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Study by X-ray diffraction of the geometrical shape of glycoprotein sugar chains in two model glycoconjugates, a liposaccharide and a phospholiposaccharide, having the same sugar chain.

Two amphipatic, model glycoconjugates having the same sugar chain but differing in their hydrophobic component were studied by X-ray diffraction in concentrated water solution and in the dry state. The liposaccharide 2, obtained by linking the NH2-4 group of the asparagine residue of the glycoaminoacid obtained from hen ovotransferrin with the activated carboxylic acid group of palmitic acid exhibited a cubic structure in which the sugar chain adopted a slightly deformed, "T-shaped conformation". The phospholiposaccharide 3, obtained by linking the NH2-4 group of the asparagine residue of the same glycoamino acid with the primary amine group of dipalmitoylphosphatidylethanolamine through a suberyl bridge exhibited a lamellar structure in which the sugar chain adopted a "Y-shaped conformation". Thus, it was possible to induce a conformational change of the hen ovotransferrin sugar chain by changing the "hydrophobic residue" to which it is linked.

Animals↗

A more detailed fatty acid composition of human lipoprotein(a)--a comparison with low density lipoprotein.

Lipoprotein(a)'s (Lp(a)'s) fatty acid composition is partially known for the cholesteryl ester (CE), triglyceride (TG) and total phospholipid (PL) fractions. Individual PLs' fatty acids are unknown. This study sought to confirm and extend existing data and elucidate the individual PLs of Lp(a). For Lp(a) versus LDL, the mole percentage saturated fatty acids comprised 11.3+/-1.3 versus 16.8+/-1.2 (CE) (P<0.05), 43.4+/-5.2 versus 39.2+/-4.0 (TG) (P<0.05), 55.7+/-6.3 versus 54.7+/-5.9 (PL) (P>0.05), 51.9+/-3.5 versus 50.2+/-4.2 (choline-containing phospholipids (PC)) (P>0.05), 40.2+/-4.6 versus 43.1+/-3.9 (ethanolamine-containing phospholipids (PE)) (P>0.05), 73.2+/-7.6 versus 81.2+/-8.2 (sphingomyelin (SPH)) (P<0.05). Linoleic acid was CE's major fatty acid and while palmitic acid was the major fatty acid in all other fractions except PE.

Adult↗

Dietary docosahexaenoic acid protects against N-methyl-N-nitrosourea-induced retinal degeneration in rats.

The effect of dietary intake of specific types of fatty acids on retinal degeneration due to N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell apoptosis was evaluated. Fifty-day-old female Sprague-Dawley rats were given a single intraperitoneal injection of 50 mg kg(-1) body weight of MNU, and were then switched to one of five different diets containing the following fatty acids at the following weight percentages: 10% linoleic acid (LA); 9.5% palmitic acid (PA) and 0.5% LA; 9.5% eicosapentaenoic acid (EPA) and 0.5% LA; 4.75% EPA, 4.75% docosahexaenoic acid (DHA) and 0.5% LA; or 9.5% DHA and 0.5% LA. When rats developed MNU-induced mammary tumors with a diameter of > or =1 cm, or at the termination of the experiment (20 weeks after MNU injection), retinal tissue samples were obtained and examined. Incidence and severity of retinal damage were compared by histologic examination. MNU-induced retinal degeneration was prevented in rats fed the diet containing 9.5% DHA (4.75% DHA was less effective), whereas it was accelerated in rats fed the 10% LA diet. Over the course of the 20-week experimental period, the fatty acid composition of serum reflected differences in dietary fatty acids. The present results indicate that a diet containing 9.5% DHA can counteract MNU retinotoxicity in the rat retina. DHA may play a role in protection against MNU-induced photoreceptor cell apoptosis in the rat retina.

Alkylating Agents↗

Serotonin fails to induce proliferation of endothelial cells preloaded with eicosapentaenoic acid and docosahexaenoic acid.

