• Proceedings of the KSAR Conference
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• 2000.10a
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• pp.3-4
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• 2000

The synthesis of acyl-CoA catalyzed by acyl-CoA synthetase (ACS, EC 6.2.1.3) from fatty acid, ATP, and CoA is a crucial reaction in mammalian fatty acid metabolism. In arachidonate metabolism, acyl-CoA synthetase(ACS) plays a key role in the esterification of free arachidonate into membrane phospholipids. Following its release by the action of calcium dependent phospholipase, free arachidonate is believed to be rapidly converted to arachidonoyl-CoA and reesterified into phospholipids in order to prevent excessive synthesis of eicosanoids. In previous studies, we have characterized five ACSs (designated as ACS1-5) with different tissue distribution. ACS1, ACS2, and ACS5 are similar in structure and fatty acid preference, and completely different from ACS3 and ACS4. The latter are arachidonate-preferring enzymes closely related in structure but expressed in different tissues: ACS3 mRNA is highly expressed in the brain and the mRNA for ACS4 is expressed in steroidogenic tissues including adrenal gland, ovary, and testis. To learn more about the potential function of ACS4 in arachidonate metabolism, we have produced knock-out mice for ACS4 gene. ACS4+/- females become pregnant less frequently and produce small litters with extremely low transmission of the disrupted alleles. Striking morphological changes including extremely enlarged uterine filled with numerous proliferative cysts of various size were detected in ACS4+/- females. Furthermore, marked accumulation of prostaglandins were seen in the uterus of heterozygous females. These results indicate that ACS4 is critical for the uterine arachidonate metabolism and heterozygous disruption of its gene lead to impaired pregnancy.

• Nutritional Sciences
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• v.6 no.1
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• pp.20-24
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• 2003

The effect of a-tocopherol on the formation and accumulation of phospholipid hydroperoxides, especially of phosphatidylcholine hydroperoxides, in the tissues of 2, 2 -azobis Hydrochloride (AAPH) - dosed rats was investigated. In a-tocopherol supplemented rats, the activities of glutathione peroxidase, catalase and superoxide dismutase were significantly inhibited, compared with the AAPH group. AAPH treatment led to oxidation of phospholipids in the liver, lungs, brain, plasma and red blood cells (RBC), resulting in a notable increase in phosphatidylcholine hydroperoxide (PCOOH). All tissues of the rats given an $\alpha$-tocopherol supplement showed an attenuation of the stimulating effect of AAPH, leading to low levels of formation of PCOOH. Also, the rats injected with AAPH and a-tocopherol showed relatively normal-appearing hepatocytes, except for a little loss of the granules. With regards to the morphological appearance of the liver, it was observed that oral intakes of a -tocopherol resulted in an antioxidant defense against attacks of peroxyl radicals. Thus, we suggest that a-tocopherol is potentially helpful in protecting membrane phospholipids against oxidative damage in vivo.

• The Korean Journal of Pain
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• v.6 no.1
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• pp.67-73
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• 1993

소의 신선한 대뇌피질로부터 synaptosomal plasma membrane vesicles(SPMV)를 분리한 후 이 SPMV로부터 추출한 모든 인지질들로서 제제한 인공세포막(SPMVPL)에서의 n-alkanols 침투 정도를 형광 probe를 이용한 형광 소광법을 통하여 검색하였다. n-alkanols는 SPMVPL 외부 단층(outer monolayer)의 표면에 주로 분포하되 그 탄소수에 비례하여 소수성 부위에 분포되는 양이 증가되는 경향을 나타내었다. methanol, ethanol, 1-propano, 1-butanol, 1-pentanol, 1-hexanol, 1-heptanol, 1-octanol, 1-nonanol 및 1-decanol은 SPMVPL 외부 단층의 표면(친수성 부위)에 분포되는 것이 소수성 부위에 분포되는 것에 비하여 각각 432.4, 208.9. 125.6, 88.2, 19.3, 7.9, 2.6, 1.0, 0.42, 1.36배가 되었다. 1-decanol은 $C_{10}$인데도 불구하고 $C_8$인 1-octanol에 비하여 적은 양이 소수성 부위에 침투 분포된다는 것이 확인되었다. n-alkanols의 침투에 대하여 저자등이 이미 보고한 바 있는 SPMV 및 SPMVTL(cholesterol+phospholipids)의 경우보다도 본 연구에서의 SPMVPL의 경우가 현저하게 많은 양이 소수성 부위로 침투 분포된다는 것도 확인되었다.

