epidermis and dermis from footpad and dorsal skin of guinea pigs.

All lipids, including neutral lipids, phospholipids and glycolipids, in the dermis and epidermis from footpad and dorsal skin of guinea pigs were quantitatively determined, and distinct and characteristic differences in lipid composition were observed in both regions. Ceramides, cerebrosides and cholesterol sulfate were abundant in the epidermis, the amounts being 8.8-12.0, 2.8-4.0 and 6.0-6.5 times higher than those in the dermis, respectively, whereas sulfatide was predominantly found in the dermis. Four and six bands of ceramides, and three and four bands of cerebrosides were detected for the lipids from both the epidermis and dermis on TLC, respectively, two of the ceramides and one of the cerebrosides being found to be esterified. Cerebrosides in the epidermis were predominantly glucocerebrosides, whereas those in the dermis comprised a mixture of gluco- and galactocerebrosides. In addition, an esterified cerebroside, glucosyl N-(O-linoleoyl-omega-hydroxylignoceroyl) sphingosine, was present in the epidermis as a tissue-characteristic compound and this finding seems to be common for several animal species. The marked differences in lipid components between the epidermis and dermis should be quite useful for discriminating these functionally as well as histologically different regions on a biochemical basis.

Animals↗

Biochemical and physicochemical determinations in a premyelin fraction obtained by zonal centrifugation in normal mouse and in dysmyelinating mutants (quaking, shiverer, and myelin-deficient).

Myelin and premyelin material denser than myelin were obtained from quaking (Qk), shiverer (Shi), and myelin-deficient (mld) mutant and control mice, using zonal centrifugation on zonal rotor. On these fractions, we performed biochemical analysis (lipids and fatty acid), and, in parallel, we determined the physical structure of membranes by the spin-label method. The hyperfine splitting constant (2 Tll) was used to determine the order of membranes and their rigidity, and frequency of rotation (Vc) was used to measure fluidity. In control mice, the premyelin material contained a lesser amount of sphingolipids than pure myelin, but the relative proportions between hydroxy- and nonhydroxy-cerebroside and sulfatides were similar in the premyelin material and in pure myelin. The premyelin material contained half the alkanes found in the pure myelin and much less very-long-chain fatty acids. The (2 Tll) was lower in the premyelin material, but the (Vc) was similar in myelin and premyelin material. In mutants, the amount of material recovered in the premyelin fraction was reduced in qk, and increased in both shi and mld. The relative amount of sphingolipids were normal in mld, but not in shi mutants, especially in cerebrosides formed with alpha-hydroxylated fatty acids and sulfatides formed with unsubstituted fatty acids. The absolute amounts of sphingolipids were nearly normal in both shi and mld. In the premyelin fraction from qk mutants, both relative and absolute amounts of sphingolipids were drastically altered. In percentage, cerebrosides and sulfatides formed with nonhydroxyfatty acids were dramatically reduced, and, conversely, cerebrosides and sulfatides formed with hydroxyfatty acids were increased. In terms of absolute amount, only cerebrosides and sulfatides formed with nonhydroxyfatty acids were dramatically reduced. In the premyelin fraction, polyunsaturated fatty acids were increased in shi and mld, but decreased in qk. In this mutant, lignoceric (24:0) and nervonic (24:1) acids were drastically reduced. The amount of alkanes in the premylin material from qk and mld was reduced by 50%. The shi fraction was nearly free of alkanes. The maximal apparent coupling constant (hyperfine splitting constant, 2 Tll) was not affected in the mld and qk mutant, but was reduced in the shi mutant premyelin fraction. The Vc was dramatically increased in the qk, slightly decreased in the shi, and close to control in the mld. This work provides additional data on premyelin material prepared in various neurological mutants using continuous gradients in zonal rotor.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkanes↗

A Contrast of the Plasma Membrane Lipid Composition of Oat and Rye Leaves in Relation to Freezing Tolerance.