Diets rich in fish oils are associated with a reduced risk of cardiovascular disease including reduction of atherosclerosis and restenosis. We examined the effect of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), major components of fish oils, on serotonin (5HT) stimulated vascular endothelial cells proliferation as a possible mechanism for this vascular protective effect. In this study we demonstrate that 5HT, a known mitogen for vascular endothelial cells, failed to stimulate proliferation of endothelial cells pre-incubated with EPA and DHA. This inhibitory effect was specific for omega-3 fatty acids only and not shared by other fatty acids like oleic acid (monounsaturated) or arachidonic acid (polyunsaturated) or palmitic acid (saturated). When endothelial cells were exposed to EPA and DHA in the ratio present in fish oils, EPA and DHA were shown to act synergistically in inhibiting the proliferative effect of 5HT. These results suggests that one of the mechanisms by which fish oils may confer vascular protective effect is by making the endothelial cells less responsive to mitogenic stimuli of growth factors such as 5HT that are released by aggregating platelets at sites of vascular injury. This inhibition of endothelial cell proliferation may account for the clinically observed effects of fish oil in attenuating the progression of atherosclerotic changes or neointimal proliferation following vascular injury.

Animals↗

Mass spectrometric methods prove the use of beeswax and ruminant fat in late Roman cooking pots.

Lipid extracts of sherds of archaeological late Roman cooking pots were analysed using high temperature-gas chromatography coupled to a mass spectrometer and liquid chromatography with atmospheric pressure chemical ionization mass spectrometer detection (LC-APCI-MS). With these advanced techniques the use of beeswax was shown through identification of the constituting alkanes, mono and diesters. The detection of high amounts of saturated triacylglycerols (TAGs) further indicated that animal fat was processed in these pots. Part of the animal fat was characterised as originating from ruminants due to the presence of trans-fatty acids. The distribution of saturated TAGs and the higher concentration of stearic acid compared to palmitic acid in the transesterified lipid extract indicated that this was sheep fat. The results illustrate how complex mixtures can be unravelled and original contents of ancient ceramic vessels can be determined using specialised analytical equipment.

Animals↗

Inhibition and regulation of rat liver L-threonine dehydrogenase by different fatty acids and their derivatives.

Rat liver L-threonine dehydrogenase is a mitochondrial enzyme which transforms L-threonine either into aminoacetone or into acetyl-CoA. We show that it is inhibited by several fatty acids and their derivatives: short chain fatty acids, L-2-hydroxybutyrate and D-3-hydroxybutyrate, long chain fatty acids, such as lauric acid, myristic acid, palmitic and stearic acids, bicarboxylic acids such as malonic acid and its derivatives methyl- and hydroxymalonic acids. The inhibition occurs at low and physiological concentrations of such compounds, which are normally present and metabolized in mitochondria. It presumably plays a role in the physiology of acetyl-CoA-dependent formation of fatty acids and ketobodies, in L-threonine-dependent gluconeogenesis, and in the regulation of L-threonine metabolism by L-threonine dehydrogenase and L-threonine deaminase.

3-Hydroxybutyric Acid↗

[Changes in the erythrocyte membrane during blood preservation. Influence of progesterone].

Modifications of the erythrocyte membrane during blood conservation are studied. The functional condition of the membrane was observed by means of the biosynthesis of lecithines; modifications occurring at the level of the composition of the membrane proteins were then looked for. The study has been carried out on fresh blood and on blood stroed for 8 days, 15 days, 29 days and 43 days. Another series of assays has been done on stored blood in the presence of progesterone after the same conservation periods. The metabolic activity of the membrane, in the lecithine biosynthesis is studied by measuring the incorporation of fatty acid in the lysolecithines when the membrane is incubated in the presence of linoleic acid or [14] palmitic acid and coenzyme A, or in the presence of [14C] palmitoyl coenzyme A. Variations have been observed during blood conservation: the incorporation or radioactive fatty acid increases during the first 15 days of conservation, then it decreases to a value nearing the original value after 43 days. When the blood is stored in the presence of progesterone (1,6 mumole/1) a more stable incorporation of the fatty acid is observed; variations during conservation are weaker than without progesterone. Membrane proteins have been studied by electrophoresis on polyacrylamide gel after solubilisation by sodium dodecyl sulfate. The intensity of protein zones after coloring, decreases during conservation especially in proteins with a high molecular weight. A quantitative study has been made by chromatography on Sephadex G200 of dansylated proteins with a fluorimetric dosage. In the presence of progesterone, the decrease of the rate of proteins with a high molecular weight is weaker. Therefore, progesterone is proved to allow a better conservation of erythrocyte membrane proteins. As a conclurion, the results of these works show a positive action of progesterone on the erythrocyte membrane during blood conservation.

