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A I Leikin

Publications and source records attributed to A I Leikin.

10 recordsLinked to original sources
PubMed1992

In vivo phospholipid modification induces changes in microsomal delta 5-desaturase activity.

The phospholipid composition of rat-liver microsomes was modified by feeding weaning rats a choline-free diet. After 21 days, the phosphatidylcholine content decreased with a concomitant increment of phosphatidylserine and cholesterol. The bulk fluidity of the membrane decreased. Under these conditions, the delta 5-desaturase activity was diminished as well as the arachidonic-acid content of the membrane lipids.

Animals↗
PubMed1989

Fatty acid desaturase activities are modulated by phytosterol incorporation in microsomes.

The effect of phytosterol-rich diets (3% beta-sitosterol + 2% campesterol) on rat liver microsomal fatty acid desaturases, membrane dynamics and lipid composition was investigated. After a 21 day period, phytosterol was incorporated into microsomes and the membrane fluidity decreased. There were no changes in either the phospholipid composition or in the total sterol content. However, the phytosterol/cholesterol ratio increased. In the animals fed phytosterols, the delta 5-, delta 6- and delta 9-fatty acid desaturases were significantly more active than in control animals. The changes in the lipid fatty acid composition were consistent with those of the desaturase activities. Hence, it is suggested that: (1) dietary phytosterol modulates desaturase activities; (2) phytosterols make the membrane more rigid but do not induce changes in the relative phospholipid composition; (3) delta 9-, delta 5- and delta 6-desaturase activities increase when the membrane becomes more rigid without changes in the phospholipid composition.

Animals↗
PubMed1989

Microsomal delta 5 desaturation of eicosa-8,11,14-trienoic acid is activated by a cytosolic fraction.

delta 5 Desaturation of eicosa-8,11,14-trienoic acid to arachidonic acid was studied in rat liver microsomes. It was shown that delta 5 desaturation of fatty acids in vitro requires the participation of a peripheral component of cytosolic origin. Desaturation of 20:3n-6 to 20:4n-6 decreases in washed microsomes as they lose an adsorbed cytosolic fraction (CF), but the enzymatic activity can be recovered as a function of CF concentration in the incubation medium. Albumin does not substitute for CF. delta 5 Desaturation of 20:3n-6 is inhibited by arachidonic acid by a product inhibition effect, but CF prevents retroinhibition of delta 5-desaturase by 20:4n-6. This ability of CF is eliminated by preincubation of CF with 20:4n-6, but not with gamma-18:3n-6, the product of delta 6 desaturation of 18:2n-6, thus indicating that CF impairs the retroinhibitory effect of arachidonic acid on delta 5-desaturase in a specific manner. delta 6 Desaturation of linoleic acid to gamma-18:3n-6 is also activated by CF and retroinhibited by gamma-18:3n-6. CF activity on delta 6 desaturation is retained after preincubation with 20:4n-6, but it is lost after preincubation with gamma-18:3n-6. Activation of delta 6-desaturase by CF is associated with the removal of the reaction product in a specific manner. Chromatography of CF by Sephacryl S-200 separates two major subfractions which show different efficiency in reactivating delta 5- and delta 6-desaturase activities in washed microsomes. Therefore, CF may contain subfractions that can prevent delta 5- and delta 6-desaturase retroinhibition by apparently binding their respective reaction products specifically.

8,11,14-Eicosatrienoic Acid↗
PubMed1988

In vivo cholesterol removal from liver microsomes induces changes in fatty acid desaturase activities.

Rats fed a 1% cholesterol and 0.5% cholate diet for 21 days were transferred to a sterol-free diet after variable periods of time. The effect of cholesterol removal on liver microsomal composition and fatty acid desaturases was studied. Some changes were already observed after 1 day. However, after 21 days of a sterol-free diet, the cholesterol content of liver microsomes decreased as well as that of phosphatidylcholine. So did the cholesterol/phospholipid ratio. Phosphatidylinositol, phosphatidylserine and sphingomyelin slightly increased along with time. The total fatty acid composition was altered by a decrease in monounsaturated acids and an increase in the saturated acids, palmitic and stearic acids. The arachidonic acid content rose. A similar pattern of change was found in the fatty acid composition of the main phospholipids: phosphatidylcholine and phosphatidylethanolamine. delta 9-Desaturase activity steadily decreased along with cholesterol removal, whereas delta 5- and delta 6-desaturase activities were enhanced towards the end of the removal period. The microsomal membrane became more 'fluid', according to the decrease of fluorescence anisotropy of the 1,6-diphenyl-1,3,5-hexatriene incorporated into the membrane.

Animals↗
PubMed1987

Cholesterol-induced microsomal changes modulate desaturase activities.

The effect of 1% dietary cholesterol and 0.5% cholate on the rat liver microsomal composition and fatty acid desaturase activities was studied over various periods of time. The cholesterol content of liver microsomes increased as well as that of phosphatidylcholine. Cholesterol/phosphatidylcholine and phosphatidylcholine/phosphatidylethanolamine ratios were also elevated. Phosphatidylinositol decreased, but it recovered its original values at the end of the experimental period. Phosphatidylserine and sphingomyelin slightly decreased with time. Fatty acid composition changes were expressed by a saturated acid decrease and monounsaturated acid increase. Arachidonic acid content was also reduced. A similar pattern appeared in the main phospholipids: phosphatidylcholine and phosphatidylethanolamine. Delta 9-Desaturase activity was enhanced as early as 48 h after cholesterol administration, whereas delta 5- and delta 6-desaturases were depressed during the same period and this enzymatic behaviour remained after 21 days of diet administration. The microsomal membrane was rigidized, as demonstrated by the increase of the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene.