• BMB Reports
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• v.38 no.3
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• pp.360-365
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• 2005

Membrane inositol glycerophospholipid (IGP) is metabolized to phosphatidylinositol-4-phosphate (PIP), phosphatidylinositol-4, 5-bisphosphate ($PIP_2$), and inositol triphosphate ($IP_3$) in signaling transduction. This study was carried out to determine the subclasses of IGP involved in signaling pathway. The acyl chain moieties of the phospholipids are easily modulated by dietary fatty acids. We analyzed acyl chain composition of IGP 3-subclasses, PIP and $PIP_2$ from rat brain after feeding sunflower seed oil enriched with linoleic acid or fish oil high in eicosapentaenoic acid and docosahexaenoic acid. Long chain polyunsaturated fatty acids (LCPUFA) as eicosapentaenoic acid and docosahexaenoic acid were not incorporated into ether-linked IGP (alkenylacylglycerophosphoinositol and alkylacyl-glycerophosphoinositol), PIP and $PIP_2$, while diacyl-glycerophosphoinositol (GPI) contained high LCPUFA. These results suggest that PIP might be phosphorylated from only the ether-linked IGP (alkenylacyl- and alkylacyl species) but not from diacyl subclass for signals to intracellular responses in the plasma membrane of rat brain.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.2
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• pp.151-156
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• 2022

Liposomes are bilayered particles that are surrounded by an aqueous solvent with amphiphilic substances such as phospholipids. Liposomes have the potential to overcome the limitations of physiochemical properties of existing drugs, and are therefore widely used in research for the treatment of many diseases, especially cancer. Currently, there are many liposome manufacturing methods that use various lipids and amphiphiles. Among them, the thin film-hydration method is a traditional and very simple method to prepare liposomes by hydrating a dry lipid film in an aqueous solvent, which has been widely used in the laboratory until recently. Recently, approaches to new nuclear imaging agents and radiotherapy by loading radioactive isotopes inside liposomes have been actively studied. In this review, we would like to discuss considerations for preparing liposomes using the thin film-hydration method.

• Journal of Nutrition and Health
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• v.29 no.8
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• pp.849-860
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• 1996

The supply of different fatty acids during the development period has significant effects. This study examined the effects of dietary $\omega$3 and $\omega$6 fatty acid compositions on phospholipids (PLs) of RBC and rat brain subcellular fractions (synaptosome, microsome, mitochondria), and on learning ability of the 2nd generation rat. Rats were fed experimental diets 3-4 wks prior to the conception. Early in the lactation period, the feeding mothers were exchanged. Diets consisted of 10% fat(by weight), which was either safflower oil('S') poor in $\omega$3 fatty acids or computer-searched mixed oil('M') with P/M/S ratio, 1/1.4/1 and $\omega$6/$\omega$3 ratio, 6.1/1. The 'S' and 'M' rats were subdivided further into SS, SM, MS & MM rats according to their lactation stauts. At 3 (weaning) & 9 wks of age, the percentage of total $\omega$3 fatty acids to their lactation status. At 3 (weaning) & 9 wks of age, the percentage of total $\omega$3 fatty acids and the ratios of $\omega$3/$\omega$6 fatty acids in PLs of RBC and brain subcellular fractions in SM and MM groups fed milk from the mixed oil-fed mothers for 2 wks tended to be higher than those in SS and MS groups respectively. In contrast, the concentrations of $\omega$6 fatty acids, especially 22:5$\omega$6 in all fractions, were significantly lower in the SM & MM groups compared to those of the SS & MS groups respectively. In contrast, the concentration of $\omega$6 fatty acids, especially 22:5$\omega$6 in all fractions, were significantly lower in the SM & MM groups compared to those of the SS & MS groups, The values for the DHA$\omega$3/22:5$\omega$6 ratios after the lactation period were markedly higher in the groups (SM & MM) which were reared by mixed oil(MO) fed mothers. In carring out Y-water maze at 9th wk of age, the SM(4.2$\pm$0.5) & MM (5.3$\pm$0.5) groups made significantly less errors compared to the SS(6.2$\pm$0.6, p<0.05 compared with SM) & MM (7.2$\pm$0.5, p<0.05 compared with MM) groups which were lactated by the safflower oilfed mothers. Therefore, by feeding a balanced fatty acid diet from the lactation period up to 9 wks of age as compared with the groups fed $\omega$3 fatty acid-deficient diet regardless of mother's diet given before parturition. The levels of DHA(synaptosome) and 22:5$\omega$3 (mitochondria) were positively correlated not only with these values in RBC but also with visual discriminating ability. The levels of DHA and 22:5$\omega$3 in RBC can, therfore, reflect visual discriminatng ability in the rat.

