n-3 and n-6 polyunsaturated fatty acids have different effects on acyl-CoA:cholesterol acyltransferase in J774 macrophages.

The effects of incubating J774 mouse macrophages with different fatty acids on cholesterol esterification were investigated. In cells incubated with n-3 polyunsaturated fatty acids, the rate of cholesterol esterification was significantly reduced compared with cells incubated with n-6 polyunsaturated fatty acids or with oleic acid. This change in cholesterol esterification appears to be the result of reductions in the activity of acyl-CoA:cholesterol acyltransferase (ACAT) in the endoplasmic reticulum of the macrophages incubated with the n-3 polyunsaturated fatty acids. No differences in microsomal cholesterol were observed among cells incubated with different fatty acids. However, cellular cholesterol levels were lower in cells incubated with n-3 polyunsaturated fatty acids. In microsomes from cells incubated with n-3 polyunsaturated fatty acids, both the Km and the Vmax of ACAT were lower than in microsomes from cells incubated with n-6 fatty acids or oleic acid. These findings may explain some of the reduction in atherosclerotic lesions that are observed with dietary fish oils that contain high levels of n-3 polyunsaturated fatty acids.     

Uptake and metabolic conversion of saturated and unsaturated fatty acids in Hep2 human larynx tumor cells

Research on fatty acid metabolism in cultured human larynx tumor cells Hep2 was carried out.The cells were incubated with either a saturated (palmitic) or a polyunsaturated (linoleic, alpha-linolenic and eicosatrienoic (n-6)) radioactive fatty acid (0.66 pM, 24 h). The best incorporation capacity was observed in the linoleic acid followed by alpha-linolenic, palmitic and eicosatrienoic acids. All fatty acids tested were anabolized to higher derivatives within their own family. Palmitic acid was primarily monodesaturated rather than elongated, proving to have a very active A9 desaturase activity.With respect to polyunsaturated acid metabolism, the conversion of alpha-linolenic acid to higher homologs, although better than linoleic acid, occurred far less efficiently than that observed in other non-highly undifferentiated human tumor cells. This impairment in higher polyunsaturated fatty acid biosynthesis, reflected in the low levels of arachidonic acid in the fatty acid composition, would not reside in the A5 desaturation step since Hep2 cells can readily convert eicosatrienoic acid into arachidonic acid. Considering the potential regulatory role of specific polyunsaturated fatty acids in the cell proliferative control, the knowledge of the metabolism of fatty acids in this human tumor cell would be important for designing future experiments in order to clarify the mechanism involved in balance, proliferation and cell death.     

Nutritional intervention with omega-3 fatty acids enhances tumor response to anti-neoplastic agents

Nutritional intervention with specific fatty acids depresses tumor growth and enhances tumor responsiveness to chemotherapy. Supplementation of tumors with long chained omega-3 polyunsaturated fatty acids results in enrichment of tumor phospholipid fractions with omega-3 fatty acids resulting in an altered membrane composition and function. Tumors enriched with long chained omega-3 polyunsaturated fatty acids possess membranes with increased fluidity, an elevated unsaturation index, enhanced transport capabilities that results in accumulation of selective anti-cancer agents, increased activity of selected drug activating enzymes, and alteration of signaling pathways important for cancer progression. These nutritionally induced changes in tumor fatty acid composition result in increased sensitivity to chemotherapy, especially in tumor lines that are resistant to chemotherapy and cause specific enhancement of cytotoxicity to tumor cells and protection of normal cells. Pre-disposing tumors to increased chemo-sensitivity through nutritional intervention with specific fatty acids has the potential to improve patient response to chemotherapy with fewer untoward side effects if these pre-clinical findings carry over into a clinical setting.     

