Concentration and fatty acid composition of cerebrosides and sulfatides in mature and immature human brain

The fatty acid composition of cerebrosides and sulfatides from frontal lobe gray and white matter was determined for five fresh and four formalinized adult brains and for eight infants. Fatty acid patterns were unaffected by formalinization, but varied considerably from one another in the proportion of saturated to unsaturated fatty acids. The percentages of 24:0 and 24:1 increased with age. Cerebrosides obtained from areas such as the brainstem and cerebellum, where myelination was more advanced, tended to have a larger proportion of long-chain fatty acids than samples extracted from frontal or parietal lobe white matter. Hydroxy fatty acids showed an adult pattern in all instances in which amounts sufficient for accurate quantification could be isolated. Lipid hexose, cerebroside + sulfatide hexose, and methanoleluted hexose were measured in the brains of 12 infants ranging in age from a 4 month fetus to 2 yr. In the most immature, the majority of lipid hexose was in the form of glycolipids more polar than cerebrosides and sulfatides. These have tentatively been identified as hematosides and globosides. With maturation, cerebrosides and sulfatides increased progressively, but the amounts of the more polar glycolipids remained constant in relation to the total lipid content of tissue.     

The Lipid Composition of Urodele Myelin Which Lacks Hydroxycerebroside and Hydroxysulfatide

The concentrations of cerebrosides and sulfatides were measured in the nervous systems of urodeles and related orders with a high performance liquid chromatographic technique. The peripheral and central nervous systems of all three urodele species, Necturus maculosis (mud puppy, a salamander), Notophthalmus viridescens (eastern red spot newt), and Desmognathus ochropheus (mountain salamander), were found to be completely devoid of alpha-hydroxy fatty acid-containing cerebrosides and sulfatides. All species of reptiles and fish classes close to urodeles contain these galactolipids. The levels of nonhydroxy fatty acid-containing cerebrosides and sulfatides are essentially similar in both urodeles and reptiles. Myelin isolated from Necturus spinal cord had a specific density of 1.07, lighter than mammalian myelin. Except for the absence of hydroxycerebrosides and hydroxysulfatides, the lipid composition of Necturus spinal cord myelin is essentially similar to that of frog and rat myelin. The fatty acids of nonhydroxycerebrosides are rich in monounsaturated homologs of C22-C25, and the sphingoid base consists of both sphinganine and sphingosine. Electron microscopic examination of the sciatic nerve showed that the general structure and interlamellar distances of salamander and newt myelin are identical to those of frog, chameleon, and rat. Necturus myelin, therefore, can be used as a model for the study of the functional and structural role of hydroxygalactolipids.     

FATTY ACID COMPOSITION OF CEREBROSIDES IN MICROSOMES AND MYELIN OF MOUSE BRAIN

Abstract— The fatty acid composition of cerebrosides isolated from myelin and from light and heavy microsomes of adult mouse brain was determined. 2-Hydroxy fatty acids represented 80 per cent of the fatty acids in myelin cerebrosides and approximately 55 per cent of the fatty acids in both light and heavy microsomes. In myelin, the majority of the fatty acids, both normal and hydroxy, were of chain length > C-20; in microsomes, shorter chain acids (C-16 to C-20) predominated.     

Lipid Investigation of Central and Peripheral Nervous System in Connatal Pelizaeus-Merzbacher's Disease

Abstract: Brain grey and white matter of a case of Pelizaeus-Merzbacher disease (connatal type Seitelberger) of a 19-month-old boy were analysed with respect to lipids. Cerebrosides and sulfatides were totally absent in the pathological brain. In comparison to control, differences in gangliosides could be detected in grey and white manner. C_18:1, fatty acids were markedly reduced in the main glycerophospholipids of white matter. In sphingomyelin of cortex and white matter 90% of fatty acids were C_18:0; longer chains were absent. In contrast: PNS (nervus fernoralis) lipids contained the main galactolipids. However, these a s well as all other lipid classes showed a 20% reduction compared with values obtained from nervus femoralis of an infant of the same age. The fatty acid patterns of all lipid classes were determined. The only marked deviations from normal were observed in the C₂₄-chains of cere-brosides and sulfatides. The formalin-fixed brain of an older brother (same disease) was analysed only with respect to glycolipids: neither cerebrosides nor sulfatides could be detected.     

