IN VIVO METABOLISM OF [G-3H]LIGNOCERIC ACID IN DEVELOPING RAT BRAIN1

Abstract— [G-³H]Lignoceric acid (tetracosanoic acid) was injected into the brains of 20-day-old rats, and the animals were killed after 8, 24, or 72 h. Various lipids were isolated from these brains, and the distribution of radioactivity was determined. The injected free acid rapidly disappeared, and the radioactivity was incorporated into varying chain-length nonhydroxy- and hydroxy saturated fatty acids of sphingolipids and phospholipids. Little radioactivity was found in unsaturated acids, sphingo-sine, and cholesterol. A time-dependent shift of the label among various fatty acids was relatively small 8 h after injection, probably because of the metabolic stability of the brain sphingolipids. In cerebrosides, the radioactivity was equally distributed between nonhydroxy and x-hydroxy fatty acids of all chain lengths. C₂₃ and C₂₂ fatty acids contained equal total radioactivities; C₂₃ and C₂₄ fatty acids contained similar specific activities. These results confirm the significant role of a-hydroxylation and 2-oxidation in the synthesis of very long-chain fatty acids in brain. In total lipid fatty acids, docosanoic acid (22:0) contained more radioactivity than its α-oxidation precursor, α-hydroxytricosanoic acid (23h:0) at all times. In sphingolipid fatty acids, the specific activity of 21:0 was always higher than that of its ct-oxidation precursor 22:0. These observations indicate that part of the 22:0 and 21:0 was derived by β-oxidation from the injected lignoceric acid or its α-oxidation product, respectively.     

The effect of carnitine on the oxidation of saturated fatty acids by pea cotyledon mitochondria

Summary Carnitine was found to stimulate fatty acid oxidation by pea (Pisum sativum L.) cotyledon mitochondria. The stimulation was at a maximum for long chain (C_16:0) and short chain (C_4:0 and C_6:0) fatty acids. Evidence was also provided which indicated that mid-chain (C_10:0 and C_12:0) fatty acid oxidation by mitochondria was stimulated by carnitine. It is postulated that carnitine acts by facilitating transport of these species of fatty acids across the mitochondrial membranes to intramitochondrial -oxidation sites.Abbreviations ADP adenosine-5¹-diphosphate - ATP adenosine-5¹-triphosphate - BSA bovine serum albumin - CoA coenzyme A - EDTA ethylenediamine tetra-acetate - RCR respiratory control ratio     

Distribution of C22-, C24- and C26-α-Unit-Containing Mycolic Acid Homologues in Mycobacteria

There are three mycolic acid homologues with C₂₂-, C₂₄- and C₂₆-α-units in Mycobacterium. In order to reveal the composition and distribution of these homologues in each subclass and molecular species of mycolic acids and to compare them with the composition of constitutive non-polar fatty acids (free and bound forms), we have separated non-polar fatty acids and each subclass of mycolic acids from 21 mycobacterial species by thin-layer chromatography, and analyzed non-polar fatty acid methyl esters by gas chromatography (GC) and the cleavage products of methyl mycolate by pyrolysis GC. We further performed mass chromatographic analysis of trimethylsilyl (TMS) ether derivatives of mycolic acid methyl esters by monitoring [B-29]⁺ ions (loss of CHO from the α-branched-chain structure of mycolic acids) of m/z 426, 454 and 482 which are attributed to C₂₂-, C₂₄- and C₂₆-α-units of TMS ether derivatives of methyl mycolates, respectively, (Kaneda, K. et al, J. Clin. Microbiol. 24: 1060-1070, 1986). By pyrolysis GC, C_22:0, C_24:0 and C_26:0 fatty acid methyl esters generated by the C₂-C₃ cleavage of C₂₂-, C₂₄- and C₂₆-α-unit-containing mycolic acid methyl esters, respectively, were detected. Their proportion was almost the same among subclasses of mycolic acids in every Mycobacterium and also similar to the proportion of constitutive non-polar C_22:0, C_24:0 and C_26:0 fatty acids. By mass chromatography, the composition and distribution of C₂₂- and C₂₄-α-unit-containing homologues were revealed to be similar between α- and α'-mycolic acids in every Mycobacterium. We further analyzed in detail M. vaccae and demonstrated that the mass chromatogram of C₂₂-α-unit-containing homologue was analogous in shape to that of the C₂₄-α-unit-containing one, with the latter mass chromatogram being up-shifted from the former by two carbon numbers, in every subclass of α-, α'-, keto and dicarboxy mycolic acids. The present study suggests that the compositions of three homologues of both mycolic acids and constitutive non-polar fatty acids, which are characteristic to each mycobacterial species, may reflect the proportion of the amount of free C_22:0, C_24:0 and C_26:0 fatty acids synthesized in the cell. It is further demonstrated that intermolecular condensation of two fatty acids which become α- and β-units of mycolic acids will occur independently of the carbon chain length or kinds of polar moieties of fatty acids.     