Animals↗
PubMed1986

Regulation of linoleic acid delta 6-desaturation by a cytosolic lipoprotein-like fraction in isolated rat liver microsomes.

A peripheral component of the delta 6-fatty acid-desaturase system of rat liver microsomes has been isolated from the cytosol by ultracentrifugation at a saline density of 1.26 g/ml. It exhibited lipoprotein characteristics with an approximate protein/lipid ratio of 1.22 and free fatty acids and phosphatidylcholine as its main lipid components. Linoleic acid desaturation activity diminished in washed microsomes, since they lost the adsorbed cytosolic fraction. Addition of the factor reactivated the reaction and the recovery was dependent on the concentration of the factor in the medium. Linoleic acid and linoleyl-CoA were bound by the cytosolic fraction. However, the transport of substrate to the desaturase was not apparently a main function of the cytosolic fraction, since transport occurred equally in the absence of the factor. Moreover, the solubilization of linoleyl-CoA was not enhanced and the free monomeric concentration was not altered by the presence of the cytosolic fraction. In addition, the factor did not divert delta 6-desaturase substrate to or from other metabolic pathways such as esterification to phospholipids. gamma-Linolenic acid produced by delta 6-desaturation of linoleic acid in the microsomes inhibited the desaturase, but it was removed by the factor from the membrane towards the cytosol, preventing the inhibition. The anti-inhibitory effect of the cytosolic factor was blockaded by addition of columbinic acid or gamma-linolenic acid to the factor. Moreover, the inhibitory effect of arachidonic acid was not prevented by addition of the cytosolic fraction. These results suggest that the cytosolic fraction studied would optimize the delta 6-desaturation of linoleic acid in vitro in rat liver microsomes by removal of the product, gamma-linolenic acid, as it is formed.

Animals↗
PubMed1980

Effect of ethanol administration on fatty acid desaturation.

The effect of ethanol on the fatty acid desaturation by rat liver has been studied using liquid diets of different composition. Acute ethanol administration increased triacylglycerols of total liver lipids, but did not modify significantly the lipidic composition of microsomes. The delta 6 and delta 5 desaturases were inhibited by ethanol whereas the delta 9 desaturase and fatty acid synthetase were apparently modified only by diet composition. NADH-cytochrome (cyt.) c reductase was partially inhibited, whereas NADH-cyt. b5 reductase remained practically unaltered and NADPH-cyt. c reductase activity was enhanced. Decreased electrons supplied by the microsomal cyt. b5 electron transport chain would not be the reason for the inhibition of delta 6 and delta 5 desaturases by ethanol.

Animals↗
PubMed1980

Effect of temperature on the structure of rat liver microsomes studied by electron spin resonance, fluorescence and activity of enzymes involved in fatty acid biosynthesis.

The structural properties of rat liver microsomes were studied by physical and kinetic methods. The microsomes and the lipids extracted from the microsomes were labeled with 16-doxyl-stearic acid- and N-phenyl-1-naphthylamine. The electron spin resonance spectra and the fluorescence intensities were respectively determined at different temperatures from approximately 10 to 40 C. Both methods suggested the absence of a transition temperature indicative of a phase change in the bulk of the lipids of the microsomes in the temperature range studied. The fluidity of the lipid bilayer increased smoothly with the temperature. The Arrhenius plots of the NADH-ferricyanide reductase, NADH-cyt.c reductase, delta 9 desaturase, delta 6 desaturase and palmitic elongation to stearic acid also indicated the absence of a detectable change of phase from crystalline to liquid crystalline in the boundary lipids of these enzymes from 10 C to 40 C. The transference of electrons from the NADH-cyt.b5 reductase to the cyt.b5 is the rate limiting step in the first parts of the electron transport chain. However, the delta 9 desaturase is the rate limiting step of all the series of reactions involved in the delta 9 fatty acid desaturation. Similar conclusions may be extended to the delta 6 desaturation of fatty acids. The physical state of the lipids surrounding the desaturating system would be different from boundary lipids of the cyt.P450 system.

Animals↗
PubMed1979

Lipid binding properties of a factor necessary for linoleic acid desaturation.

Suspension and centrifugation of crude microsomes of rat liver in low ionic strength solution separated a soluble protein fraction that is necessary for the full activity of the linoleic acid desaturase. The fraction partially purified through Sephadex G-150 still retains lipids which are mainly constituted by phosphatidycholine. Linoleic acid predominates in the fatty acid composition. By NaCl gradient centrifugation and electrophoresis in gelatinized cellulose acetate, the factor behaves like a lipoprotein. The factor binds linoleic acid and linoleyl-CoA that are desaturated to gamma-linolenic acid when incubated with washed microsomes. Albumin does not replace the factor.

Animals↗