Metabolism of cerebrosides and sulfatides in subcellular fractions of developing rat brain

Previous studies on myelinating rat brain indicated that microsomes, Golgi-enriched and cytosol fractions may process galactolipids destined for myelin. To extend these findings we labeled brain galactolipids in vivo and determined the specific radioactivity of cerebrosides and sulfatides in several subcellular fractions. 17-day-old rats were treated by intracranial injection with [14C]galactose 60 min prior to and [3H]galactose 15 min prior to killing. Subcellular fractions were prepared from brain stem, and concentrations of cerebrosides and sulfatides were determined, their radioactivity measured and the 3H/14C ratio compared. Our results showed that the heavier Golgi-enriched fraction (designated Fraction 2) is unique in its low galactolipid content and high specific radioactivities of cerebrosides and sulfatides. The low ratio of the specific activity of cerebroside to that of sulfatide in Fraction 2 compared to other fractions indicates that it may be the site of most rapid conversion of newly synthesized cerebrosides to sulfatides. The specific radioactivities of cerebrosides and sulfatides in cytosol are intermediate between those in Golgi-enriched Fraction 2 and microsomes and those in myelin, consistent with the role postulated for cytoplasmic elements in the transport of cerebrosides and sulfatides to myelin.     

FA2H-dependent fatty acid 2-hydroxylation in postnatal mouse brain

2-Hydroxy fatty acids are relatively minor species of membrane lipids found almost exclusively as N-acyl chains of sphingolipids. In mammals, 2-hydroxy sphingolipids are uniquely abundant in myelin galactosylceramide and sulfatide. Despite the well-documented abundance of 2-hydroxy galactolipids in the nervous system, the enzymatic process of the 2-hydroxylation is not fully understood. To fill this gap, we have identified a human fatty acid 2-hydroxylase gene (FA2H) that is highly expressed in brain. In this report, we test the hypothesis that FA2H is the major fatty acid 2-hydroxylase in mouse brain and that free 2-hydroxy fatty acids are formed as precursors of myelin 2-hydroxy galactolipids. The fatty acid compositions of galactolipids in neonatal mouse brain gradually changed during the course of myelination. The relative ratio of 2-hydroxy versus nonhydroxy galactolipids was very low at 2 days of age ( approximately 8% of total galactolipids) and increased 6- to 8-fold by 30 days of age. During this period, free 2-hydroxy fatty acid levels in mouse brain increased 5- to 9-fold, and their composition was reflected in the fatty acids in galactolipids, consistent with a precursor-product relationship. The changes in free 2-hydroxy fatty acid levels coincided with fatty acid 2-hydroxylase activity and with the upregulation of FA2H expression. Furthermore, mouse brain fatty acid 2-hydroxylase activity was inhibited by anti-FA2H antibodies. Together, these data provide evidence that FA2H is the major fatty acid 2-hydroxylase in brain and that 2-hydroxylation of free fatty acids is the first step in the synthesis of 2-hydroxy galactolipids.     

A method for fractionation of cerebrosides into classes with different fatty acid compositions

A method is described for the separation of beef brain cerebrosides into three fractions containing different classes of fatty acids: nonhydroxy (I), unsaturated nonhydroxy (II), and hydroxy fatty acid cerebrosides (III). The procedure consists of benzoylation of either crude or purified cerebrosides, followed by column chromatographic separation of benzoylated derivatives containing nonhydroxy acids from those containing hydroxy fatty acids. The benzoyl groups are removed by sodium methoxide-catalyzed transesterification; from the reaction mixtures, fractions I and III precipitate. The fraction II present in mother liquor of I was shown to contain mainly short-chain and unsaturated nonhydroxy fatty acid cerebrosides. The fatty acid composition of each fraction was obtained by gas-liquid chromatography.     

An improved procedure for the quantitative determination and characterization of sulfatides in rat kidney and brain by high-performance liquid chromatography