Blood Preservation↗

Oleic acid-induced Ca2+ mobilization in human platelets: is oleic acid an intracellular messenger?

The purpose of this study was to explore the effect of oleic acid (OA) on intracellular Ca2+ mobilization in human platelets. When applied extracellularly, OA produced a concentration dependent rise in cytosolic [Ca2+] ([Ca2+]cyt) when extracellular [Ca2+] (Ca2+]ext) was zero (presence of EGTA), suggesting that OA caused an intracellular release of Ca2+. Intracellular Ca2+ release was directly proportional to entry of OA into platelets and OA entry was indirectly proportional to [Ca2+]ext. In permeabilized platelets, OA caused the release of 45Ca2+ from ATP dependent intracellular stores. Finally, our results show that thrombin stimulated the release of [3H]OA from platelet phospholipids. The saturated fatty acids stearic and palmitic acid did not stimulate an increase in [Ca2+]cyt under these conditions, but the unsaturated fatty acid, linolenic acid produced effects similar to those of OA, suggesting specificity among fatty acids for effects on [Ca2+]cyt. Taken together, our experiments suggest that OA which has been incorporated into platelet phospholipids was released into the cytosol by thrombin stimulation. Our experiments also show that OA stimulates Ca2+ release from intracellular stores. These results support the hypothesis that OA may serve as an intracellular messenger in human platelets.

Blood Platelets↗

Effect of season on the fatty acid composition and free amino acid content of the sardine Sardinops melanostictus.

The purpose of this study was to clarify the seasonal variation of fatty acid composition and free amino acid content in the Japanese sardine (Sardinops melanostictus) from the sea of Hyuga-Nada, and the relationship between the fatty acid composition of this sardine and that of plankton in the area. The lipid content of sardines at the sea of Hyuga-Nada was low in February (1.8%) and high (7.2%) from July to September. The major fatty acids in the total lipids from sardine were myristic acid (14:0), palmitic acid (16:0), stearic acid (18:0), palmitoleic acid (16:1 n-7), oleic acid (18:1 n-9), eicosapentaenoic acid (20:5 n-3), and docosahexaenoic acid (22:6 n-3). The characteristics of the fatty acids isolated from sardines in July were similar to those from plankton in the same season. This reflects the deposition of plankton fatty acids in sardine depot fat. The season of high free histidine content in the ordinary meat corresponded with that of high lipid content. These results suggested that both the fatty acid composition of sardines and the high concentrations of certain amino acids in free form are influenced by the intake and seasonal variation of composition of plankton.

Amino Acids↗

Determination of total long-chain fatty acids in human plasma and lipoproteins, before and during copper-stimulated oxidation, by high-performance liquid chromatography.

An improved method for the high-performance liquid chromatographic determination (HPLC) of total or free long-chain (> C12) fatty acids in small volumes (10 microL) of human plasma and lipoprotein samples is described. The method is based on the formation of 2-nitrophenyl-hydrazine (2-NPH) derivatives and offers an alternative to gas chromatographic (GC) fatty acid determination. The retention of 2-NPH fatty acid derivatives on the HPLC system differs from the typical pattern produced by GC separation, thus offering a powerful tool for confirmation of peak identification where GC peak resolution is poor. Fatty acids determined include saturates [myristic acid, C14:0; palmitic acid, C16:0; stearic acid, C18:0; eicosanoic acid, C20:0; docosanoic acid, C22:0; and tetracosanoic acid, C24:0], monounsaturates [palmitoleic, C16:1; petroselenic, C18:1n12; oleic, C18:1n9; and erucic, C22:1], and polyunsaturates [linoleic, C18:2; linolenic, C18:3n3; gamma-linolenic acid, C18:3n6; eicosatrienoic, C20:3; arachidonic, C20:4; eicosapentanoic, C20:5; docosahexanoic, C20:6; and docosatetraenoic, C22:4]. Mean recoveries of fatty acids added to LDL samples were 94.1-109.4%, and intraassay coefficients of variation for the major fatty acids in human plasma were 2.7-6.9%. The potential of the method for further development is discussed. Long-chain fatty acid profiles are given for plasma and very low-, low, and high-density lipoprotein (before and during copper-stimulated oxidation) from human blood.