Cellular fatty acid composition ofCorallococcus coralloides

The fatty acid composition of five strains ofCorallococcus coralloides and three reference species ofMyxococcus were determined by gas-liquid chromatography. Methyl esters of fatty acid containing from 12 to 22 carbon atoms were identified. The major fatty acids present were C₁₅ and C₁₇ saturated branched chain, and both C₁₆ saturated and unsaturated straight chain acids. The C₁₇ saturated branched and straight chain acids, which were in valuable concentration in species ofMyxococcus, were not, however, detected in all strains ofC. coralloides. The application of these results in the distinction ofC. coralloides from the genusMyxococcus is discussed.     

Ultrastructure and lipid chemistry of specialized epidermal structure of Indian porcupines and hedgehog

Poddar‐Sarkar, M., Raha, P., Bhar, R., Chakraborty, A. and Brahmachary, R.L. 2011. Ultrastructure and lipid chemistry of specialized epidermal structure of Indian porcupines and hedgehog. —Acta Zoologica (Stockholm) 92 : 134–140. In the present study, we investigated the ultrastructural variations of specialized epidermal structure of Indian porcupines (Hystrix indica and Atherurus macrourus) and hedgehog (Hemiechinus collaris) as well as the variation in the fatty acid composition of total lipid fraction. Scanning electron microscope images reveal the usual scaly structure in surface view and network of channels in cross‐section but with different orientation of partition walls. The lipid profile reveals the presence of free sterol, long‐chain alcohol, free fatty acids, wax ester and sterol ester in all the three cases and trace amount of triglyceride, diglyceride and monoglyceride. Gas chromatography–mass spectrometry analysis of fatty acid methyl ester of total lipid fraction indicates the presence of C₈‐C₂₂ fatty acids in Hystrix indica, C₈‐C₁₈ in Atherurus macrourus and C₈‐C₂₀ fatty acids in Hemiechinus collaris. It is interesting to note that the total lipid fraction of hedgehog shows no branched‐chain, unsaturated and odd‐carbon fatty acids. Odd‐carbon fatty acid and branched‐chain fatty acids detected in the adult H. indica but were absent in juvenile H. indica as well as in A. macrourus. With the exception of C_18:1, the other unsaturated fatty acids were also absent in both juvenile H. indica and A. macrourus.     

Chain elongation of fatty acid in brain: a comparison of mitochondrial and microsomal enzyme activities

The activities of mitochondrial and microsomal fatty acid-elongating enzymes have been measured in rat brain during postnatal development and in brains of jimpy, msd, and quaking mice. The microsomal enzyme activity rose from a low in the immature brain to a maximum at 21 days of age and then declined to low levels in the mature brain. The developmental patterns were similar for all acyl-CoAs tested. The maximum activity fell sharply from C₁₆ to C₁₈ and then fell gradually with increase in fatty acid chain length up to C₂₄. The activities for monounsaturated acyl-CoAs were slightly higher than for corresponding saturated esters. The mitochondrial enzyme activity was high in the immature brain and remained virtually unchanged during further brain development. This activity steadily decreased with increasing chain length from C₁₆ to C₂₄. The microsomal enzyme activity was reduced in myelin-deficient mutants compared to their controls. The extent of reduction was most severe for C₂₀- to C₂₄-CoAs followed by C₁₈-CoA and then C₁₆-CoA, for which the activity was reduced only in the jimpy mouse. The activities for C₂₀- to C₂₄-CoAs in jimpy, msd, and quaking mice were 12, 38, and 52% of the control, respectively. The mitochondrial enzyme activity was not affected by these mutations. Fatty acid synthetase activity was similar in the mutant and control mice. These results suggest that the deficiency of long-chain fatty acids in the central nervous system of myelin-deficient mouse mutants is due to reduced synthesis by the microsomal enzyme, which is directly related to myelination. The brain mitochondrial enzyme appears to be unrelated to myelination.     