A significant improvement has been made in the desulfation step of our previously published HPLC determination of cerebrosides, sulfatides, and monogalactosyl diacylglycerols (Nonaka, G. and Kishimoto, Y., Biochim. Biophys. Acta 572 (1978) 423-431). Instead of the original two-phase reaction, a solution of trifluoroacetic acid in ethyl acetate is used for the solvolysis in the new method. The revised method was used to determine the levels of cerebrosides and sulfatides in rat kidney. Among four individual glycosphingolipids studied, hydroxysulfatide was present at the highest level (0.7-1.3 nmol/mg of dry tissue), followed by nonhydroxysulfatide (0.3-0.8 nmol/mg of dry tissue). Hydroxycerebroside (0.09-0.16 nmol/mg of dry tissue) and nonhydroxycerebroside (0.03-0.09 nmol/mg of dry tissue) were present in smaller quantities. There appear to be no significant differences between male and female animals of different ages (30-120 days), although the amounts decreased slightly in older animals and there was a higher concentration in female than in male kidney. Tissue size was significantly smaller in females. The homolog composition of rat kidney sulfatide was studied by reverse-phase HPLC, and was found to be significantly different from that reported in human kidney. Rat sulfatides contained fatty acids with a higher degree of saturation and longer chain length. Preliminary studies indicated that rat kidney contained unusually large quantities of C25:1 and C27:1 fatty acids and also that there was more C26:1 than C24:1 acid. In brain of the same animals the ratio of nonhydroxy to hydroxysulfatide decreased with age (1.5:1 in 30-day-old brain; 1:1 at 90 days).     

Ceramide Synthesis from Free Fatty Acids in Rat Brain: Function of NADPH and Substrate Specificity

At the subcellular level, the synthesis of ceramide from free lignoceric acid and sphingosine in brain required reconstituted enzyme system (particulate fraction, heat-stable and heat-labile factors) and pyridine nucleotide (NADPH). The mitochondrial electron transfer inhibitors (KCN and antimycin A), energy uncouplers (oligomycin and 2,4-dinitrophenol), and carboxyatractyloside, which prevents the transport of ATP and ADP through the mitochondrial wall, inhibit the synthesis of ceramide in the presence of NADPH but have very little effect in the presence of ATP. Similar to the synthesis of ceramide, the synthesis of ATP from NADPH and NADH by the particulate fraction also required cytoplasmic factors (heat-stable and heat-labile factors). Moreover, ATP, but not its analog (AMP-CH2-P-O-P), can replace NADPH, thus suggesting that the function of the pyridine nucleotide is to provide ATP for the synthesis of ceramide. The cytoplasmic factors were not required for the synthesis of ceramide in the presence of ATP. The maximum velocity for synthesis of ceramide from free fatty acids of different chain lengths (C16-C26) was bimodal, with maxima around stearic acid (C18) and behenic acid (C22). The relative rate of synthesis of ceramide parallels the relative distribution of these fatty acids in brain cerebrosides and sulfatides.     

FA2H is responsible for the formation of 2-hydroxy galactolipids in peripheral nervous system myelin

Myelin in the mammalian nervous system has a high concentration of galactolipids [galactosylceramide (GalCer) and sulfatide] with 2-hydroxy fatty acids. We recently reported that fatty acid 2-hydroxylase (FA2H), encoded by the FA2H gene, is the major fatty acid 2-hydroxylase in the mouse brain. In this report, we show that FA2H also plays a major role in the formation of 2-hydroxy galactolipids in the peripheral nervous system. FA2H mRNA and FA2H activity in the neonatal rat sciatic nerve increased rapidly during developmental myelination. The contents of 2-hydroxy fatty acids were approximately 5% of total galactolipid fatty acids at 4 days of age and increased to 60% in GalCer and to 35% in sulfatides at 60 days of age. The chain length of galactolipid fatty acids also increased significantly during myelination. FA2H expression in cultured rat Schwann cells was highly increased in response to dibutyryl cyclic AMP, which stimulates Schwann cell differentiation and upregulates myelin genes, such as UDP-galactose:ceramide galactosyltransferase and protein zero. These observations indicate that FA2H is a myelination-associated gene. FA2H-directed RNA interference (RNAi) by short-hairpin RNA expression resulted in a reduction of cellular 2-hydroxy fatty acids and 2-hydroxy GalCer in D6P2T Schwannoma cells, providing direct evidence that FA2H-dependent fatty acid 2-hydroxylation is required for the formation of 2-hydroxy galactolipids in peripheral nerve myelin. Interestingly, FA2H-directed RNAi enhanced the migration of D6P2T cells, suggesting that, in addition to their structural role in myelin, 2-hydroxy lipids may greatly influence the migratory properties of Schwann cells.     

The lipid composition of the electric organ of the ray, Torpedo marmorata, with specific reference to sulfatides and Na+-K+-ATPase.

