Elongation Of Unsaturated Fatty Acids Research Articles

Multi-omic analysis reveals that Bacillus licheniformis enhances pekin ducks growth performance via lipid metabolism regulation.

Introduction: Bacillus licheniformis (B.licheniformis) was widely used in poultry feeds. However, it is still unclear about how B.licheniformis regulates the growth and development of Pekin ducks. Methods: The experiment was designed to clarify the effect and molecular mechanism of B. licheniformis on the lipid metabolism and developmental growth of Pekin ducks through multiomics analysis, including transcriptomic and metabolomic analyses. Results: The results showed that compared with the control group, the addition of 400 mg/kg B. licheniformis could significantly increase the body weight of Pekin ducks and the content of triglyceride (p < 0.05), at the same time, the addition of B. licheniformis could affect the lipid metabolism of liver in Pekin ducks, and the addition of 400 mg/kg B. licheniformis could significantly increase the content of lipoprotein lipase in liver of Pekin ducks. Transcriptomic analysis revealed that the addition of B. licheniformis primarily impacted fatty acid and glutathione, amino acid metabolism, fatty acid degradation, as well as biosynthesis and elongation of unsaturated fatty acids. Metabolomic analysis indicated that B. licheniformis primarily affected the regulation of glycerol phospholipids, fatty acids, and glycerol metabolites. Multiomics analysis demonstrated that the addition of B. licheniformis to the diet of Pekin ducks enhanced the regulation of enzymes involved in fat synthesis via the PPAR signaling pathway, actively participating in fat synthesis and fatty acid transport. Discussion: We found that B. licheniformis effectively influences fat content and lipid metabolism by modulating lipid metabolism-associated enzymes in the liver. Ultimately, this study contributes to our understanding of how B. licheniformis can improve the growth performance of Pekin ducks, particularly in terms of fat deposition, thereby providing a theoretical foundation for its practical application. Conclusion: B. licheniformis can increase the regulation of enzymes related to fat synthesis through PPAR signal pathway, and actively participate in liver fat synthesis and fatty acid transport, thus changing the lipid metabolism of Pekin ducks, mainly in the regulation of glycerol phospholipids, fatty acids and glycerol lipid metabolites.

Docking studies of flavonoid compounds as inhibitors of β-ketoacyl acyl carrier protein synthase I (Kas I) of Escherichia coli

Escherichia coli is one of the most frequent causes of many common bacterial infections, including cholecystitis, bacteremia, cholangitis, urinary tract infection (UTI), traveler’s diarrhea and other clinical infections such as neonatal meningitis and pneumonia. The fatty acid biosynthesis is essential for the bacterial viability and growth. There are three types of β-ketoacyl acyl carrier protein synthase (KAS) which are important for overcoming the bacterial resistance problem. β-ketoacyl acyl carrier protein synthase I (KAS I) is member of the condensing enzyme family, which is a key catalyst in bacterial fatty acid biosynthesis, and thus an attractive target for novel antibioticsis related to the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and can be a good therapeutic target of designing novel antibiotics. In this report, we performed docking study of E. coli (KAS I) and 50 flavonoids. Out of these 50 flavonoids, there are two compounds, genistein and isorhamnetin, that showed the superior binding energy while fully satisfying the conditions of drug likeliness. The predicted binding energy of genistein and isorhamnetin toward KAS I are −135.76kcal/mol and −132.42kcal/mol, respectively. These energies favorably compare to the biding energy of known drugs thiolactomicin and cerulenin that are −90.26kcal/mol and −99.64kcal/mol, respectively. The method used was docking with the selected E. coli (KAS I-PDB ID-1FJ4) using iGemdock. This was also found to obey the Lipinski’s guidelines of five and to show the drug likeliness and bioavailability.

Antimicrobial Flavonoid, 3,6-Dihydroxyflavone, Have Dual Inhibitory Activity against KAS III and KAS I

Three types of -ketoacyl acyl carrier protein synthase (KAS) are important for overcoming the bacterial resistance problem. Recently, we reported the discovery of a antimicrobial flavonoid, YKAF01 (3,6-dihydroxyflavone), which exhibits antibacterial activity against Gram-positive bacteria through inhibition of -ketoacyl acyl carrier protein synthase III (KAS III). In this report, we suggested that YKAF01 can be an inhibitor -ketoacyl acyl carrier protein synthase I (KAS I) with dual inhibitory activity for KAS I as well as KAS III. KAS I is related to the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and can be a good therapeutic target of designing novel antibiotics. We performed docking study of Escherichia coli KAS I (ecKAS I) and YKAF01, and determined their binding model. YKAF01 binds to KAS I with high binding affinity () and exhibited an antimicrobial activity against the multidrug-resistant E. coli with minimal inhibitory concentration (MIC) value of 512 /mL. Further optimization of this compound will be carried out to improve its antimicrobial activity and membrane permeability against bacterial cell membrane.