The lipid composition of the plasma membrane isolated from leaves of spring oat (Avena sativa L. cv Ogle) was vastly different from that of winter rye (Secale cereale L. cv Puma). The plasma membrane of spring oat contained large proportions of phospholipids (28.8 mol% of the total lipids), cerebrosides (27.2 mol%), and acylated sterylglucosides (27.3 mol%) with lesser proportions of free sterols (8.4 mol%) and sterylglucosides (5.6 mol%). In contrast, the plasma membrane of winter rye contained a greater proportion of phospholipids (36.6 mol%), and there was a lower proportion of cerebrosides (16.4 mol%); free sterols (38.1 mol%) were the predominant sterols, with lesser proportions of sterylglucosides (5.6 mol%) and acylated sterylglucosides (2.9 mol%). Although the relative proportions of individual phospholipids, primarily phosphatidylcholine and phosphatidylethanolamine, and the molecular species of these two phospholipids were similar in oat and rye, the relative proportions of di-unsaturated species of these two phospholipids were substantially lower in oat than in rye. The relative proportions of sterol species in oat were different from those in rye; the molecular species of cerebrosides were similar in oat and rye, with only slight differences in the proportions of the individual species. After 4 weeks of cold acclimation, the proportion of phospholipids increased significantly in both oat (from 28.8 to 36.8 mol%) and rye (from 36.6 to 43.3 mol%) as a result of increases in the proportions of phosphatidylcholine and phosphatidylethanolamine. For both oat and rye, the relative proportions of di-unsaturated species increased after cold acclimation, but the increase was greater in rye than in oat. In both oat and rye, this increase occurred largely during the first week of cold acclimation. During the 4 weeks of cold acclimation, there was a progressive decrease in the proportion of cerebrosides in the plasma membrane of rye (from 16.4 to 10.5 mol%), but there was only a small decrease in oat (from 27.2 to 24.2 mol%). In both oat and rye, there were only small changes in the proportions of free sterols and sterol derivatives during cold acclimation. Consequently, the proportions of both acylated sterylglucosides and cerebrosides remained substantially higher in oat than in rye after cold acclimation. The relationship between these differences in the plasma membrane lipid composition of oat and rye and their freezing tolerance is presented.

Journal Article↗

A survey of neurological mutant mice. II. Lipid composition of myelinated tissue in possible myelin mutants.

The lipids of white matter and peripheral nerve from neurological mutant mice with possible myelin abnormalities were analyzed by thin-layer chromatography and quantitated by densitometry. Eight mutants had major abnormalities in the central nervous system (CNS) and/or peripheral nervous system (PNS) tissues examined (optic nerve, and trigeminal and sciatic nerves). In the optic nerve of axJ/axJ, there were increases of 20-30% in the levels of the major phospholipids; peripheral nerve was normal. In bc3J/bc3J CNS, the major phospholipids and cholesterol were increased by 25-40%; the PNS was normal. In myd/myd CNS, there were increases of about 20% in the levels of both forms of cerebrosides and in the major phospholipids; in the PNS the lipids were normal. ot/ot CNS had 20-40% reductions of all the glycolipids and minor alterations in some of the phospholipids and cholesterol; the PNS had 20% losses of both forms of cerebrosides. In the PNS of ji/ji, there were decreases of 10-40% among the glycolipids and of 15-25% in three of the major phospholipids; the CNS was virtually normal. In the PNS of dtJ/dtJ, vb/vb and wr/wr, almost all lipids were significantly decreased. The CNS of dtJ/dtJ and vb/vb were normal; wr/wr had minor reductions of certain glycolipids and phospholipids. Six mutants had relatively minor lipid abnormalities in their myelinated tissues. In cr/cr PNS, there were elevated levels of the cerebrosides and major phospholipids; the CNS was virtually normal. In db/db CNS and PNS, there were reduced levels of the nonhydroxy forms of cerebroside and sulfatide. The major change in htr/htr was the elevation of all the glycolipids in the CNS. In the CNS of Lc/+, nonhydroxy cerebroside was reduced. In shm/shm PNS, nonhydroxy sulfatide was elevated and there were small decreases in some of the phospholipids. wl/wl CNS showed decreases among most of the glycolipids. Mutants homozygous for du, mto, spa and tg had virtually normal lipid levels in both the optic and peripheral nerves. Cholesterol ester, lysophospholipids and other unusual lipid species were not detected in any of the mutants. The plasmalogen forms of ethanolamine and choline phosphatides were at normal levels in all mutants that otherwise had significant alterations among their lipids. Although many alterations in lipid composition were found in these mutants, the changes were moderate compared to the classical myelin mutants and indicate that none of the mutants are severely myelin-deficient.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Membrane lipid profile of an edible basidiomycete Lentinula edodes during growth and cell differentiation.