Fatty acid metabolism of isolated mammalian cells

It is now clear that a wide variety of differentiated cells in culture exhibit essentially the full spectrum of mammalian fatty acid metabolism. These cells readily incorporate free fatty acids into membrane phosphoglycerides, modify exogenous fatty acids by desaturation and elongation, and store excess fatty acyl groups, primarily as triacylglycerols. Similarly, many different types of cells synthesize cyclooxygenase and lipoxygenase derivatives of long chain polyunsaturated fatty acids. Furthermore, although the fatty acid composition of cellular phospholipids can be modified by medium supplementation, cells in culture exhibit definite fatty acyl specificities for the various steps of fatty acid activation, transesterification and release. As the extensive repertoire of fatty acid metabolism in mammalian cells has been elucidated, and as the ability to grow differentiated cells in culture has increased, new questions have arisen. There is still much to be learned about the enzymes involved in synthesizing and maintaining the unique fatty acid composition of the different cellular phospholipids and the processes which regulate the desaturation, elongation and retroconversion of polyunsaturated fatty acids. Other areas of great current interest are the mechanisms by which certain long chain polyunsaturated fatty acids are made available for conversion to oxygenated, biologically-active derivatives, the metabolic interactions between different polyunsaturated fatty acids, particularly n-3 and n-6 fatty acids, the cellular roles of the C22 polyunsaturated fatty acids, and the functions of particular molecular species of phospholipids in membrane-mediated events. Further research in these areas will contribute to unravelling the role of fatty acids and fatty acid derivatives in the physiological processes of mammalian cells.     

Uptake and incorporation of saturated and unsaturated fatty acids into macrophage lipids and their effect upon macrophage adhesion and phagocytosis.

Murine thioglycollate-elicited peritoneal macrophages were cultured in the presence of a variety of fatty acids added as complexes with bovine serum albumin. All fatty acids tested were taken up readily by the cells and both neutral and phospholipid fractions were enriched with the fatty acid provided in the medium. This generated a range of cells enriched in saturated, monounsaturated or polyunsaturated fatty acids, including n-3 acids of fish oil origin. Saturated fatty acid enrichment enhanced macrophage adhesion to both tissue culture plastic and bacterial plastic compared with enrichment with polyunsaturated fatty acids. Macrophages enriched with the saturated fatty acids myristate or palmitate showed decreases of 28% and 21% respectively in their ability to phagocytose unopsonized zymosan particles. Those enriched with polyunsaturated fatty acids showed 25-55% enhancement of phagocytic capacity. The greatest rate of uptake was with arachidonate-enriched cells. Phagocytic rate was highly correlated with the saturated/unsaturated fatty acid ratio, percentage of polyunsaturated fatty acid and index of unsaturation, except for macrophages enriched with fish-oil-derived fatty acids; they showed lower phagocytic activity than expected on the basis of their degree of unsaturation. These results suggest that membrane fluidity is important in determining macrophage adhesion and phagocytic activity. However, in the case of phagocytosis, this effect may be partially overcome if the cells are enriched with fish-oil-derived fatty acids. Thus it may be possible to modulate the activity of cells of the immune system, and so an immune response, by dietary lipid manipulation.     

Interactions between P-limitation and different C conditions on the fatty acid composition of an extremophile microalga

The extremophilic microalga Chlamydomonas acidophila inhabits very acidic waters (pH 2-3.5), where its growth is often limited by phosphorus (P) or colimited by P and inorganic carbon (CO(2)). Because this alga is a major food source for predators in acidic habitats, we studied its fatty acid content, which reflects their quality as food, grown under a combination of P-limited and different carbon conditions (either mixotrophically with light + glucose or at high or low CO(2), both without glucose). The fatty acid composition largely depended on the cellular P content: stringent P-limited cells had a higher total fatty acid concentration and had a lower percentage of polyunsaturated fatty acids. An additional limitation for CO(2) inhibited this decrease, especially reflected in enhanced concentrations of 18:3(9,12,15) and 16:4(3,7,10,13), resulting in cells relatively rich in polyunsaturated fatty acids under colimiting growth conditions. The percentage of polyunsaturated to total fatty acid content was positively related with maximum photosynthesis under all conditions applied. The two factors, P and CO(2), thus interact in their effect on the fatty acid composition in C. acidophila, and colimited cells P-limited algae can be considered a superior food source for herbivores because of the high total fatty acid content and relative richness in polyunsaturated fatty acids.     

Multidimensional gas chromatography-mass spectrometry for tracer studies of fatty acid metabolism via stable isotopes in cultured human trophoblast cells

The determination of placental fatty acid metabolism using stable isotope-labeled tracers was investigated in the human placental choriocarcinoma (JAR) cell line. Stable isotope incorporation was measured by MDGC-MS. The cultured trophoblast cells incorporated and metabolized the essential fatty acids to long-chain polyunsaturated fatty acids. The described method enables the detection of a low Delta(6)-desaturase activity in this human placental cell line. The developed MDGC-MS method allows the assessment of long-chain polyunsaturated fatty acid biosynthesis in cultured cells with high sensitivity and selectivity. In this respect, tracer studies with MDGC-MS will be a powerful tool to clarify the significance of placental fatty acid metabolism.     

