Long-Chain and Medium-Chain Fatty Acids in Energy Metabolism of Murine Kidney Mitochondria

Scientists have long established that fatty acids are the primary substrates for kidney mitochondria. However, to date we still do not know how long-chain and middle-chain fatty acids are oxidized at the mitochondrial level. Our previous research has shown that mitochondria from the heart, brain, and kidney oxidize palmitoylcarnitine at a high rate only in the presence of succinate, glutamate, or pyruvate. In this paper, we report properties of the isolated kidney mitochondria and how malate and succinate affect the oxidation of C16 and C8 acylcarnitines. The isolated kidney mitochondria contain very few endogenous substrates and require malate to oxidize pyruvate, glutamate, and C16 or C8 acylcarnitines. We discovered that with 10 µM of C16 or C8 acylcarnitines, low concentrations of malate (0.2 mM) or succinate (0.5 mM) enhance the States 4 and 3 respiratory rates several times. The highest respiration rates were observed with C16 or C8 acylcarnitines and 5 mM succinate mixtures. Results show that kidney mitochondria, unlike the heart and brain mitochondria, lack the intrinsic inhibition of succinate dehydrogenase. Additionally, results show that the oxidation of fatty acid by the small respirasome’s supercomplex generates a high level of CoQH2, and this makes SDH in the presence of succinate reverse the flow of electrons from CoQH2 to reduce fumarate to succinate. Finally, we report evidence that succinate dehydrogenase is a key mitochondrial enzyme that allows fast oxidation of fatty acids and turns the TCA cycle function from the catabolic to the anabolic and anaplerotic metabolic pathways.     

Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain,Heart, and Kidney Mitochondria

We present evidence that metabolic syndrome (MetS) represents the postreproductive stage of the human postembryonic ontogenesis. Accordingly, the genes governing this stage experience relatively weak evolutionary selection pressure, thus representing the metabolic phenotype of distant ancestors with β-oxidation of long-chain fatty acids (FAs) as the primary energy source. Mitochondria oxidize at high-rate FAs only when succinate, glutamate, or pyruvate are present. The heart and brain mitochondria work at a wide range of functional loads and possess an intrinsic inhibition of complex II to prevent oxidative stress at periods of low functional activity. Kidney mitochondria constantly work at a high rate and lack inhibition of complex II. We suggest that in people with MetS, oxidative stress is the central mechanism of the heart and brain pathologies. Oxidative stress is a secondary pathogenetic mechanism in the kidney, while the primary mechanisms are kidney hypoxia caused by persistent hyperglycemia and hypertension. Current evidence suggests that most of the nongenetic pathologies associated with MetS originate from the inconsistencies between the metabolic phenotype acquired after the transition to the postreproductive stage and excessive consumption of food rich in carbohydrates and a sedentary lifestyle.     

Heat Treatment and Chemical Composition of Fatty Acids and Rosin Acids Mixtures: Effects on Their Thermal Properties and Morphology

Mixtures of fatty acids and rosin acids are industrially important products utilized as a raw material for several purposes. Their thermal properties, especially cold stability and crystallization behavior is also important. Several fatty acid and rosin acid mixtures both from industrial products and from commercially available fatty and rosin acids were prepared and treated for 30 min at 80 °C under an inert atmosphere. Thereafter, the mixture was cooled to the desired temperature. Determination of the cloud point, chemical analysis of liquid and solid phase, thermal analysis by differential scanning calorimetry as well as morphology analysis by scanning electron microscopy were performed. The results revealed that crystallization was more rapid when it occurred at 10 °C compared to 25 °C. The crystal sizes increased with decreasing the crystallization temperature. Furthermore, crystals were of irregular shape and agglomerated when rapid cooling of the mixture occurred. Chemical analysis revealed that liquid phase was enriched with stearic acid, whereas crystals contained large amounts of abietic, dehydroabietic and linoleic acids. The cloud point of the mixtures increased with increasing amount of stearic and rosin acids. Dehydroabietic acid addition improved the cold stability of the synthetic fatty acid–rosin acids mixture.     

Importance of the Atmosphere on the Mechanisms and Kinetics of Reactions Between Silica and Solid Sodium Carbonate

Using thermogravimetric analysis, the reaction kinetics between powders of silica (SiO₂) and sodium carbonate (Na₂CO₃) are investigated below the melting point of sodium carbonate, under different atmospheres. These experiments show that the reaction kinetics critically depend on the partial pressure of CO₂ in the surrounding atmosphere. Under a flow of nitrogen, the reaction rate is constant with time and follows an Arrhenian law, with a weak influence of the grain sizes of the two reactants. Under a flow of carbon dioxide, the reaction rate is found to be much slower, to have nonlinear time dependence and to have a weaker temperature dependence. The influence of grain size is also found to be more significant in this case. Two different reaction mechanisms between silica and sodium carbonate may account for these results: (i) sodium carbonate dissociates at a rate depending on the partial pressure of CO₂, releasing sodium to the vapor, that may then react with the surface of silica grains, or (ii) silica and sodium carbonate grains react at granular contacts between individual grains. A quantitative equation is proposed that accounts for the influence of temperature, , and grain size on the reaction rate between silica and sodium carbonate.     

