Short chain fatty acid inhibition of rat brain Na-K adenosine triphosphatase

The possibility was considered that the sleep-like state seen after injection of short chain fatty acids salts into animals is a result of inhibition of the sodium-potassium activated ATPase. Tris salts of short chain fatty acids inhibited brain Na-K ATPase activity in vitro at concentrations similar to intravenous levels causing narcosis in vivo. The inhibition depended on the logarithm of the concentration of a given acid. The concentration of acid anion which caused 50 per cent inhibition of the enzyme system (I50) was determined for straight and branched chain acids with 4-12 carbon atoms per molecule. The log of I50 concentrations plotted against the number of carbon atoms in the molecule gave a straight line; the inhibitory capacity of an acid increased by a factor of 2.3 for each--CH2--added to the carbon chain. It is suggested that both fatty acid narcosis and the enzyme inhibition result from fatty acid molecules forming an ordered array along the membrane in association with membrane lipids.     

In vitro culture of coconut endosperm: callus induction and its fatty acids

Summary Successful induction of callus from coconut endosperm was achieved by using the tissue situated near the micropylar end of a young fruit. For initiation of callus, a high concentration of auxin (20 to 100 ppm) was added to the basal medium containing activated charcoal. Subcultured callus showed a 40-fold increase during culture of three months. Based on the analysis of fatty acid composition, the maturation of endosperm was characterized by an increase in short chain fatty acids (C₈, C₁₀, C₁₂, C₁₄)and a decrease in long chain fatty acids (C₁₆, C_{18: 1}, C_{18: 2}). In developing endosperms, proportion of short chain fatty acids was higher in lipids of the antipodal than those of other regions. In the final stage of maturation, around 82% of total fatty acids was short chain fatty acids, while the proportion of long chain fatty acids decreased up to 16%. The fatty acid composition of callus subcultured for six months was comparable to that of the immature endosperm. Lipids were accumulated in callus as globular bodies.     

Release of short chain fatty acids from cream lipids by commercial lipases and esterases

Lipases and esterases are frequently used in dairy production processes to enhance the buttery flavour of the end product. Short chain fatty acids, and especially butanoic acid, play a key role in this and different enzymes with specificity towards short chain fatty acids are commercially available as potent flavouring tools. We have compared six lipases/esterases associated with buttery flavour production. Although specificity to short chain fatty acids was ascribed to each enzyme, clear differences in free fatty acid profiles were found when these enzymes were applied on cream. Candida cylindraceae lipase was the most useful enzyme for buttery flavour production in cream with the highest yield of free fatty acids (57 g oleic acid 100 g⁻¹ fat), no release of long chain fatty acids and specificity towards butanoic acid.     

鸡肠道菌群和短链脂肪酸相互关系的研究进展

肠道是动物机体重要的消化和营养吸收器官。肠道菌群决定肠道健康,进而影响机体健康。近年来关于肠道菌群的研究越来越多,且肠道菌群酵解底物产生的短链脂肪酸也备受人们关注。短链脂肪酸主要包括乙酸、丙酸、丁酸等及其盐类。在对肠道功效方面,短链脂肪酸发挥着重要作用,如氧化供能、维持水电解质平衡、调节免疫、抗病原微生物及抗炎、调节肠道菌群平衡、改善肠道功能等。因此,本文根据近年来国内外相关研究报道,综述了鸡肠道不同种类、含量的菌群对短链脂肪酸来源和吸收的影响;不同种类、含量和制剂形态的短链脂肪酸对肠道菌群影响的研究进展,为更好地了解鸡肠道菌群和短链脂肪酸的相互关系和提高禽类养殖水平提供理论指导。     

The effect of dietary and plasma fatty acids on platelet aggregation in senior generation of Japanese women

Dietary factors that influence platelet aggregation have not been fully clarified in humans. 63 Japanese women, aged 40-70 years old, completed one-day weighted dietary records, and received physical and laboratory examinations. Platelet aggregation was measured by 1.0 and 3.0 microM ADP induction. The results were analyzed with special reference to fatty acids. The short and medium chain fatty acid intake showed negative correlation with maximum percent of platelet aggregation induced by 1.0 microM ADP. Short and medium chain fatty acids in this study were mostly derived from milk and dairy products. Importance of short and medium chain fatty acid intake on platelet aggregation requires further study for prevention of cardiovascular diseases.     