Chromatography, High Pressure Liquid↗

Simultaneous lipidation of a characterized peptide mixture by chemoselective ligation.

The modification of a peptide antigen by a fatty acid such as palmitic acid is now recognized as a mean to induce cellular responses. Mixtures of lipopeptides, obtained by combining individually synthesized compounds, were shown to be promising synthetic vaccine candidates. Usually, in lipopeptide synthesis, the fatty acyl moiety is introduced on the crude peptide chain using solid-phase methods. The separation of the target compound from impurities by RP-HPLC is often complicated by the amphiphilic properties of lipopeptides and results in low overall yields. To overcome the difficulties associated with lipopeptide synthesis and mixture preparation, we have developed a method where the fatty acyl moiety is site-specifically and collectively introduced in solution onto a mixture of individually prepurified peptides. The lipidation is based on the quasistoichiometric and high-yielding ligation of a glyoxylyl lipid with hydrazinoacetyl peptides. The hydrazone constructs were prepared in a salt-free medium and could be isolated by direct lyophilization of the reaction mixture. This process is compatible with cysteinyl peptides, and no aggregation nor degradation could be observed.

Amino Acid Sequence↗

Oil goldenberry (Physalis peruviana L.).

Whole berries, seeds, and pulp/peel of goldenberry (Physalis peruviana L.) were compared in terms of fatty acids, lipid classes, triacylglyerols, phytosterols, fat-soluble vitamins, and beta-carotene. The total lipid contents in the whole berries, seeds, and seedless parts were 2.0, 1.8, and 0.2% (on a fresh weight basis), respectively. Linoleic acid was the dominating fatty acid followed by oleic acid as the second major fatty acid. Palmitic and stearic acids were the major saturates. In pulp/peel oil, the fatty acid profile was characterized by higher amounts of saturates, monoenes, and trienes than in whole berry and seed oils. Neutral lipids comprised >95% of total lipids in whole berry oil and seed oil, while neutral lipids separated in lower level in pulp/peel oil. Triacylglycerols were the predominant neutral lipid subclass and constituted ca. 81.6, 86.6, and 65.1% of total neutral lipids in whole berry, seed, and pulp/peel oils, respectively. Nine triacylglycerol molecular species were detected, wherein three species, C54:3, C52:2, and C54:6, were presented to the extent of approximately 91% or above. The highest level of phytosterols was estimated in pulp/peel oil that contained the highest level of unsaponifiables. In both whole berry and seed oils, campesterol and beta-sitosterol were the sterol markers, whereas Delta5-avenasterol and campesterol were the main 4-desmethylsterols in pulp/peel oil. The tocopherols level was much higher in pulp/peel oil than in whole berry and seed oils. beta- and gamma-tocopherols were the major components in whole berry and seed oils, whereas gamma- and alpha-tocopherols were the main constituents in pulp/peel oil. beta-Carotene and vitamin K(1) were also measured in markedly high levels in pulp/peel oil followed by whole berry oil and seed oil, respectively. Information provided by the present work is of importance for further chemical investigation of goldenberry oil and industrial utilization of the berries as a raw material of oils and functional foods.

Fatty Acids↗

Isolation and characterization of neutral lipids of desilked eri silkworm pupae grown on castor and tapioca leaves.

The neutral lipid of desilked eri silkworm pupae (Samia cynthia ricini) grown on two different host plants, castor (Ricinus communis Linn.) and tapioca (Manihot utilizsima Phol.) leaves, was extracted with hexane. The oil content in pupae was estimated to be in the range of 18-20% (dry basis). The pupal oil was found to be enriched with alpha-linolenic acid (ALA) with palmitic acid as the second major fatty acid. The level of ALA in the oil of silkworm pupae was found to be significantly higher (P < 0.001) when grown on tapioca (58.3%) as compared to those grown on castor (42.9%). Other chemical parameters such as percent free fatty acid, peroxide value, phosphorus content, percent unsaponifiable matter, and composition of sterols were also determined in both of the oils and compared. Reversed-phase high-performance liquid chromatography analysis of triacylglycerol molecular species showed that the pupal oil is rich in molecular species with equivalent carbon numbers (ECN) C36, C40, C42, C44, and C48. There was a significantly higher level (P < 0.001) of trilinolenin (C36) in the oil of tapioca-based silkworm as compared to castor-based silkworm pupae. Regiospecific analysis of the oil showed a higher level of ALA at the sn-2 position of silkworm pupae grown on tapioca (60.2%) as compared to those grown on castor (47.3%) oil. Thus, the presence of a large amount of ALA and their predominance at the sn-2 position make the eri pupal oil highly nutritious, provided that the oxidative stability is ensured.