Differences in cellular fatty acids and lipid composition inClostridium pasteurianum under nitrogen-and non-nitrogen-fixing conditions

Clostridium pasteurianum total cellular saturated fatty acids increased through its growth cycle from 81% to 91% but varied significantly in the composition under nitrogen- and non-nitrogen-fixing conditions. During ammonia-assimilating growth, palmitic acid decreased from 67.7% to 43.5% by late log while marked increases in shorter chain saturated fatty acids (C_15:0 and below) and a long chain saturated C_22:0 occured. In contrast, under N₂-fixing growth conditions, palmitic acid increased from 45.5% to 84.3% by late log, representing nearly the total amound of saturated fatty acids found inC. pasteurianum. The total cellular lipid concentration decreased as the culture aged. irrespective of the nitrogen sources; however, the phospholipid concentration increased significantly during N₂-fixing growth as compared with a 50% decrease during ammonia-assimilating conditions. The implication of these differences and possible role of palmitic acid and phospholipids inC. pasteurianum nitrogen fixation process are discussed.     

Microbial fatty acid specificity

Strains ofRhodotorula sp.,Candida spp. andLangermania sp. cultivated on polyunsaturated oil preferentially incorporated more unsaturated fatty acids. These fatty acids were used mainly for growth needs whereas the saturated ones accumulated in the microbial cell. The cellular oil and the remaining oil in the culture had a lower degree of unsaturation as compared to the initial oil, and a modified fatty acid composition.Candida lipolytica, in a chemostat continuous culture, incorporated C₁₈ fatty acids in the order of C_18:3>C_18:2>C_18:1>C_18:0, and accumulated mostly the saturated ones. The specific productivity of the cellular oil and of the oil remaining in the culture medium was 0.036 and 0.487 gg⁻¹ h⁻¹, respectively, at dilution rateD=0.2/h.     

Studies on essential fatty acid deficiency. Effect of the deficiency on the lipids in liver mitochondria and oxidative phosphorylation

1. Dietary deficiency of essential fatty acids results in a twofold increase in the neutral lipid content of liver mitochondria as compared with the corresponding value for stock-fed rats. 2. Deficiency produces changes in the pattern of the constituent fatty acids of the main phospholipid fractions of liver mitochondria which are similar to those previously reported for the lipids of whole liver. There is a fall in the content of C_18:2 acid and to a smaller extent of C_20:4 acid associated with a rise of C_16:1, C_18:1 and C_20:3 acids. 3. Deficiency results in small decreases in the phosphorylation quotients of liver mitochondria during oxidation of succinate and pyruvate, but the values lie within the range reported for normal mitochondria. Mitochondrial respiration with succinate is decreased as a result of deficiency but no change was observed with pyruvate as substrate.     

Two forms of Ca2+-dependent cyclic 3':5'-nucleotide phosphodiesterase from human aorta and effect of free fatty acids.

Investigations were carried out on two DEAE-cellulose columnresolvable Ca²⁺-dependent nucleotide 3′:5′-phosphodiesterases from human aorta. An extract from human aorta when chromatographed on DEAE-cellulose yielded five active cyclic nucleotide 3′:5′-phosphodiesterase fractions designated as F I, F II, F III, F IV, and F V and these fractions eluted at about 0.02, 0.08, 0.18, 0.28, and 0.38 M sodium acetate. F 111 and F IV were found to be activated by a protein modulator and free fatty acids. The two Ca²⁺-dependent cyclic nucleotide phosphodiesterases (F III and FIV) were clearly separated by rechromatography on DEAE-cellulose column and were found to hydrolyze guanosine 3′:5′-monophosphate (cyclic GMP) preferentially. Fatty acids as well as a protein modulator increased the maximum velocity of one form (F III) without affecting the K_m values and decreased the K_m values of the other (F IV) without changing maximum velocity. The extent of maximum stimulation by behenic acid (C₂₂) and a protein modulator was similar at optimal conditions. Fatty acids did not require calcium for stimulation of the phosphodiesterases. Stimulating activity diminished as the hydrocarbon chain length of the fatty acid was shortened or when more than two unsaturated bonds were introduced. Behenic acid (C₂₂) and eruic acid (C_22:1) were the most potent stimulators among the saturated or unsaturated fatty acids tested. The other DEAE-cellulose-resolvable aortic phosphodiesterase forms (F I, FII, and F V) were neither activated by the protein modulator nor stimulated significantly by fatty acids.     