Polyphenol fatty acid esters as serine protease inhibitors: a quantum-chemical QSAR analysis

We investigated the ability of polyphenol fatty acid esters to inhibit the activity of serine proteases trypsin, thrombin, elastase and urokinase. Potent protease inhibition in micromolar range was displayed by rutin and rutin derivatives esterified with medium and long chain, mono- and polyunsaturated fatty acids (1e–m), followed by phloridzin and esculin esters with medium and long fatty acid chain length (2a–d, 3a–d), while unmodified compounds showed only little or no effect. QSAR study of the compounds tested provided the most significant parameters for individual inhibition activities, i.e. number of hydrogen bond donors for urokinase, molecular volume for thrombin, and solvation energy for elastase. According to the statistical analysis, the action of elastase inhibitors is opposed to those of urokinase and thrombin. Cluster analysis showed two groups of compounds: original polyphenols together with rutin esters with short fatty acid chain length and rutin esters with long fatty acid chain length.     

Involvement of the acyl chain of ceramide in carbohydrate recognition by an anti-glycolipid monoclonal antibody: the case of an anti-melanoma antibody,M2590, to GM3-ganglioside

The effect of the chain length of the fatty acid residue of the ceramide moiety of ganglioside G_M3 on the binding ability of monoclonal antibody M2590, which is specific for the carbohydrate structure of G_M3-ganglioside, was examined by means of a direct binding assay on thin layer chromatography plates (TLC immunostaining) and a quantitative enzyme-linked immunosorbent assay (ELISA). Derivatives of G_M3 with a long fatty acid chain reacted with the M2590 antibody, but those with a short fatty acid chain showed no reaction in either assay system. These results suggested that the acyl fatty acid moiety of the ganglioside played an important role in the formation or maintenance of the antigenic structure of the carbohydrate moiety of the ganglioside.     

Effects of short chain fatty acids on radicle emergence and root growth in lettuce

Abstract. Short chain fatty acids inhibit both radicle emergence and root growth in lettuce. The transition from ineffectual to inhibitory levels occurs abruptly. Root growth is more sensitive to lower concentrations than radicle emergence and is invariant with chain length. The effect of short chain alcohols on radicle emergence is similar to that of short chain acids, but their comparatively severe inhibition of root growth varies with chain length. Alkanes of the same chain lengths have no noticeable effect. Respiration is not altered by a representative short chain fatty acid (heptanoic). Lettuce seeds are sensitized to phytochrome-absorbed light by short chain fatty acids as found by Berrie and co-workers.     

Effects of short chain fatty acid producing bacteria on epigenetic regulation of FFAR3 in type 2 diabetes and obesity

The human gut microbiota and microbial influences on lipid and glucose metabolism, satiety, and chronic low-grade inflammation are known to be involved in metabolic syndrome. Fermentation end products, especially short chain fatty acids, are believed to engage the epigenetic regulation of inflammatory reactions via FFARs (free fatty acid receptor) and other short chain fatty acid receptors.     

Phase behavior of stratum corneum lipids in mixed Langmuir-Blodgett monolayers.