The lipids from the electric organ of the ray, Torpedo marmorata, have been isolated and characterized. The major lipids were cholesterol, choline phospholipids, ethanolamine phospholipids, and sphingomyelins. The major fatty acids of ethanolamine phospholipids were 18:1, 18:0, 22:6, and 20:4. More than 50% of the acids in choline phospholipids were 16:0. The sphingomyelins consisted of five major ceramide species, all with sphingosine and the fatty acids 14:0, 15:0, 16:0, 22:1, and 24:1. The fatty acid 15:0 was mostly branched (n-2), a fatty acid earlier identified in sphingomyelins of the rectal gland of spiny dogfish. All long-chain bases were dihydroxy bases with a small percentage of branched chains. Sulfatides (cerebroside sulfate) made up the largest glycolipid fraction. The polar moiety wase galactose-3-sulfate. The fatty acids were normal and 2-hydroxy; the homologue 24:1 was the most abundant in both types of fatty acids. Most fatty acids were higher homologues of mono-unsaturated acids, but normal 18:0 fatty acid was also found. The long-chain bases were both dihydroxy and trihydroxy, with very small amounts of branched chains. The two major ceramide species of sulfatides were sphingosine combined with normal and hydroxy 24:1 fatty acids, respectively. Smaller amounts of trihydroxy base (18:0) were found linked to hydroxy 24:1 fatty acid, but not to its normal homologue. The cerebrosides contained the two major species mentioned above but lacked the trihydroxy base-hydroxy fatty acid species. The ratio of the activity of Na+-K+-dependent ATPase (EC 3.6.1.3) and the concentration of sulfatides was similar to ratios found for other tissues with normal and increased Na+ and K+ transporting capacity. The significance of this finding is discussed.     

THE DISTRIBUTION AND BIOSYNTHESIS OF THE MYELIN -GALACTOLIPIDS IN THE SUBCELLULAR FRACTIONS OF BRAINS OF QUAKING AND NORMAL MICE DURING DEVELOPMENT

Abstract— The biosynthesis and accumulation of monogalactosyl diglyceride, galacto-cerebrosides and sulfatides were studied in the brain of quaking mouse during myelination. The specific activity of monogalactosyl diglyceride synthesis of the mutant mouse was reduced to 50% of the control of the same age, comparable to the reduction in the biosynthesis of galactosylcerebrosides and sulfatides. The three galactolipids were largely associated with the myelin and microsomal fractions in the normal and quaking mice at the ages studied. Although the concentrations of microsomal galactolipids (expressed as nmol/g wet wt of brain) were lower in quaking mice than in the controls at all ages, the percentage of total brain monogalactosyl diglyceride recovered in the microsomes of the mutant mouse was always larger than in the microsomes of the controls. Between 16 and 41 days, the monogalactosyl diglyceride content of the control myelin increased 10-fold, whereas the concentrations in the mutant increased only 2-fold. In normal animals, the percentage of total myelin galactolipids in the 'small myelin' decreased over the age of 1841 days with concomitant increase in the 'large myelin'. In contrast, in the mutant, large percentages of these compounds remained associated with the small myelin even at late periods of myelin development. These findings indicate that the slow rate of deposition of myelin in the brain of quaking mouse may be due to a defective transport mechanism of the galactolipids from the site of synthesis (microsomes) to the site of deposition (myelin), or to a defect in the mechanism of final myelin assembly, rather than to a lipid-specific genetic error.     

Reptile brain cerebrosides and cerebroside sulfates

Studies have been made on the content of cerebrosides and cerebroside sulfates, as well as on their fatty acid composition in the brain of reptiles, subclass Anapsida (tortoises Emys orbicularis and Testudo horsfieldi) and subclass Lepidosauria (lizards Agama caucasica, A. sanguinolenta, Phrynocephalus mystaceus and snake Natrix tesselata). Total content of cerebrosides and cerebroside sulfates is higher in the brain of Lepidosaurians than in that of Anapsids. In the brain of tortoises, the content of cerebroside fraction with hydroxy fatty acids is significantly higher than of the fraction with normal fatty acids, which is also typical of the brain of homoiothermic mammals and birds. In the brain of Lepidosaurians, concentration of hydroxycerebrosides is considerably lower than of cerebrosides with normal fatty acids, which is similar to lower vertebrates -- amphibians and fishes. Low content of hydroxycerebrosides was found in all the Lepidosaurians investigated, irrespectively of their ecological conditions, being therefore dependent on their phylogenetic position. The composition of fatty acids, both normal and hydroxyderivates, as well as that of glycolipids from the brain of Anapsids and Lepidosaurians is essentially similar. However, some interspecific differences were noted in the pattern of fatty acids of cerebrosides and cerebroside sulfates of the brain, which concern the content of saturated and long chain fatty acids.     