Effects of different types of polyunsaturated fatty acids on cholesterol esterification in human fibroblasts.

We have enriched human fibroblasts with oleic acid, with linoleic acid and with eicosapentaenoic acid. The accumulation of cholesteryl esters in the cells and the rate of esterification of cholesterol by microsomal acyl-CoA:cholesterol acyltransferase (ACAT) were measured in these cells. Cholesteryl ester levels were lower in cells enriched with eicosapentaenoic acid compared with cells enriched with oleate or linoleate. We also observed significantly lower ACAT activities in the microsomes from fibroblasts enriched with the n-3 polyunsaturated fatty acids relative to cells enriched with oleic acid or linoleic acid. We suggest that the presence of n-3 polyunsaturated fatty acids might suppress cholesteryl ester accumulation and inhibit atherogenesis.     

Metabolism of n -9, n -6 and n -3 fatty acids in hepatoma Morris 7777 cells. Preferential accumulation of linoleic acid in cardiolipin

The objective of this study was to investigate, using a pulse-chase technique, the different incorporation of (1-(14)C) n -9, n -6 and n 3 fatty acids into hepatoma lipids and their secretion to the culture medium. Docosahexaenoic acid (DHA) accumulated preferentially into the triacylglycerol while arachidonic acid (AA) did into the phospholipid fraction. DHA was poorly secreted to the culture medium whereas AA was secreted to a large extent. The fatty acids were initially esterified mainly into phosphatidylcholine and phosphatidylethanolamine. During the 24 h chase, a general shift from phosphatidylcholine to phosphatidylethanolamine was observed. Linoleic acid was esterified in cardiolipin to a much greater extent than any other fatty acid and it was not converted to more polyunsaturated fatty acids.The supplementation of the culture medium with polyunsaturated fatty acids had no inhibitory effect on the growth of the hepatoma cells, in marked contrast to observations made in other tumoral cells. The reasons for the resistance of the hepatoma cells to polyunsaturated fatty acid toxicity, including the possible antioxidant effect of linoleic acid accumulation in cardiolipin, are also discussed.     

Effect of long-chain fatty acids in the culture medium on fatty acid composition of WEHI-3 and J774A.1 cells

As a first step in determining the mechanism of action of specific fatty acids on immunological function of macrophages, a comparative study of the effect of long-chain polyunsaturated fatty acids (PUFA) in the medium was conducted in two macrophage cell lines, J774A.1 and WEHI-3. The baseline fatty-acid profiles of the two cell lines differed in the % distribution of saturated (SFA) and unsaturated fatty acids (UFA). J774A.1 cells had a higher % of SFA (primarily palmitic acid) than WEHI-3 cells. Conversely, WEHI-3 cells had a higher % of UFA (primarily oleic acid) than J774A.1 cells. Neither cell line had detectable amounts of alpha-linolenic acid (ALA) or eicosapentaenoic acid (EPA). The most abundant polyunsaturated fatty acid in both cells lines was arachidonic acid (AA). The efficiency of transport of fatty acids from the medium to the macrophages by two delivery vehicles (BSA complexes and ethanolic suspensions) was compared. Overall, fatty acids were transported satisfactorily by both delivery systems. Alpha-linolenic acid and doscosahexenoic acid (DHA) were transported more efficiently by the ethanolic suspension system. Linoleic acid (LA) was taken up more completely than ALA, and DHA was taken up more completely than EPA by both cell cultures and delivery systems. A dose-response effect was demonstrated for LA, ALA, EPA and DHA in both J774A.1 and WEHI-3 cells. Addition of polyunsaturated fatty acids (PUFA) to the cell cultures modified the total lipid fatty acid composition of the cells. The presence of ALA in the culture medium resulted in a significant decrease in AA in both cell lines. The omega-3/omega-6 fatty acid ratio (omega-3/omega-6), polyunsaturated/saturated fatty acid ratio (P/S), and unsaturation index (UI) increased directly with the amount of PUFA and omega-3 fatty acid provided in the medium. The results indicate that the macrophage cell lines have similar, but not identical, fatty acid profiles that may be the result of differences in fatty acid metabolism. These distinctions could in turn produce differences in immunological function. The ethanol fatty-acid delivery system, when compared with the fatty acid-BSA complex system, is preferable for measurement of dose-response effects, because the cellular fatty acid content increased in proportion to the amount of fatty acid provided in the medium. Similar dose-response results were observed in a previous in vivo study using flaxseed, rich in ALA, as a source of PUFA.     