Elo1p-dependent carboxy-terminal elongation of C14:1Delta(9) to C16:1Delta(11) fatty acids in Saccharomyces cerevisiae.

Saccharomyces cerevisiae medium-chain acyl elongase (ELO1) mutants have previously been isolated in screens for fatty acid synthetase (FAS) mutants that fail to grow on myristic acid (C14:0)-supplemented media. Here we report that wild-type cells cultivated in myristoleic acid (C14:1Delta(9))-supplemented media synthesized a novel unsaturated fatty acid that was identified as C16:1Delta(11) fatty acid by gas chromatography-mass spectroscopy. Synthesis of C16:1Delta(11) was dependent on a functional ELO1 gene, indicating that Elo1p catalyzes carboxy-terminal elongation of unsaturated fatty acids (alpha-elongation). In wild-type cells, the C16:1Delta(11) elongation product accounted for approximately 12% of the total fatty acids. This increased to 18% in cells that lacked a functional acyl chain desaturase (ole1Delta mutants) and hence were fully dependent on uptake and elongation of C14:1. The observation that ole1Delta mutant cells grew almost like wild type on medium supplemented with C14:1 indicated that uptake and elongation of unsaturated fatty acids were efficient. Interestingly, wild-type cells supplemented with either C14:1 or C16:1 fatty acids displayed dramatic alterations in their phospholipid composition, suggesting that the availability of acyl chains is a dominant determinant of the phospholipid class composition of cellular membranes. In particular, the relative content of the two major phospholipid classes, phosphatidylethanolamine and phosphatidylcholine, was strongly dependent on the chain length of the supplemented fatty acid. Moreover, analysis of the acyl chain composition of individual phospholipid classes in cells supplemented with C14:1 revealed that the relative degree of acyl chain saturation characteristic for each phospholipid class appeared to be conserved, despite the gross alteration in the cellular acyl chain pool. Comparison of the distribution of fatty acids that were taken up and elongated (C16:1Delta(11)) to those that were endogenously synthesized by fatty acid synthetase and then desaturated by Ole1p (C16:1Delta(9)) in individual phospholipid classes finally suggested the presence of two different pools of diacylglycerol species. These results will be discussed in terms of biosynthesis of different phospholipid classes via either the de novo or the Kennedy pathway.

The use of a hybrid genetic system to study the functional relationship between prokaryotic and plant multi-enzyme fatty acid synthetase complexes

Fatty acid synthesis in bacteria and plants is catalysed by a multi-enzyme fatty acid synthetase complex (FAS II) which consists of separate monofunctional polypeptides. Here we present a comparative molecular genetic and biochemical study of the enoyl-ACP reductase FAS components of plant and bacterial origin. The putative bacterial enoyl-ACP reductase gene (envM) was identified on the basis of amino acid sequence similarities with the recently cloned plant enoyl-ACP reductase. Subsequently, it was unambiguously demonstrated by overexpression studies that the envM gene encodes the bacterial enoyl-ACP reductase. An anti-bacterial agent called diazaborine was shown to be a specific inhibitor of the bacterial enoyl-ACP reductase, whereas the plant enzyme was insensitive to this synthetic antibiotic. The close functional relationship between the plant and bacterial enoyl-ACP reductases was inferred from genetic complementation of an envM mutant of Escherichia coli. Ultimately, envM gene-replacement studies, facilitated by the use of diazaborine, demonstrated for the first time that a single component of the plant FAS system can functionally replace its counterpart within the bacterial multienzyme complex. Finally, lipid analysis of recombinant E. coli strains with the hybrid FAS system unexpectedly revealed that enoyl-ACP reductase catalyses a rate-limiting step in the elongation of unsaturated fatty acids.

Effect of eicosatetraynoic acid on liver and plasma lipids.

Groups of rats were fed a fat-free diet supplemented with 0.5% safflower oil (control) or the control diet containing 0.5% of 5,8,11,14-eicosatetraynoic acid (TYA). Blood was collected weekly and plasma lipids analyzed. After 4 weeks, the animals were killed and the liver lipids were analyzed in detail. The acetylenic fatty acid perturbed plasma neutral lipid and phospholipid class concentrations and reduced growth rates. Liver triglyceride concentrations were reduced dramatically in the TYA fed animals, suggesting interference with complex lipid synthesis. Plasma and liver triglycerides were shifted to higher molecular weight species suggesting that TYA affected fatty acid metabolism. The phospholipids showed an accumulation of 18:2 and a fall in 20:4 percentages indicating an inhibition in the conversion of linoleate to arachidonate. All major lipid classes exhibited an increase in 18:1 levels. Analysis of the octadecenoate positional isomers indicated the proportion of oleate increased substantually in all lipid classes whereas vaccenate proportions had fallen dramatically. All of the data collectively suggest that TYA inhibits the elongation of unsaturated fatty acids. A group of rats bearing hepatoma 7288CTC were also fed the TYA diet. Host liver lipids were affected by TYA similar to normal TYA fed animals, but the effects on hepatoma lipids were marginal.