The lipids found in the bilayers of the stratum corneum fulfill the vital barrier role of mammalian bodies. The main classes of lipids found in stratum corneum are ceramides, cholesterol, and free fatty acids. For an investigation of their phase behavior, mixed Langmuir-Blodgett monolayers of these lipids were prepared. Atomic force microscopy was used to investigate the structure of the monolayers as a function of the monolayer composition. Three different types of ceramide were used: ceramide extracted from pigskin, a commercially available ceramide with several fatty acid chain lengths, and two synthetic ceramides that have only one fatty acid chain length. In pigskin ceramide-cholesterol mixed monolayers phase separation was observed. This phase separation was also found for the commercially available type III Sigma ceramide-cholesterol mixed monolayers with molar ratios ranging from 1:0.1 to 1:1. These monolayers separated into two phases, one composed of the long fatty acid chain fraction of Sigma ceramide III and the other of the short fatty acid chain fraction of Sigma ceramide III mixed with cholesterol. Mixtures with a higher cholesterol content consisted of only one phase. These observations were confirmed by the results obtained with synthetic ceramides, which have only one fatty acid chain length. The synthetic ceramide with a palmitic acid (16:0) chain mixed with cholesterol, and the synthetic ceramide with a lignoceric acid (24:0) chain did not. Free fatty acids showed a preference to mix with one of these phases, depending on their fatty acid chain lengths. The results of this investigation suggest that the model system used in this study is in good agreement with those of other studies concerning the phase behavior of the stratum corneum lipids. By varying the composition of the monolayers one can study the role of each lipid class in detail.     

Aspergillus nidulans contains six possible fatty acyl-CoA synthetases with FaaB being the major synthetase for fatty acid degradation

Aspergillus nidulans can use a variety of fatty acids as sole carbon and energy sources via its peroxisomal and mitochondrial β-oxidation pathways. Prior to channelling the fatty acids into β-oxidation, they need to be activated to their acyl-CoA derivates. Analysis of the genome sequence identified a number of possible fatty acyl-CoA synthetases (FatA, FatB, FatC, FatD, FaaA and FaaB). FaaB was found to be the major long-chain synthetase for fatty acid degradation. FaaB was shown to localise to the peroxisomes, and the corresponding gene was induced in the presence of short and long chain fatty acids. Deletion of the faaB gene leads to a reduced/abolished growth on a variety of fatty acids. However, at least one additional fatty acyl-CoA synthetase with a preference for short chain fatty acids and a potential mitochondrial candidate (AN4659.3) has been identified via genome analysis.     

The peroxisomal Acyl-CoA thioesterase Pte1p from Saccharomyces cerevisiae is required for efficient degradation of short straight chain and branched chain fatty acids

The role of the Saccharomyces cerevisae peroxisomal acyl-coenzyme A (acyl-CoA) thioesterase (Pte1p) in fatty acid beta-oxidation was studied by analyzing the in vitro kinetic activity of the purified protein as well as by measuring the carbon flux through the beta-oxidation cycle in vivo using the synthesis of peroxisomal polyhydroxyalkanoate (PHA) from the polymerization of the 3-hydroxyacyl-CoAs as a marker. The amount of PHA synthesized from the degradation of 10-cis-heptadecenoic, tridecanoic, undecanoic, or nonanoic acids was equivalent or slightly reduced in the pte1Delta strain compared with wild type. In contrast, a strong reduction in PHA synthesized from heptanoic acid and 8-methyl-nonanoic acid was observed for the pte1Delta strain compared with wild type. The poor catabolism of 8-methyl-nonanoic acid via beta-oxidation in pte1Delta negatively impacted the degradation of 10-cis-heptadecenoic acid and reduced the ability of the cells to efficiently grow in medium containing such fatty acids. An increase in the proportion of the short chain 3-hydroxyacid monomers was observed in PHA synthesized in pte1Delta cells grown on a variety of fatty acids, indicating a reduction in the metabolism of short chain acyl-CoAs in these cells. A purified histidine-tagged Pte1p showed high activity toward short and medium chain length acyl-CoAs, including butyryl-CoA, decanoyl-CoA and 8-methyl-nonanoyl-CoA. The kinetic parameters measured for the purified Pte1p fit well with the implication of this enzyme in the efficient metabolism of short straight and branched chain fatty acyl-CoAs by the beta-oxidation cycle.     