Curupira tefeensis (Olacaceae) — A Rich Source of Very Long Chain Fatty Acids

The fatty acid composition of the seed oil of Curupira tefeensis was analysed by capillary GC of their methyl esters. The gaschromatographic assignments were ensured by corresponding mass spectra. The oil is composed to more than 62% of very long chain fatty acids (>C18). Erucic acid is found to be the main component (35%). The position of the double bonds of the monounsaturated fatty acids (MUFAME) was verified after derivatization with dimethyl disulfide and subsequent GC/MS analysis. All identified MUFAME belong to the (n-9-)type. The UV-spectroscopical data show that approx. 1.2% conjugated acetylenic fatty acids occur in the oil. Furthermore IR- and NMR-spectroscopical investigations and the basic analyses of the seed were carried out.     

Fibroblast Growth Factor-21 and the Beneficial Effects of Long-Chain n-3 Polyunsaturated Fatty Acids

Long‐chain n‐3 polyunsaturated fatty acids (LC n‐3 PUFA) in the diet protect against insulin resistance and obesity. Fibroblast growth factor‐21 (Fgf21) is a hormonal factor released mainly by the liver that has powerful anti‐diabetic effects. Here, we tested whether the beneficial metabolic effects of LC n‐3 PUFA involve the induction of Fgf21. C57BL/6 J mice were exposed to an obesogenic, corn‐oil‐based, high‐fat diet (cHF), or a diet in which corn oil was replaced with a fish‐derived LC n‐3 PUFA concentrate (cHF + F) using two experimental settings: short‐term (3 weeks) and long‐term treatment (8 weeks). CHF + F reduced body weight gain, insulinemia, and triglyceridemia compared to cHF. cHF increased plasma Fgf21 levels and hepatic Fgf21 gene expression compared with controls, but these effects were less pronounced or absent in cHF + F‐fed mice. In contrast, hepatic expression of peroxisome proliferator‐activated receptor (PPAR)‐α target genes were more strongly induced by cHF + F than cHF, especially in the short‐term treatment setting. The expression of genes encoding Fgf21, its receptors, and Fgf21 targets was unaltered by short‐term LC n‐3 PUFA treatment, with the exception of Ucp1 (uncoupling protein 1) and adiponectin genes, which were specifically up‐regulated in white fat. In the long‐term treatment setting, the expression of Fgf21 target genes and receptors was not differentially affected by LC n‐3 PUFA. Collectively, our findings indicate that increased Fgf21 levels do not appear to be a major mechanism through which LC n‐3 PUFA ameliorates high‐fat‐diet‐associated metabolic disorders.     

Kinetics and reactors — The engineer's dilemma

Scaleup of catalytic reactors is often unrewarding because of the incompatibility of chemical and physical similarity requirements. Hence, a rational design procedure usually requires experimental study of global rates of reaction, as well as kinetics of the chemical steps at a catalyst site. This paper examines the role of laboratory and pilot-plant reactor data in the design procedure. Recent developments in laboratory reactors, and the potential for ultimately eliminating the need for global rate measurements, are considered.     

Kinetics of growth on aqueous — oil and aqueous — solid dispersed systems

Dispersed phase continuous culture systems are very complicated. Indeed, they can differ considerably in their behaviour from the usual homogeneous continuous culture systems. Experimental studies on cell adsorption—desorption rates under various conditions of surfactant concentrations and droplet coalescence and break-up is needed in order to understand fully the mechanism of substrate utilisation in these continuous systems.     

Mono‐Estolide Synthesis from trans‐8‐Hydroxy‐Fatty Acids by Lipases in Solvent‐Free Media and Their Physical Properties

Pseudomonas aeruginosa 42A2 is known to produce two hydroxy‐fatty acids, 10(S)‐hydroxy‐8(E)‐octadecenoic and 7,10(S,S)‐dihydroxy‐8(E)‐octadecenoic acids, when cultivated in a mineral medium using oleic acid as a single carbon source. These compounds were purified, 91 and 96 % respectively, to produce two new families of estolides: trans‐8‐estolides and saturated estolides from the monohydroxylated monomer. trans‐8‐estolides were produced by three different lipases (Novozym 435, Lipozyme RM IM and Lipozyme TL IM) with reaction yields between 68.4 ± 2.1 and 94.7 ± 2.4 % in a solvent‐free medium at 80 °C in 168 h under vacuum. Novozym 435 was found to be the most efficient biocatalyst for both hydroxy‐fatty acids with reaction yields of 71.7 ± 2.3 and 94.7 ± 2.4 %, respectively. Moreover, saturated estolides were also produced from a saturated 10(S)‐hydroxy‐8(E)‐octadecenoic. These estolides were chemically and enzymatically synthesized with Novozym 435, under the previous described reaction conditions with yields of 60.7 ± 2.1 and 71.2 ± 2.3 % respectively. Finally, viscosity, glass transition temperature, decomposition temperatures and enthalpies were determined to characterize both types of estolides. Thermal applications for both types of polyesters were improved since glass transition temperatures were lowered and decomposition temperatures were increased, with respect to their corresponding substrates.     