Protein deficiency and age related alterations in rat peritoneal macrophage lipids

The effects of dietary protein restriction and age on the thioglycollate elicited peritoneal macrophage lipid constituents were studied. Impact of subtle changes in lipid components on macrophage functions have been assessed. Lipid profiles of macrophages recovered from rats fed 20 and 4% protein diets and stock diet fed rats (0 and 3 wk) were comparable qualitatively. Quantitative analysis however revealed significant decrease in phospholipids (30–40%) and consequent elevation of cholesterol/phospholipid molar ratios in the protein depleted and young rats (0 wk), compared to the protein fed groups. The protein deficient and the young rats also exhibited accumulation of certain neutral lipids and reduction in triglycerides. Analysis of fatty acid methyl esters of macrophage phospholipids revealed the predominance of long chain polyunsaturated fatty acids even when oleic (C_18:1) and linoleic (C_18:2) formed the bulk of unsaturated fatty acids in the diet. However, the long chain poly unsaturated fatty acid content, particularly the docosahexaenoic acid (C_22:6n-3) was greatly reduced in the protein depleted and 0 wk rats. Observed changes in the long chain polyunsaturated fatty acids of macrophage phospholipids may be of physiological significance as they modulate the immunological functions of the cell.     

FATTY ACID ABNORMALITY IN ADRENOLEUKODYSTROPHY

—Recent clinical and morphological evidence established that adrenoleukodystrophy is a distinct X-linked genetic disorder. Fatty acid compositions of lipids in the brain, adrenal and serum from seven patients were examined. Cholesterol esters of both brain and adrenal contained substantial proportions of fatty acids longer than C₂₂ (11.8–41.9% of total in the brain and 13.4-34.8% of total in the adrenal), while cholesterol esters from normal and pathological control specimens contained very little. These very long chain fatty acids were generally saturated in brain cholesterol esters but significant amounts of unsaturated long chain fatty acids were also present in adrenal cholesterol esters. The long chain fatty acids showed bell-shaped distribution with C₂₅ or C₂₆ at the peak. Ganglio-sides from patients’white matter also showed increased proportions of very long-chain fatty acids, up to 50% of the total. Qualitatively similar but much milder fatty acid abnormalities were also found in galactosylceramide of the brain. On the other hand, fatty acids and fatty aldehydes of brain glycerophospholipids, adrenal free fatty acids, triglycerides and glycerophospholipids were not abnormal. Furthermore, serum cholesterol esters from two patients did not show the long-chain fatty acid abnormality found in brain and adrenal cholesterol esters. Sequential extractions with acetone and hexane established that the characteristic birefringent material in the brain and adrenal is indeed cholesterol esters with very long chain fatty acids. This type of fatty acid abnormality has not been described in other pathological conditions and may well represent the unique biochemical abnormality that is directly related to the fundamental genetic defect underlying adrenoleukodystrophy.     

In vitro synthesis of mycolic acids by the fluffy layer fraction of Bacterionema matruchotii

Biosynthetic activity for mycolic acid occurred in the fluffy layer fraction but not in the 5000g supernatant of Bacterionema matruchotii. With [1-¹⁴C]palmitic acid as precursor for the in vitro system, the predominant product was identified as C_32:0 mycolic acid by radio-gas-liquid chromatographie (radio-GLC) and gas chromatographic/mass spectroscopic analyses; if [1-¹⁴C]stearic acid was used, two major radioactive peaks appeared on GLC: one corresponding to the peak of (C_34:0 + C_34:1) mycolic acids and the other to (C_36:0 + C_36:1) mycolic acids. By pyrolysis/radio-GLC analysis, C_32:0 mycolic acid synthesized by [1-¹⁴C]palmitic acid was pyrolyzed at 300 °C to form palmitaldehyde (the mero moiety) and methyl palmitate (the branch moiety). The pH optimum for the incorporation of [1-¹⁴C]palmitate into bacterionema mycolic acids was 6.4 and the reaction required a divalent cation. The in vitro system utilized myristic, palmitic, stearic and oleic acids (probably via their activated forms) well as precursors, among which myristic and palmitic acids were more effective than the rest. Avidin showed no effect on the biosynthesis of mycolic acid from ¹⁴C-palmitate whereas cerulenin, a specific inhibitor of β-ketoacyl synthetase in de novo fatty acid synthesis, inhibited the reaction at a relatively higher concentration. Thin-layer chromatographic analysis of lipids extracted from the reacting mixture without alkaline hydrolysis showed that both exogenous [1-¹⁴] fatty acid and synthesized mycolic acids were bound to an unknown compound by an alkali-labile linkage and this association seemed to occur prior to the condensation of two molecules of fatty acid.     