3-Hydroxyacyl-CoA dehydrogenase and short chain 3-hydroxyacyl-CoA dehydrogenase in human health and disease

3-Hydroxyacyl-CoA dehydrogenase (HAD) functions in mitochondrial fatty acid beta-oxidation by catalyzing the oxidation of straight chain 3-hydroxyacyl-CoAs. HAD has a preference for medium chain substrates, whereas short chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) acts on a wide spectrum of substrates, including steroids, cholic acids, and fatty acids, with a preference for short chain methyl-branched acyl-CoAs. Therefore, HAD should not be referred to as SCHAD. SCHAD is not a member of the HAD family, but instead, belongs to the short chain dehydrogenase/reductase superfamily. Previously reported cases of SCHAD deficiency are due to an inherited HAD deficiency. SCHAD, also known as 17beta-hydroxysteroid dehydrogenase type 10, is important in brain development and aging. Abnormal levels of SCHAD in certain brain regions may contribute to the pathogenesis of some neural disorders. The human SCHAD gene and its protein product, SCHAD, are potential targets for intervention in conditions, such as Alzheimer's disease, Parkinson's disease, and an X-linked mental retardation, that may arise from the impaired degradation of branched chain fatty acid and isoleucine.     

Significance of lipoidal estradiol in human mammary tumors

Incubations of p-nitrophenyl fatty acyl esters and estradiol-17 beta fatty acyl 17-esters with porcine esterase, human mammary tumor cytosol and rat uterine cytosol leads to ester hydrolysis of compounds with short chain fatty acids. Esters with long chain fatty acids show no hydrolysis except in the presence of Tween 80. Short chain fatty acid esters have a higher binding potency to the estrogen receptor than long chain fatty acid esters. Extraction of the nuclear receptor peak sedimenting at 4.6S and identification of the steroid showed that about 90% of the radioactivity was associated with estradiol and only 10% with estradiol esters. These studies show that estradiol fatty acyl esters act as a storage form from which estradiol is released by enzymatic hydrolysis.     

Sulfatide with short fatty acid dominates in astrocytes and neurons

Glycosphingolipids are located in cell membranes and the brain is especially enriched. We speculated that the subcellular location of glycosphingolipids depends on their fatty acid chain length because their sugar residues are constant, whereas fatty acid chain length can vary within the same molecule. To test this hypothesis we analysed the glycosphingolipid sulfatide, which is highly abundant in myelin and has mostly long fatty acids. We used a negative ion electrospray tandem mass spectrometry precursor ion scan to analyse the molecular species of sulfatide in cultured astrocytes and a mouse model of the human disease metachromatic leukodystrophy. In these arylsulfatase A (ASA)-deficient mice sulfatide accumulates intracellularly in neurons and astrocytes. Immunocytochemistry was also performed on cultured astrocytes and analysed using confocal laser scanning microscopy. Analyses of the molecular species showed that cultured astrocytes contained sulfatide with a predominance of stearic acid (C18), which was located in large intracellular vesicles throughout the cell body and along the processes. The same was seen in ASA-deficient mice, which accumulated a higher proportion (15 mol% compared with 8 mol% in control mice) of sulfatide with stearic acid. We conclude that the major fatty acid composition of sulfatide differs between white and grey matter, with neurons and astrocytes containing mostly short-chain fatty acids with an emphasis on stearic acid. Based on our results, we speculate that the fatty acid chain length of sulfatide might determine its intracellular (short chain) or extracellular (long chain) location and thereby its functions.     