• Journal of Applied Biological Chemistry
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• v.42 no.2
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• pp.75-80
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• 1999

The effects of dietary n-3 fatty acids, ${\alpha}$-linolenic acid (18:3), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6), on brain phospholipid content and fatty acid composition were compared in rats fed with a diet containing constant ratios of saturated fatty acid/monounsaturated fatty acid/polyunsaturated fatty acid (PUFA) and n-3/n-6. The dietary fat in each diet was added at the level of 10%. In each diet, n-3 PUFA comprised two-thirds of the PUFA and the remaining one-third was linoleic acid (18:2). Dietary fat containing linoleic acid as the sole source of PUFA was also given to the control group. The content of brain phospholipid in the three n-3 PUFA groups was significantly lower than that of the linoleic acid group. This reduction was greater in the EPA and DHA groups than in the ${\alpha}$-linolenic acid group. The decrease in phospholipid content in rats fed n-3 fatty acid-rich diets was largely due to the decrease in the phosphatidylethanolamine fraction. Each dietary n-3 PUFA was found to affect the fatty acid composition of brain phospholipids; the most pronounced alteration was observed in phosphatidylethanolamine fraction. Furthermore, the proportion of DHA in the phosphatidylethanolamine fraction tended to be higher in the DHA group than in other PUFA groups. In conclusion, dietary ${\alpha}$-linolenic acid, EPA and DHA can influence the phospholipid content, phospholipid subclass, and fatty acid composition in rat brain.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.106-106
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• 2003

Choline serves critical roles in the CNS both as a precursor of neurotransmitter and as an essential component of membrane phospholipids. The long-term maintenance of brain choline concentration is dependent on choline transport across the blood-brain barrier (BBB), And, we examined to elucidate the characteristics of transport of choline across the BBB using conditionally immortalized rat brain capillary endothelial cell line (TR-BBB) in vitro. The ［$^3$H］choline in TR - BBB was increased by time dependently, but independent on Na$\^$＋/, and the transport process is saturable with Michaelis-Menten constrant, Km of about 26 ${\mu}$M. The uptake of ［$^3$H］choline is susceptible for inhibition by various organic cationic compounds including hemicholinium-3, tetraethylammonium chloride (TEA) and $\ell$-carnitine. Also, we investigated the relationship of transport of choline and cationic drugs. The uptake of ［$^3$H］choline is inhibited by antioxidant, a-phenyl-n-tert-butyl nitrone (PBN) with IC$\sub$50/ of 1.2 mM. and by Alzheimer's disease therapeutics, such as acetyl $\ell$-carnitine, tacrine and donepezil. Also, choline uptake presented competitive inhibition with PBN, donepezil and acetyl $\ell$-carnitine in Lineweaver-Burk plot. In conclusion, TR-BBB cells express a saturable transport system for uptake of choline, and several cationic drugs may be transported into the brain by BBB choline transporter.

• Applied Biological Chemistry
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• v.38 no.4
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• pp.320-324
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• 1995

Solubilization of microsomal ${\Delta}^{5}-3{\beta}$-hydroxy steroid acyl transfearse(${\Delta}^{5}-3{\beta}$-OH-SAT) of rat brain and its reconstitution into liposomes were investigated. Among the detergents utilized for the solubilization, deoxycholic acid was superior to Tween 80 or Triton X-100 for the reconstituted activity of ${\Delta}^{5}-3{\beta}$-OH-SAT. The enzyme activity was shown to be affected by the nature of phospholipids used for the preparation of the liposome. Phosphatidylcholines from egg yolk and soybean showed the highest activity of ${\Delta}^{5}-3{\beta}$-OH-SAT and phosphatidylethanolamine came next. However phosphatidylserine and phosphatidic acid showed a lower activity than those obtained before the reconstitution. This study suggests that the presence of quaternary ammonium salt or amine group in the phospholipids stimulates the activity of ${\Delta}^{5}-3{\beta}$-OH-SAT. However the presence of a carboxylic group or the absence of the amine group may have an inhibitory effect on the ${\Delta}^{5}-3{\beta}$-OH SAT.

• Journal of Nutrition and Health
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• v.18 no.3
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• pp.242-248
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• 1985

Weanling female Sprague Dawley rats were fed diets containing 22mg pyridoxine HCI/kg diet(control diet) and 1.2mg pyridoxine HCI/kg diet(deficient diet). One deficient group and one control group were fed their diets throughout the period of growth, gestation and lactation. After the pups were born and weaned, the deficient group was divided into two groups. Therefore, one(DC) switched to control diet and the other continued the same deficient diet until 10 week-old. Analysis of chemical composition of fatty acid in the total brain lipid was conducted in the pups of 5, 10, 15, 21, 35, 50 days of age. Arachidonic acid content was significantly decreased in the deficient group at 5 days compared to the control, but at almost all ages, there were no significant differences in fatty acid contens among all the groups. The fatty acid compositions of the brain phospholipids were determined on pups at 1, 14, 21, 35, 70 days of age. The content of $C_{20}\;_{4}$ in the brain phosphatidylcholine birth and contents of $C_{22}\;_{4}$ and $C_{22}\;_{5}$ at birtd, and $C_{22}\;_{5}$ and $C_{22}\;_{6}$ at 14 days in the phosphatidylethanolamine were depressed in the deficient group. These changes were not consistent with ages. Therefore, it may reflect that the major part of the changes occuring in the pyridoxine depleted rats depends, not so much on the pyridoxine depletion itself, as on the age or development of the rats.