The distribution of fatty acids including petroselinic and tariric acids in the fruit and seed oils of the Pittosporaceae, Araliaceae, Umbelliferae, Simarubaceae and Rutaceae

The fatty acid composition of the fruit oils or seed oils of Pittosporaceae (eight genera, 10 species), Araliaceae (two species), Simarubaceae (three species), and of one umbelliferous and one rutaceous species were determined by gas chromatography, argentation TLC and ozonolysis. In the Pittosporaceae, in which the major C₁₈ fatty acid of all species was either oleic acid (18:1, 9c) or linoleic acid (18:2, 9c, 12c), large amounts of C₂₀ and C₂₂ fatty acids seem to occur regularly. Petroselinic (18:1, 6c) and tariric (18:1, 6a) acids were absent. However, petroselinic acid was the major fatty acid in the Araliaceae and Umbelliferae. In these two families only small amounts of C₂₀ and C₂₂ acids were detected and tariric acid was absent. The Rutales contained relatively high amounts of trans-octadecenoic acids (18:1, 9t). Tariric acid was the major fatty acid in the two species of Picramnia (Simarubraceae), which also contained small amounts of petroselinic acid. The major fatty acids in Ailanthus glandulosa (Simarubaceae) and Phellodendron amurense (Rutaceae) were linoleic or linolenic acid (18:3, 9c, 12c, 15c); these species contained neither tariric nor petroselinic acid and the levels of C₂₀ and C₂₂ fatty acids were low. The appearance of schizogenous resin canals and polyacetylenes and the absence of iridoids and petroselinic acid allows the Pittosporaceae to be separated from the Rutales and Araliales and to be placed in an independent order, the Pittosporales. Arguments for a rather close relationship of the Pittosporales to the Araliales and Cornales (including the Escalloniaceae) are presented.     

Fatty acids and aldehydes of brain phospholipids during fetal and infant development in man

Abstract— Brains of human fetuses III, V, VI, VII months) newborn and infants (3, 7 and 13 months old) were investigated and the contents of total lipid, neutral- and phospholipid fractions were estimated. Fatty acids as well as fatty aldehydes of the phosphatides were analysed by gas chromatography. The results showed, that during this period of development the C₁₆-compounds in the fatty acid and aldehyde fractions decrease, while the total C₁₈-derivatives increase. However, the C₁₈-monoenoic fatty acids decrease from the third fetal month until birth and increase during myelination. The same pattern was found for the C₁₈-monoenoic aldehydes. The amounts of C₂₀- and C₂₂-polyenoic fatty acids were relatively constant. Only trace amounts of aldehydes with chain lengths other than C₁₆- and C₁₈-saturated and C₁₈-monoenoic comnniinds were found.     

Biosynthesis of C(20) and C(22) Fatty Acids by Developing Seeds of Limnanthes alba: CHAIN ELONGATION AND Delta5 DESATURATION