Docosahexaenoic acid stabilizes soluble amyloid-beta protofibrils and sustains amyloid-beta-induced neurotoxicity in vitro

Enrichment of diet and culture media with the polyunsaturated fatty acid docosahexaenoic acid has been found to reduce the amyloid burden in mice and lower amyloid-beta (Abeta) levels in both mice and cultured cells. However, the direct interaction of polyunsaturated fatty acids, such as docosahexaenoic acid, with Abeta, and their effect on Abeta aggregation has not been explored in detail. Therefore, we have investigated the effect of docosahexaenoic acid, arachidonic acid and the saturated fatty acid arachidic acid on monomer oligomerization into protofibrils and protofibril fibrillization into fibrils in vitro, using size exclusion chromatography. The polyunsaturated fatty acids docosahexaenoic acid and arachidonic acid at micellar concentrations stabilized soluble Abeta42 wild-type protofibrils, thereby hindering their conversion to insoluble fibrils. As a consequence, docosahexaenoic acid sustained amyloid-beta-induced toxicity in PC12 cells over time, whereas Abeta without docosahexaenoic acid stabilization resulted in reduced toxicity, as Abeta formed fibrils. Arachidic acid had no effect on Abeta aggregation, and neither of the fatty acids had any protofibril-stabilizing effect on Abeta42 harboring the Arctic mutation (AbetaE22G). Consequently, AbetaArctic-induced toxicity could not be sustained using docosahexaenoic acid. These results provide new insights into the toxicity of different Abeta aggregates and how endogenous lipids can affect Abeta aggregation.     

Lipid composition ofAcetabularia mediterranea (Lamour.) Variations during cap morphogenesis

Summary YoungAcetabularia mediterranea cells without cap have a fatty acid composition different from other green algae currently used for biological research. They contain important quantities of palmitic and oleic acid, but are very poor in polyunsaturated fatty acids such as linoleic and linolenic acid. (These polyunsaturated fatty acids are predominant in higher plants and many green algae.)     

Fatty acid metabolism in Paramecium. Oleic acid metabolism and inhibition of polyunsaturated fatty acid synthesis by triparanol

Paramecium requires oleic acid for growth and can grow in media containing no other fatty acids. In the present study, we have shown that this ciliate utilized oleate mainly as a carbon and energy source, even though this fatty acid was the only substrate available for synthesis of polyunsaturated fatty acids. Culture growth was inhibited by the addition of the drug triparanol. Triparanol decreased the formation of polyunsaturated fatty acids from oleate by preventing desaturation to form the dienoic acid, linoleate. Triparanol inhibition resulted in an altered phospholipid fatty acyl composition, an increased fragility and an altered behavioral response of the cells to a depolarizing stimulation solution. Therefore, although most of the dietary oleate was not used by the cells for polyunsaturated fatty acid synthesis, the desaturation of oleic acid was critical for normal culture growth, cell integrity and swimming behavior, all of which are expected to be dependent on normal membrane lipid composition.     

Electron-spin resonance studies of lipid-modified microsomes from Friend erythroleukemia cells

The fatty acid composition of cultured Friend erythroleukemia cells was modified by supplementation of the medium with oleic or linoleic acid. There was a 30% reduction in saturated and a 35% reduction in polyunsaturated fatty acids in microsomal phospholipids when the cells were grown in media supplemented with oleic acid, and a 3-fold increase in polyunsaturated fatty acids when the cells were grown in linoleic acid-supplemented media. Electron-spin resonance studies with the 5-nitroxystearate probe demonstrated that there was no appreciable change in microsomal lipid mobility as measured by the order parameters. In contrast, changes in lipid mobility were detected with the spin-label probe when microsomes were first isolated from Friend erythroleukemia cells and subsequently modified by incubation with liposomes composed of either dioleoyl- or dilinoleoylphosphatidylcholine plus bovine liver phospholipid-exchange protein. The fatty acid compositional changes produced in these microsomes were similar to those obtained when the intact cells were grown in media containing supplemental fatty acids. These findings indicate that the lipid mobility of Friend cell microsomes can be altered by phospholipid replacements in vitro, but that this does not occur when similar microsomal fatty acid modifications are produced during culture of the intact cell.     