Animals↗

Phytochemical and nutrient composition of the freeze-dried amazonian palm berry, Euterpe oleraceae mart. (acai).

Euterpe oleraceae is a large palm tree indigenous to the Amazon River and its tributaries and estuaries in South America. Its fruit, known as acai, is of great economic value to native people. In this study, a standardized freeze-dried acai fruit pulp/skin powder was used for all analyses and tests. Among many findings, anthocyanins (ACNs), proanthocyanidins (PACs), and other flavonoids were found to be the major phytochemicals. Two ACNs, cyandin 3-glucoside and cyanidin 3-rutinoside were found to be predominant ACNs; three others were also found as minor ACNs. The total content of ACNs was measured as 3.1919 mg/g dry weight (DW). Polymers were found to be the major PACs. The concentration of total PACs was calculated as 12.89 mg/g DW. Other flavonoids, namely, homoorientin, orientin, isovitexin, scoparin, and taxifolin deoxyhexose, along with several unknown flavonoids, were also detected. Resveratrol was found but at a very low concentration. In addition, components including fatty acids, amino acids, sterols, minerals, and other nutrients were analyzed and quantified. Total polyunsaturated fatty acid, total monounsaturated fatty acid, and total saturated fatty acids contributed to 11.1%, 60.2%, and 28.7% of total fatty acid. Oleic acid (53.9%) and palmitic acid (26.7%) were found to be the two dominant fatty acids. Nineteen amino acids were found; the total amino acid content was determined to be 7.59% of total weight. The total sterols accounted for 0.048% by weight of powder. The three sterols B-sitosterol, campesterol, and sigmasterol were identified. A complete nutrient analysis is also presented. Microbiological analysis was also performed.

Amino Acids↗

Effects of roasting on pyrazine contents and oxidative stability of red pepper seed oil prior to its extraction.

Red pepper seeds were roasted with constant stirring for 6, 9, 10, and 12 min at 210 degrees C, and oils were extracted from the roasted red pepper seeds using an expeller. The iodine values and fatty acid compositions of red pepper seed oils did not change with roasting time. The fatty acid composition of the oil obtained from the red pepper seeds roasted for 6 min was 0.24% myristic acid, 13. 42% palmitic acid, 0.33% palmitoleic acid, 2.07% stearic acid, 10. 18% oleic acid, 73.89% linoleic acid, and 0.37% linolenic acid, showing a fatty acid composition similar to that of high-linoleate safflower oil. Thirteen alkylpyrazines were identified in the roasted red pepper seed oils: 2-methylpyrazine, 2,5-dimethylpyrazine, 2,6-dimethylpyrazine, 2-ethylpyrazine, 2-ethyl-6-methylpyrazine, 2-ethyl-5-methylpyrazine, trimethylpyrazine, 2,6-diethylpyrazine, 2-ethyl-3,5-dimethylpyrazine, tetramethylpyrazine, 2, 3-diethyl-5-methylpyrazine, 2-isobutyl-3-methylpyrazine, and 3, 5-diethyl 2-methylpyrazine. The pyrazine content increased markedly as the roasting time increased, showing 2.63, 5.01, 8.48, and 13.10 mg of total pyrazine/100 g of oils from the red pepper seeds roasted for 6, 8, 10, and 12 min, respectively, at 210 degrees C. 2, 5-Dimethylpyrazine in the roasted red pepper seed oil seemed to be the component most responsible for the pleasant nutty aroma of the oils. The oxidative stabilities of oils increased greatly as the roasting time increased.

Capsicum↗

Characterization of rat testes mitochondrial retinoylating system and its partial purification.