The storage triacylglycerols of meadowfoam (Limnanthes alba) seeds are composed essentially of C₂₀ and C₂₂ fatty acids, which contain an unusual Δ5 double bond. When [1-¹⁴C]acetate was incubated with developing seed slices, ¹⁴C-labeled fatty acids were synthesized with a distribution similar to the endogenous fatty acid profile. The major labeled product was cis-5-eicosenoate, with smaller amounts of palmitate, stearate, oleate, cis-5-octadecenoate, eicosanoate, cis-11-eicosenoate, docosanoate, cis-5-docosenoate, cis-13-docosenoate, and cis-5,cis-13-docosadienoate. The label from [¹⁴C]acetate and [¹⁴C]malonate was used preferentially for the elongation of endogenous oleate to produce cis-[¹⁴C]11-eicosenoate, cis-13-[¹⁴C]docosenoate, and cis-5,cis-13-[¹⁴C]docosadienoate and for the elongation of endogenous palmitate to produce the remaining C₂₀ and C₂₂ acyl species. The Δ5 desaturation of the preformed acyl chain and chain elongation of oleate and palmitate were demonstrated in vivo by incubation of the appropriate 1-¹⁴C-labeled free fatty acids. Using [1-¹⁴C]acyl-CoA thioesters as substrates, these enzyme activities were also demonstrated in vitro with a cell-free homogenate.     

Inhibition of Topoisomerases by Fatty Acids

The inhibitory effects of various fatty acids on topoisomerases were examined, and their structure-activity relationships and mechanism of action were studied. Saturated fatty acids (C_6:0 to C_22:0) did not inhibit topoisomerase I, but cis-unsaturated fatty acids (C_16:1 to C_22:1) with one double bond showed strong inhibition of the enzyme. The inhibitory potency depended on the carbon chain length and the position of the double bond in the fatty acid molecule. The trans-isomer, methyl ester and hydroxyl derivative of oleic acid had no or little inhibitory effect on topoisomerases I and II. Among the compounds studied petroselinic acid and vaccenic acid (C_18:1) with a cis-double bond were the potent inhibitors. Petroselinic acid was a topoisomerase inhibitor of the cleavable complex-nonforming type and acted directly on the enzyme molecule in a noncompetitive manner without DNA intercalation.     

Effects of Chlorotrifluoroethylene Oligomer Fatty Acids on Recombinant GABA Receptors Expressed in Xenopus Oocytes

GABA-activated Cl⁻ current was expressed in Xenopus oocytes after injecting cRNA that had been transcribed in vitro from complementary DNA (cDNA) coding for a single GABA ρ_i-subunit cloned from human retina. The expressed current was insensitive to 100 μm bicuculline, but was activated by the GABA analogue trans-4-aminocrontonic acid (TACA). Anion-selective permeability of the expressed ρ₁-subunit was determined by isotonically replacing the extracellular Cl⁻ with different anions. The anion permeability was very similar to the native GABA_A receptor/channel following a sequence of SCN⁻ > I⁻ > NO₃ ⁻ > Br⁻≥ Cl⁻. Halogenated fatty acids, such as chlorotrifluoroethylene (CTFE) and perfluorinated oligomer acids inhibited the GABA-induced current in oocytes expressing the human retinal GABA ρ₁-subunit or rat brain GABA_A receptor α₁,β₂,γ₂ subunits. The inhibitory effect of halogenated fatty acids demonstrated a carbon chain length-dependent manner of: C₁₀ > C₈ > C₆ > C₄. Perfluorinated C₈-oligomer acid (PFOA) was less effective at blocking this channel than the C₈-CTFE oligomer acid. Radiolabeled GABA binding assay indicated that CTFE oligomer acids do not interfere at the GABA binding site of the receptor. Furthermore, the C₈-CTFE oligomer fatty acid did not compete with picrotoxin for binding sites within the pore of the channel. These studies demonstrated that the heterologous expression system is useful for studying the molecular interaction between potential neurotoxic agents and neuroreceptors. Our results provide detailed information that should contribute to our understanding of the structure and function of retinal GABA receptors. Received: 12 June 1995/Revised: 21 September 1995     

Etude “in vitro” des acides gras synthétisés dans les microsomes de cerveaux de souris normales et “quaking”

Radiogas chromatographic studies of the products of fatty acid biosynthesis in mice brain microsomes confirm the existence of a «de novo system from acetyl-CoA and malonyl-CoA and of a least two elongating systems for long chain fatty acids, involving malonyl-CoA. The possibility of an intermediary system leading from C₁₈ to C₂₀ fatty acids has been evoked.Comparison between non mutant and quaking mice indicates that all the microsomal fatty acid biosynthetic systems are depressed. The biosynthetic system elongating fatty acids from C₁₈ is the one which is the most modified quantitatively and qualitatively in quaking. Microsomal and soluble «de novo systems are qualitatively intact.     

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.