Characterization of highly purified ornithine decarboxylase from rat heart

The fatty acid composition of cultured Friend erythroleukemia cells was modified by supplementation of the medium with oleic or linoleic acid. There was a 30% reduction in saturated and a 35% reduction in polyunsaturated fatty acids in microsomal phospholipids when the cells were grown in media supplemented with oleic acid, and a 3-fold increase in polyunsaturated fatty acids when the cells were grown in linoleic acid-supplemented media. Electron-spin resonance studies with the 5- nitroxystearate probe demonstrated that there was no appreciable change in microsomal lipid mobility as measured by the order parameters. In contrast, changes in lipid mobility were detected with the spin-label probe when microsomes were first isolated from Friend erythroleukemia cells and subsequently modified by incubation with liposomes composed of either dioleoyl- or dilinoleoylphosphatidylcholine plus bovine liver phospholipid-exchange protein. The fatty acid compositional changes produced in these microsomes were similar to those obtained when the intact cells were grown in media containing supplemental fatty acids. These findings indicate that the lipid mobility of Friend cell microsomes can be altered by phospholipid replacements in vitro, but that this does not occur when similar microsomal fatty acid modifications are produced during culture of the intact cell.     

Choline Uptake in Cultured Human Y79 Retinoblastoma Cells: Effect of Polyunsaturated Fatty Acid Compositional Modifications

Abstract: Choline uptake in Y79 human retinoblastoma cells occurs through two kinetically distinguishable processes. The high-affinity system shows little sodium or energy dependence, and it does not appear to be linked to acetyl CoA: choline O -acetyltransferase. When the cells are grown in a culture medium containing 10% fetal bovine serum, the high-affinity system has a K' _m= 2.16 ± 0.13 μ m and V' _max= 27.0 ± 2.9 pmol min⁻¹ mg⁻¹, whereas the low-affinity system has K' _m= 20.4 ± 1.3 μ m and V' _max= 402 ± 49 pmol min⁻¹ mg⁻¹. Under these conditions, the polyunsaturated fatty acid content of the cell membranes is relatively low. When the polyunsaturated fatty acid content of the microsomal membrane fraction was increased by supplementing the culture medium with linolenic or docosahexaenoic acids (n-3 polyunsaturated fatty acids) or arachidonic acid (n-6 polyunsaturated fatty acid), the K' ^m of the high-affinity choline transport system was reduced by 40–60%. The V' _max also was reduced by 20–40%. Supplementation with oleic acid, the most prevalent monounsaturated fatty acid, did not affect either kinetic parameter. The results suggest that one functional effect of the high unsaturated fatty acid content of neural cell membranes is to facilitate the capacity of the high-affinity choline uptake system to transport low concentrations of choline. This effect appears to be specific for polyunsaturated fatty acids but not for a single type, for it is produced by members of both the n-3 and n-6 classes of polyunsaturated fatty acids.     

Effect of Polyunsaturated Fatty Acids on Fetal Mouse Brain Cells in Culture in a Chemically Defined Medium

Abstract: The biochemical and morphological effects of polyunsaturated fatty acids on fetal brain cells grown in a chemically defined medium were studied. Fetal brain cells were dissociated from mouse cerebral hemispheres taken on the 16th day of gestation. After cells had grown in chemically defined medium for 8 days, the proportion of polyunsaturated fatty acids of cultured cells was only one-half of that observed at day 0 and about 1.5 times less than that of cells grown in serum-supplemented medium. Fatty acid 20:3(n-9) was present in cultured cells grown in either chemically defined or serum-supple-mented medium. demonstrating the deficiency of essential fatty acids. The reduced amount of polyunsaturated fatty acids in cells grown in the chemically defined medium was balanced by an increase in monounsaturated fatty acids. The saturated fatty acids were not affected. When added at the seeding time, linoleic, linolenic, arachidonic, or docosahexaenoic acid stimulated the proliferation of small dense cells. Besides, we demonstrate that each of the four fatty acids studied was incorporated into phospholipids. Adding fatty acids of the n-6 series increased the content of n-6 fatty acids in the cells, but also provoked an increase in the n-3 fatty acids. Among several combinations of fatty acids, only 20:4 and 22:6, when added to the culture in a ratio of 2:1, restored a fatty acid profile similar to controls (i.e. in vivo tissue taken at post- natal dav 5).     