Desaturation and elongation of unsaturated fatty acids in hepatocytes from thermally acclimated rainbow trout

Hepatocytes isolated from 5- and 20 °C-acclimated rainbow trout ( Salmo gairdneri) were incubated with [1- 14C]oleic, -linoleic, or -linolenic acid to investigate the role of desaturation and elongation pathways in cold adaptation. Cells from both acclimation groups demonstrated a substrate preference in the order: 18:3 > 18:2 > 18:1. When assayed at 5 °C, cells from cold-acclimated trout were more efficient at producing derivatives of linolenic acid than cells from warm-acclimated trout. Cold acclimation resulted in degrees of compensation of desaturation and elongation rates that depended on the fatty acid family and specific reaction in the sequence. In the oleic acid family, reaction rates showed no compensation; partial compensation was observed in the linoleic acid family, and perfect (e.g., Δ6 desaturation) to overcompensation (e.g., Δ4 desaturation) in the linolenic acid family. Cells from cold-acclimated trout had higher rates of production of linolenic-derived acids when assayed at 5 than 20 °C. The proportion of the product of a given desaturation or elongation reaction that continued to the next reaction in the sequence was higher when assayed at 5 than 20 °C, increasing the probability of producing polyunsaturates. The results suggest that the substrate preference of the desaturation and elongation enzymes, the compensation of reaction rates, and the possible “link” between certain reactions in the metabolic sequence may ensure the production of poly-unsaturated fatty acids in cold-adapted trout.

Biotin‐responsive immunoregulatory dysfunction in multiple carboxylase deficiency

AbstractMultiple carboxylase deficiency could be associated with defects of the immunoregulatory system. A boy with documented multiple carboxylase deficiency was found to display a fatty acid and biotin‐responsive impairment of his lymphocyte suppressive activityin vitro. Furthermore, prostaglandin E2 (PGE2), a major product of unsaturated fatty acid elongation required forin vitro activation of the immunoregulatory system, was found to be very low in the patient's monocytes. Finally, PGE2 monocytic production responded well to biotin therapy. PGE2 deficiency could result from the combination of an essential fatty acid deficiency with an impaired elongation of unsaturated fatty acids possibly due to a defect of the biotin‐dependent acetyl‐CoA carboxylase reaction.

Aspects of fatty acid metabolism in Galleria mellonella (L.) (Lepidoptera: Pyralidae): Isolation of the elongation system

1. 1. After short exposure periods to 14C-1-acetate, Galleria mellonella incorporates activity into octadecanoic (steraic) acid, consistent with the elongation synthetic mechanism. No de novo synthesis, involving the incorporation of 14C-1-acetate was detected until a few hours after initial exposure. It appears, therefore, that the two synthetic mechanisms of elongation and de novo synthesis can be studied independently, by varying the exposure periods to 14C-1-acetate. 2. 2. The desaturation reaction yielding 9-octadecenoic acid corresponds with the incorporation of 14C-1-acetate into octadecanoic acid in a typical precursor-product fashion but the rate of incorporation is much slower. 3. 3. No elongation of unsaturated fatty acids with 14C-1-acetate was detected in G. mellonella, in the first 30 minutes of exposure. 4. 4. The incorporation rate of acetate into 9-octodecenoic acid is much lower than that of octadecanoic acid, indicating that the unsaturates may be storage products with lower fractional turnover rates. This is consistent with the percentage composition, in which the unsaturates, particularly 9-octadecenoic acid, comprise the largest pool. This is generally true in all animals and plants. 5. 5. Accurate calculations of fractional turnover rates in vivo are impractical at this time.

Chain Elongation of α- and γ-Linolenic Acids and the Effect of Other Fatty Acids on Their Conversion in Vitro

Abstract The chain elongations of α- and γ-linolenic acids with malonyl coenzyme A with rat liver microsomes were studied. γ-Linolenic acid was converted to eicosatrienoic acid in about 70% yield, whereas α-linolenic acid was only converted to about 30% under the same conditions. Unsaturated acids of the linoleic acid family present in the incubation mixture increased the conversion of both linolenic acids. The conversion of γ-linolenic acid was inhibited most effectively by trienoic acids: 9,12,15-octadecatrienoic, 5,8,11- octadecatrienoic, and 5,8,11-heptadecatrienoic acids. α- Linolenic acid was mainly inhibited by its own metabolic products, eicosapentaenoic and docosahexaenoic acids, when these were added. Saturated fatty acids inhibited the conversion of both acids, but in quite different fashions. The inhibition of α-linolenic acid was independent of the chain length of the saturated acids, whereas γ-linolenic acid was most effectively inhibited by tetradecanoic and pentadecanoic acids. The strong inhibition by the saturated fatty acids of the elongation of unsaturated fatty acids may serve as a regulation of the composition of tissue lipids.