The basidiomycetous mushroom Lentinula edodes (Shiitake) exhibits a unique process of cell differentiation termed "fruiting-body formation". To clarify the relationship between membrane lipids and fruiting-body formation in this fungus, we investigated variations in levels of phospholipids, cerebrosides, fatty acyl residues in the major phospholipids, and fatty acyl and sphingoid base residues in cerebrosides during vegetative growth and fruiting-body formation. PC, PE, and PS were the primary phospholipids in the cells of L. edodes. After a shift in growth temperature of L. edodes mycelia has been shifted from 25 to 18 degrees C, the proportion of unsaturated FA (UFA), such as linoleic acid (18:2) and oleic acid (18:1), increased. In contrast, during fruiting-body formation induced by the temperature downshift to 18 degrees C, 18:2 of PC in the primordia and fruiting bodies decreased, and the UFA of PE and 18:1 of PC increased compared with the proportions in mycelia growing at 18 degrees C. These results showed that the proportions of fatty acyl residues in PC and PE differed during fruiting-body formation in L. edodes. Moreover, the amount of cerebrosides in primordia increased compared with those in mycelia and fruiting bodies and, in these differentiating tissues, the proportion of 2-hydroxypentadecanoic acid increased whereas that of 2-hydroxyoctadecanoic acid decreased compared with that in the mycelia. However, the proportion of sphingoid base residues in cerebrosides did not change during fruiting-body formation in L. edodes.

Basidiomycota↗

Lactase-phlorizin hydrolase complex from monkey small intestine. Purification, properties and evidence for two catalytic sites.

Lactase-phlorizin hydrolase (EC 3.2.1.-) has been purified from the monkey small intestine by gel filtration and ion-exchange chromatographic procedures and the properties of the purified enzyme complex have been studied. Lactose was the most active substrate. Cellobiose and other synthetic hetero-beta-glycosides were hydrolysed at a very much reduced rate. The rate of hydrolysis of phlorizin was about 2.5% that of lactose. Lactase and phlorizin hydrolase activities were indistinguishable by heat inactivation experiments. The purified enzyme complex also hydrolysed cerebrosides. Lactose hydrolysis was competitively inhibited by phlorizin as well as by the brain cerebroside. However, there was no mutual inhibition between phlorizin and the brain cerebroside. It is suggested that the native enzyme complex might have two catalytic sites, a phlorizin site and a cerebroside site but both hydrolysing lactose.

Animals↗

Alterations in metabolism and gene expression in brain regions during cuprizone-induced demyelination and remyelination.