Liver and heart mitochondria obtained from Adelie penguin (Pygoscelis adeliae) offers high resistance to lipid peroxidation

Lipid peroxidation is generally thought to be a major mechanism of cell injury in aerobic organisms subjected to oxidative stress. All cellular membranes are especially vulnerable to oxidation due to their high concentration of polyunsaturated fatty acids. However, birds have special adaptations for preventing membrane damage caused by reactive oxygen species. This study examines fatty acid profiles and susceptibility to lipid peroxidation in liver and heart mitochondria obtained from Adelie penguin (Pygoscelis adeliae). The saturated fatty acids in these organelles represent approximately 40-50% of total fatty acids whereas the polyunsaturated fatty acid composition was highly distinctive, characterized by almost equal amounts of 18:2 n-6; 20:4 n-6 and 22:6 n-3 in liver mitochondria, and a higher proportion of 18:2 n-6 compared to 20:4 n-6 and 22:6 n-3 in heart mitochondria. The concentration of total unsaturated fatty acids of liver and heart mitochondria was approximately 50% and 60%, respectively, with a prevalence of oleic acid C18:1 n9. The rate C20:4 n6/C18:2 n6 and the unsaturation index was similar in liver and heart mitochondria; 104.33 +/- 6.73 and 100.09 +/- 3.07, respectively. Light emission originating from these organelles showed no statistically significant differences and the polyunsaturated fatty acid profiles did not change during the lipid peroxidation process.     

Modulation of Native TREK-1 and Kv1.4 K<Superscript>+</Superscript> Channels by Polyunsaturated Fatty Acids and Lysophospholipids

The modulation of TREK-1 leak and Kv1.4 voltage-gated K⁺ channels by fatty acids and lysophospholipids was studied in bovine adrenal zona fasciculata (AZF) cells. In whole-cell patch-clamp recordings, arachidonic acid (AA) (1–20 µM) dramatically and reversibly increased the activity of bTREK-1, while inhibiting bKv1.4 current by mechanisms that occurred with distinctly different kinetics. bTREK-1 was also activated by the polyunsaturated cis fatty acid linoleic acid but not by the trans polyunsaturated fatty acid linolelaidic acid or saturated fatty acids. Eicosatetraynoic acid (ETYA), which blocks formation of active AA metabolites, failed to inhibit AA activation of bTREK-1, indicating that AA acts directly. Compared to activation of bTREK-1, inhibition of bKv1.4 by AA was rapid and accompanied by a pronounced acceleration of inactivation kinetics. Cis polyunsaturated fatty acids were much more effective than trans or saturated fatty acids at inhibiting bKv1.4. ETYA also effectively inhibited bKv1.4, but less potently than AA. bTREK-1 current was markedly increased by lysophospholipids including lysophosphatidyl choline (LPC) and lysophosphatidyl inositol (LPI). At concentrations from 1–5 µM, LPC produced a rapid, transient increase in bTREK-1 that peaked within one minute and then rapidly desensitized. The transient lysophospholipid-induced increases in bTREK-1 did not require the presence of ATP or GTP in the pipette solution. These results indicate that the activity of native leak and voltage-gated K⁺ channels are directly modulated in reciprocal fashion by AA and other cis unsaturated fatty acids. They also show that lysophospholipids enhance bTREK-1, but with a strikingly different temporal pattern. The modulation of native K⁺ channels by these agents differs from their effects on the same channels expressed in heterologous cells, highlighting the critical importance of auxiliary subunits and signaling. Finally, these results reveal that AZF cells express thousands of bTREK-1 K⁺ channels that lie dormant until activated by metabolites including phospholipase A₂ (PLA₂)-generated fatty acids and lysophospholipids. These metabolites may alter the electrical and secretory properties of AZF cells by modulating bTREK-1 and bKv1.4 K⁺ channels.     

Self-regulation of membrane fluidity. The effect of saturated normal and methoxy fatty acid supplementation on Tetrahymena membrane physical properties and lipid composition.

Tetrahymena cells elongated and desaturated massive supplements of palmitic or lauric acid at nearly twice the rates employed by unfed cells, thereby maintaining constant the physical properties of their membrane lipids. However, when a mixture of the 9- and 10-monomethoxy derivatives of stearic acid was administered, these compounds were incorporated without further metabolism. The marked fluidizing effect of the phospholipid-bound methoxy-fatty acids elicited an immediate reduction in fatty acid desaturase activity, the pattern of change being very similar to that induced by supplements of polyunsaturated fatty acids. The modulation of fatty acid desaturase activity by methoxy-acids clearly seems to be governed by membrane fluidity rather than by some form of end product inhibition of the type which might have been postulated to explain the similar effect caused by polyunsaturated fatty acids.