Retinoylation (retinoic acid acylation), a posttranslational modification of proteins occurring in a variety of eukariotic cell lines both in vivo and in vitro, was studied in rat testes mitochondria. all-trans-Retinoic acid, a highly active form of vitamin A in inducing cellular differentiation, is incorporated covalently into proteins of rat testes mitochondria. The maximum retinoylation activity of rat testes mitochondrial proteins was 21.6 pmoles mg protein(-1) 90 min(-1) at 37 degrees C. The activation energy was 44 kJ mol(-1) from 5 to 37 degrees C. The retinoylation activity had a pH optimum of 7.5. The retinoylation process was specific for the presence of ATP, ADP, and GTP (even if only 30% of the control). The half saturation constant (Km) was 0.69 microM for all-trans-retinoic acid, while the inhibition constant (Ki) was 1.5 microM for 13-cis-retinoic acid. Retinoylation was not inhibited by high concentrations of myristic acid (MA) and palmitic acid (PA), indicating that retinoylation and acylation reactions involved different rat testes mitochondrial proteins. The ATP or CoASH saturation curves of retinoylation reaction showed sigmoidal behavior with apparent half saturation constants (K0.5) of 6.5 mM ATP and 40.6 microM CoASH. On SDS-gel electrophoresis, the hydroxylapaptite/celite eluate showed various protein bands between 25 and 80 kDa. This retinoylated protein was purified 17-fold with respect to the mitochondrial extract.

Acylation↗

[Alpine cheese--healthy for your heart or just a lifestyle product?].

Until the 19th and the early 20th century, milk and milk products, particularly of alpine origins, seemed of special nutritional and health value and were highly recommended for the therapy resp. the therapeutic adjunct of various diseases, particularly for pulmonary tuberculosis. More recently, the association of saturated fat intake and arteriosclerosis led to the reduced use of milk and cheese resp. to the introduction of low-fat milk products. Again, alpine milk and cheese seem to differ somewhat from the others, since they appear to contain 4 times more alpha linolenic acid, three times more conjugated linoleic acid, a lower n-6:n-3 ratio, more total n-3 fatty acids and less palmitic acid as a measure of total saturated fat compared to cheese produced with silage feed in the lowlands (e.g. english cheddar). Even cheese from cows fed with linseed supplementations did not reach the n-3 concentrations of the alpine probes. Thus, alpine milk products from cows kept traditionally, and fed predominantly with alpine grass seem to have an interesting cardiovascular and possibly an economically favourable potential.

Altitude↗

Docosahexaenoic acid and other fatty acids induce a decrease in pHi in Jurkat T-cells.

1. Docosahexaenoic acid (DHA) induced rapid (t1/2=33 s) and dose-dependent decreases in pHi in BCECF-loaded human (Jurkat) T-cells. Addition of 5-(N,N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger, prolonged DHA-induced acidification as a function of time, indicating that the exchanger is implicated in pHi recovery. 2. Other fatty acids like oleic acid, arachidonic acid, eicosapentaenoic acid, but not palmitic acid, also induced a fall in pHi in these cells. 3. To assess the role of calcium in the DHA-induced acidification, we conducted experiments in Ca2+-free (0% Ca2+) and Ca2+-containing (100% Ca2+) buffer. We observed that there was no difference in the degree of DHA-induced transient acidification in both the experimental conditions, though pHi recovery was faster in 0% Ca2+ medium than that in 100% Ca2+ medium. 4. In the presence of BAPTA, a calcium chelator, a rapid recovery of DHA-induced acidosis was observed. Furthermore, addition of CaCl2 into 0% Ca2+ medium curtailed DHA-evoked rapid pHi recovery. In 0% Ca2+ medium, containing BAPTA, DHA did not evoke increases in [Ca2+]i, though this fatty acid still induced a rapid acidification in these cells. These observations suggest that calcium is implicated in the long-lasting DHA-induced acidosis. 5. DHA-induced rapid acidification may be due to its deprotonation in the plasma membrane (flip-flop model), as suggested by the following observations: (1) DHA with a -COOH group induced intracellular acidification, but this fatty acid with a -COOCH3 group failed to do so, and (2) DHA, but not propionic acid, -induced acidification was completely reversed by addition of fatty acid-free bovine serum albumin in these cells. 6. These results suggest that DHA induces acidosis via deprotonation and Ca2+ mobilization in human T-cells.

Docosahexaenoic Acids↗