Exposure of mice to the copper chelator, cuprizone, results in CNS demyelination. There is remyelination after removal of the metabolic insult. We present brain regional studies identifying corpus callosum as particularly severely affected; 65% of cerebroside is lost after 6 weeks of exposure. We examined recovery of cerebroside and ability to synthesize cerebroside and cholesterol following removal of the toxicant. The temporal pattern for concentration of myelin basic protein resembled that of cerebroside. We applied Affymetrix GeneChip technology to corpus callosum to identify temporal changes in levels of mRNAs during demyelination and remyelination. Genes coding for myelin structural components were greatly down-regulated during demyelination and up-regulated during remyelination. Genes related to microglia/macrophages appeared in a time-course (peaking at 6 weeks) correlating with phagocytosis of myelin and repair of lesions. mRNAs coding for many cytokines had peak expression at 4 weeks, compatible with intercellular signaling roles. Of interest were other genes with temporal patterns correlating with one of the three above patterns, but of function not obviously related to demyelination/remyelination. The ability to correlate gene expression with known pathophysiological events should help in elucidating further function of such genes as related to demyelination/remyelination.

Animals↗

Hematopoietic cell transplantation in murine globoid cell leukodystrophy (the twitcher mouse): effects on levels of galactosylceramidase, psychosine, and galactocerebrosides.

Hematopoietic cell transplantation (HCT) prolongs survival in the twitcher mouse, an authentic animal model of human globoid cell leukodystrophy (Krabbe disease; galactosylceramidase deficiency), but the effects of HCT on levels of galactosylceramidase, psychosine, and cerebrosides in the tissues of twitcher mice have not been previously studied. Galactosylceramidase was less than 8% of control activity in tissues of untreated twitcher mice but reached normal values in brain and spleen and 20-30% of control in kidney of 100-day-old twitchers that received HCT at age 10 days. Using a recently developed method for the simultaneous determination of psychosine and cerebrosides, we measured the tissue levels of these lipids in the above animals. The levels of psychosine in brain, sciatic nerve, and kidney of untreated twitcher mice were 44, 200, and 12 times control values, respectively, in 30-day-old animals and 69, 500, and 14 times control levels in 40-day-old mice. On the other hand, levels of cerebroside were approximately 35% of control values in sciatic nerve, remained about the same in the brain, and were elevated 10-fold in the kidney of twitcher mice. After HCT, psychosine levels in the brains of 30-day-old twitchers were lowered to 30-35% of values in untreated twitchers, and the levels remained in that range during the post-HCT period. Similarly, brain cerebroside levels remained low in HCT-treated twitcher mice. Although psychosine levels in sciatic nerves of HCT-treated twitcher mice increased more slowly than in the nerves of untreated twitchers, the levels in 100-day-old HCT-treated twitcher mice had reached the same high values as those seen in untreated 40-day-old twitchers. It is not known whether the extremely high levels of psychosine in sciatic nerves ultimately contribute to the death of twitcher mice after HCT.

Aging↗

Occurrence of 2-O-acyl galactosyl ceramide in human and bovine brains.

Ester cerebrosides isolated from whale brain were demonstrated to be a mixture of 6-O-acyl, 2-O-acyl, 4-O-acyl, and 3-O-acyl galactosyl ceramides in that order of content (Yasugi, E., et al. (1982) J. Biochem. 91, 1121-1127). However, the existence of 2-O-acyl and 4-O-acyl galactosyl ceramides has not been reported for other mammalian brains. In the present work, ester cerebrosides isolated from bovine and human brains were examined in order to determine whether the above-mentioned substitution is only present in whale brain or also present in other mammalian brains. For determining the substituted positions of the acyl group on the galactose moiety, free hydroxyl groups of ester cerebrosides were protected with dihydropyran, deacylated by mild alkali treatment, and then subjected to permethylation. Finally, the methylated galactitol acetates obtained by hydrolysis and reduction were analyzed by gas chromatography and gas chromatography/mass spectrometry. By these procedures, ester cerebrosides obtained from bovine and human brains were demonstrated to be not only 6-O-acyl and 3-O-acyl galactosyl ceramides but also 2-O-acyl and 4-O-acyl galactosyl ceramides similar to those of whale brain.

Animals↗

Myelin Membrane: a molecular abnormality.