Brain lipid biochemistry of the sturgeons Acipenseridae]

Brain lipids of 4 species of sturgeons-Acipenser güldenst?dti, A. stellatus, A. ruthenus and Huso huso-have been investigated. In whole brain homogenates the content of the basic phospholipid families, their fatty acid composition as well as the content of glycosphingolipids-gangliosides, cerebrosides and sulfatides were studied. The quantitative relations between different molecular ganglioside fractions and their fatty acid composition, as well as the relative content of hydroxycerebrosides and cerebrosides with normal fatty acids were determined. The brain lipids of Acipenseridae were compared to previously obtained data on the brain of Elasmobranch and Teleost fishes. The brain lipid pattern of the four sturgeon species is very similar, but it differs greatly from that of Elasmobranch and of Teleostean brain, being in some respect more like the type of bony fish brain, in others the kind of brain of sharks and rays, and frequently considerably differing from both these types. The conspicous peculiarity in the content and molecular characteristics of the brain lipids of Acipenseridae compels us to agree with the opinion expressed by the late A.N. Belozerski and his coworkers [26, 27], based on a detailed study of fish DNA nucleotides, that the Ganoid fish are to be regarded as an independent class.     

Changes in fatty acid composition of human brain myelin lipids during maturation

Abstract— The variation with age of the fatty acid composition of the major lipids in human brain myelin was compared with that of cerebral white matter from the same region. The myelin was isolated from the semiovale centre of the cerebrum of 27 subjects neonatal to old aged. The phospholipid, cholesterol and galactolipid concentrations were determined in all the samples, as were the proportions of the major phospholipid classes. The proportions of cholesterol and especially of the galactolipids increased in myelin during the first 6 months, and in cerebral white matter up to 2 years. During this period the individual phospholipids also varied substantially. Serine phosphoglycerides and especially sphingomyelins increased, and choline phosphoglycerides decreased. The fatty acid patterns of ethanolamine phosphoglycerides (EPG) and sphingomyelins underwent the largest changes. The proportions of saturated fatty acids in EPG diminished rapidly, and there was an increase of monoenoic acids. Fatty acids of the linoleic acid series showed a peak between 4 and 12 months, after which time their proportion slowly diminished to old age. The major fatty acid of this series was docosatetraenoic acid, 22:4 (n-6), which constituted more than 25% of total fatty acids at the maximum level. The fatty acid changes were larger in cerebral white matter, but from 2 years of age the EPG fatty acid pattern in myelin was similar to that in white matter. The fatty acid changes in serine and choline phosphoglycerides of myelin with maturation were much less striking than in EPG but of a similar type. In myelin sphingomyelin the proportion of saturated long-chain fatty acids, C₁₆-C₂₂, diminished, while that of monoenoic acids increased and continued to do so up to old age. From 2 years of age the fatty acid patterns in myelin and cerebral white matter were quite similar. Also the fatty acid patterns of cerebrosides and sulphatides in cerebral white matter and myelin were the same except for the first 2 months of life. The same fatty acid changes occurred in cerebrosides and sulphatides as in the sphingomyelins, i.e. increased proportions of unsaturated (monoenoic) acids. The proportions of 24:1 and 24h:1 and of the odd-numbered fatty acids 25:1 and 23h:1 continued to increase to old age. The variations of the individual lipid fatty acid patterns were small except in the youngest age classes, in which the variations were presumably ascribable to the difficulty in determining the gestational age.     

Lipid composition and sphingolipid fatty acids of myelin in fruit bat brain

Myelin was isolated from the brain of adult fruit bats (Rousettus aegyptiacus) in a discontinuous sucrose gradient. Cholesterol comprised 189.0 mol/100 mol lipid phosphorus, galactolipids 60.3 mol/100 mol phosphorus and plasmalogens 32.5 mol/100 mol phosphorus. Choline and ethanolamine glycerophosphatide were present in nearly equal amounts followed by serine glycerophosphatide, sphingomyelin and inositol glycerophosphatides.The fatty acid composition of sphingomyelin and non-hydroxy cerebroside was determined by gas-liquid chromatography. Fatty acids were mainly saturated or mono-unsaturated with a small percentage of polyunsaturated fatty acids present.The lipid composition and sphingolipid fatty acid distribution in bat myelin was fairly similar to that of other species.     