Fatty acid synthesis in aged potato slices

Synthesis of fatty acids has been studied in aged potato slices. Formation of the very long chain fatty acids was inhibited by the presence of fluoride or by high incubation temperatures. Arsenite caused an increase in the percentage incorporation of radioactivity from acetate-[¹⁴C] into palmitic acid, apparently by inhibiting further elongation. The results indicate that the aged potato contains at least three enzymes responsible for saturated fatty acid synthesis, At short incubation times, the newly formed fatty acids were mainly unesterified but later become incorporated into phospholipids. Phosphatidylcholine contained the greatest proportion of radioactive fatty acids. Newly formed polyenoic fatty acids were principally transacylated into phosphatidylcholine and phosphatidylethanolamines. The very long chain fatty acids, on the other hand, were mainly located in the wax ester and unesterified fatty acid fractions, from which they can easily be converted into suberin components.     

Consequences to the Host of Changes in Rumen Microbial Activity

BOTH the microbial species in the rumen and the composition of the short chain fatty acids produced there as waste products of fermentation are influenced by the chemical composition, physical form and, in some circumstances, the amount of the diet. Thus, in cattle receiving barley cubes to 80% of the limit of appetite there was a high proportion of butyric acid in the mixture of short chain fatty acids associated with a large population of ciliate protozoa. With barley cubes given ad libitum there was a high proportion of propionic acid, a reduction in the number of ciliates and an increase in the bacterioides-type rods and certain curved Gram negative rods¹.     

Inhibition of mitochondrial carnitine palmitoyl transferase by 2-tetradecylglycidic acid (McN-3802) (Preliminary Communication)

The oral hypoglycemic agent, 2-tetradecylglycidic acid (McN-3802), which has been reported to inhibit the oxidation of long chain but not short chain fatty acids in isolated rat hepatocytes and muscle preparations, inhibited the oxidation of palmitoyl CoA and palmitic acid by rat liver mitochondria. The drug itself, which is a fatty acid analog, was not oxidized by mitochondria. Evidence is presented that 2-tetradecylglycidic acid (or its coenzyme A ester) inhibits fatty acid oxidation by irreversibly inhibiting mitochondrial carnitine palmitoyltransferase. The drug did not inhibit mitochondrial palmitoyl-CoA synthetase.     

Metabolic carbon fluxes and biosynthesis of polyhydroxyalkanoates in Ralstonia eutropha on short chain fatty acids

Short chain fatty acids such as acetic, propionic, and butyric acids can be synthesized into polyhydroxyalkanoates (PHAs) by Ralstonia eutropha. Metabolic carbon fluxes of the acids in living cells have significant effect on the yield, composition, and thermomechanical properties of PHA bioplastics. Based on the general knowledge of central metabolism pathways and the unusual metabolic pathways in R. eutropha, a metabolic network of 41 bioreactions is constructed to analyze the carbon fluxes on utilization of the short chain fatty acids. In fed-batch cultures with constant feeding of acid media, carbon metabolism and distribution in R. eutropha were measured involving CO2, PHA biopolymers, and residual cell mass. As the cells underwent unsteady state metabolism and PHA biosynthesis under nitrogen-limited conditions, accumulative carbon balance was applied for pseudo-steady-state analysis of the metabolic carbon fluxes. Cofactor NADP/NADPH balanced between PHA synthesis and the C3/C4 pathway provided an independent constraint for solution of the underdetermined metabolic network. A major portion of propionyl-CoA was directed to pyruvate via the 2-methylcitrate cycle and further decarboxylated to acetyl-CoA. Only a small amount of propionate carbon (<15% carbon) was directly condensed with acetyl-CoA for 3-hydroxyvalerate. The ratio of glyoxylate shunt to TCA cycle varies from 0 to 0.25, depending on the intracellular acetyl-CoA level and acetic acid in the medium. Malate is the node of the C3/C4 pathway and TCA cycle and its decarboxylation to dehydrogenation ranges from 0.33 to 1.28 in response to the demands on NADPH and oxaloacetate for short chain fatty acids utilization.