Myelin was isolated from cerebral white matter from a patient who had died of metachromatic leukodystrophy, and its lipid composition was analyzed. Although the lipid content was nearly normal, the myelin contained a three- to fourfold excess of cerebroside sulfate and a threefold deficiency of cerebroside compared to normal myelin. The deficiency of cerebroside and the excess of cerebroside sulfate may account for defective myelination in this disease.

Amino Alcohols↗

Characteristic distribution of glycolipids in gadoid fish nerve tissues and its bearing on phylogeny.

Glycolipids were isolated from nerve tissues of gadoid fishes including Alaskan pollack and Pacific cod. Their chemical structures were determined by gas-liquid chromatography and gas chromatography-mass spectrometry, and their constituents were analyzed in detail and compared with those of glycolipids from other fish groups. The results revealed that gadoid fish nerve membranes contain peculiar glycolipid molecular species that are distinctly different from those in other teleostean fishes and higher vertebrates. The mole percentage ratio of the four major glycolipids (cerebroside-sulfatide-galactosylglyceride-sulfogalactosylglyce ride) was 48:12:25:15, indicating profound accumulation of glycoglycerolipids. Galactosylglyceride and sulfogalactosylglyceride were primarily of the diacyl type (greater than 90%), the major fatty acids being 16:0 and 18:1. An abundance of glucocerebroside (25 to 55% of cerebroside) and its fatty acid ester (37 to 47% of ester cerebroside) was noted. Cerebroside and sulfatide were characterized by the absence of hydroxy and odd numbered fatty acids, and 24:1 acid was a predominant component of both glucocerebroside and galactocerebroside. Subcellular fractionation revealed that myelin membranes comprised such unusual glycolipid constituents as those seen in whole nerve tissues. A vertebrate whose nerve membranes consist of such peculiar glycolipid molecules has not previously been reported. The characteristics of the glycolipid composition in gadoid fishes are discussed in relation to myelin functions, physicochemical properties of nerve membranes, and the phylogenic significance of this fish group.

Animals↗

[Changes in the levels and composition of glycolipids in various sections of the spinal cord of patients with spinal tuberculosis].

The post mortem content and composition of cerebrosides, sulfocerebrosides and gangliosides found in different sections of the spinal marrow of the healthy persons and 5 patients with spinal tuberculosis were analysed. It was shown that the changes in the content of gangliosides were varying in the lesion focus of different patients. In all patients with chronic tuberculous spondylitis, a significant drop in the content of cerebrosides (myelin markers) and sulfocerebrosides in the lesion focus, as compared with controls, was detected. There were some changes found in the content of cerebrosides and gangliosides in the spinal marrow lesion focus, which are also typical of the disease associated with demyelination of the nervous system. The findings suggest that identification of blood anti-cerebroside antibodies in patients with spinal tuberculosis allows one to make an early diagnosis of abnormalities in the cellular structures of nervous tissue in this form of the disease and to predict its course.

Cerebrosides↗

Globoid cell leukodystrophy (Krabbe's disease): isolation of myelin with normal glycolipid composition.

Myelin was isolated from the brain of a patient with Krabbe's globoid cell leukodystrophy at 0.4% of the normal yield. Despite the exceedingly low yield, the fraction appeared morphologically clean, and consisted mostly of well-preserved myelin lamellae and few contaminating structures. Total lipid and cholesterol were slightly lower than in normal myelin. Total phospholipid was normal, but the ratio of ethanolamine phospholipid to lecithin was reversed. Total galactolipid was normal, and consisted only of cerebroside and sulfatide in normal proportions. The only sugar in cerebroside and sulfatide was galactose. The fatty acid composition of cerebroside and sulfatide was essentially normal with no deficiency of long-chain fatty acids and only with a reversed ratio of C(24:0) to C(24:1) in cerebroside. These data appear to exclude the previous postulate that abnormally rapid breakdown of myelin occurs in this disorder as the result of the formation of chemically abnormal myelin, deficient in sulfatide.

Brain Chemistry↗