Branched long chain bases in cerebrosides of the guinea pig Harderian gland

Cerebrosides obtained from the guinea pig Harderian gland were analyzed. The purified cerebrosides gave a single spot on thin-layer chromatography, the Rf value being similar to that of phrenosine obtained from whale brain. The cerebrosides consisted of 74.7% of glucosylceramide and 25.3% of galactosylceramide. The fatty acid composition of these cerebrosides was 0.7% of non-hydroxy fatty acids and 99.3% of alpha-hydroxy fatty acids. Among these alpha-hydroxy fatty acids, a small amount of methyl branched acids was detected. The substituted position of methyl branching of alpha-hydroxy fatty acids was the 16th carbon atom from the carboxyl end irrespective of the carbon chain length. The long chain bases were composed of sphinganine (78%) and sphingenine (22%). 4-D-Hydroxysphinganine was not found. The most remarkable feature of the long chain bases of cerebrosides in the Harderian gland was the presence of a large amount of methyl branched sphinganine. The cerebrosides obtained from the cerebrum and cerebellum of the same animal were also analyzed. The sugar, fatty acid, and long chain base compositions of these cerebrosides were similar to those of whale brain cerebrosides. Methyl branched sphinganine was not found in guinea pig brain.     

Triethyllead treatment of cultured brain cells

Cultured cells from chick embryo brains were studied for their sensitivity to triethyllead. Triethyllead chloride (3.16 M) was added to the nutrient medium and incubated for 48 hr with the cells. Morphological changes in light microscope and radioactive labeling of galactolipids were assayed. Triethyllead treatment reduced the number of neuronal cells with processes. Morphological changes were not observed in glial cells. The [³⁵S]sulfate labeling of sulfatides was reduced to 50%. The [³H]serine labeling of cerebrosides with alpha-hydroxy fatty acids was not influenced, while the [³H]serine labeling of cerebrosides with nonhydroxy fatty acids was inhibited 40% in one- and two- but not in three-week-old cultures. The results indicate that the nerve cell response to triethyllead in cultures is selective, since the neurons are more sensitive than the glia cells and the labeling of sulfatides is more sensitive than that of cerebrosides.     

DHPOSITION OF LIPIDS IN THE DEVELOPING CENTRAL AND PERIPHERAL NERVOUS SYSTEMS OF THE CHICKEN

Abstract— The lipid composition of chick brain and sciatic nerve was determined during development. It was confirmed that the addition of CaCl₂ to solvents during the extraction of lipids from brain results in much higher yields of diphosphoinositides particularly from unmyelinated embryo brain. Unlike the earlier report for rat brain, the recovery of triphosphoinositides was also Substantially increased. The amount of CaCl₂, required to achieve optimal recoveries decreased with increasing age and addition of more than this optimal amount depressed the yields of polyphosphoinositides, particularly triphosphoinositides. CaCl₂, addition did not improve the yield of diphosphoinositides from sciatic nerve of any age but drastically reduced recovery of triphosphoinositidcs. Differenccs in the effect of CaCl₂ were not the result of variation in the tissue concentrations of calcium or magnesium.
The lipid composition of sciatic nerve closely reflected that of the myelin. Both polyphosphoinositides were absent initially and their accumulation paralleled that of cerebrosides and sulfatides. The concentration of diphosphoinositides remained constant after the period of most active myelination while triphosphoinositides and the galactolipids continued to increase suggesting maturational changes in the myelin composition. The pattern of deposition in chick brain was similar except for the much greater contribution of non-myelin structures. Both polyphosphoinositides were present in equimolar amounts in pre-myelination embryonic tissue. The concentration of diphosphoinositides increased during active myelination only while triphosphoinositides continued to increase thereafter.     

FATTY ACID COMPOSITION OF CEREBROSIDES, SULPHATIDES AND CERAMIDES IN MURINE SUDANOPHILIC LEUCODYSTROPHY: THE JIMPY MUTANT

The fatty acid composition of cerebrosides, sulphatides and ceramides was determined at 15-16 days post partum in the brain of the Jimpy mutant and in littermate controls. There was a marked deficit in the long chain fatty acids (C₂₂-C₂₄) of cerebrosides and sulphatides of Jimpy brain, with the unsubstituted fatty acids affected more than the alpha-hydroxy fatty acids. A decrease of long chain normal fatty acids was also found in the ceramides of Jimpy brain. The deficit of long chain fatty acids in these sphingolipids of the Jimpy brain was more severe than that found in the Quaking mutant which has a less extensive disorder of myelin formation.