Structural Elucidation of Long-Chain Fatty Acids and Alcohols by Mass Spectrometry of their Cyclic Amide Derivatives

Several deuterium-labelled normal-chain carboxylic acids and alcohols, their unlabelled analogues and several unlabelled methyl-branched chain fatty acids and alcohols have been investigated by mass spectrometry — at different electron energies — of their respective N-acyl 2-methylaziridine and pyrrolidine and N-alkyl 2-pyrrolidone and 2-piperidone derivatives. The result shows that these kinds of amides and lactams are among the best derivatives of fatty acids and alcohols for structural elucidation by mass spectrometry.     

The Impact of a Ketogenic Diet and Liver Dysfunction on Serum Very Long-Chain Fatty Acids Levels

Peroxisomes play an essential role in mammalian cellular metabolism, particularly in oxidation fatty acid pathways. Serum very long-chain fatty acids (VLCFA), the main biochemical diagnostic parameters for peroxisomal disorders, were examined in 25 neurological patients with epilepsy on a ketogenic diet and 27 patients with liver dysfunction. The data show that patients on a ketogenic diet have increased levels of C22:0 and C24:0, but not C26:0, and normal C24:0/C22:0 and C26:0/C22:0. Patients with liver insufficiency showed a slightly elevated level of C26:0, a normal level of C24:0 and a decreased level of C22:0; thus in 21/27 the ratio of C24:0/C22:0 was increased and 15/27 the ratio of C26:0/C22:0 was increased.     

Sources and Bioactive Properties of Conjugated Dietary Fatty Acids

The group of conjugated fatty acids known as conjugated linoleic acid (CLA) isomers have been extensively studied with regard to their bioactive potential in treating some of the most prominent human health malignancies. However, CLA isomers are not the only group of potentially bioactive conjugated fatty acids currently undergoing study. In this regard, isomers of conjugated α‐linolenic acid, conjugated nonadecadienoic acid and conjugated eicosapentaenoic acid, to name but a few, have undergone experimental assessment. These studies have indicated many of these conjugated fatty acid isomers commonly possess anti‐carcinogenic, anti‐adipogenic, anti‐inflammatory and immune modulating properties, a number of which will be discussed in this review. The mechanisms through which these bioactivities are mediated have not yet been fully elucidated. However, existing evidence indicates that these fatty acids may play a role in modulating the expression of several oncogenes, cell cycle regulators, and genes associated with energy metabolism. Despite such bioactive potential, interest in these conjugated fatty acids has remained low relative to the CLA isomers. This may be partly attributed to the relatively recent emergence of these fatty acids as bioactives, but also due to a lack of awareness regarding sources from which they can be produced. In this review, we will also highlight the common sources of these conjugated fatty acids, including plants, algae, microbes and chemosynthesis.     

Long-Chain Omega-3 Polyunsaturated Fatty Acids in the Blood of Children and Adolescents with Juvenile Bipolar Disorder

Reduced long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been reported in adult patients suffering from depression and bipolar disorder (BD). LCn-3PUFA status has not previously been examined in children and adolescents with BD compared with healthy controls. Fifteen children and adolescents (9-18 years, M +/- SD = 14.4 +/- 3.48) diagnosed with juvenile bipolar disorder (JBD) and fifteen healthy age and sex-matched controls were assessed for dietary intake and fasting red blood cell (RBC) membrane concentrations of LCn-3PUFA. Fatty acid concentrations were compared between participants diagnosed with JBD and controls after controlling for dietary intake. RBC membrane concentrations of EPA and DHA were not significantly lower in participants diagnosed with JBD compared with healthy controls (M +/- sem EPA = 3.37 +/- 0.26 vs. 3.69 +/- 0.27 microg/mL, P = 0.458; M +/- sem DHA = 22.08 +/- 2.23 vs. 24.61 +/- 2.38 microg/mL, P = 0.528) after controlling for intake. Red blood cell DHA was negatively (r = -0.55; P = 0.044) related to clinician ratings of depression. Although lower RBC concentrations of LCn-3PUFA were explained by lower intakes in the current study, previous evidence has linked reduced LCn-3PUFA to the aetiology of BD. As RBC DHA was also negatively related to symptoms of depression, a randomised placebo-controlled study examining supplementation with LCn-3PUFA as an adjunct to standard pharmacotherapy appears warranted in this patient population.     

Microbial Synthesis of Medium‐Chain α,ω‐Dicarboxylic Acids and ω‐Aminocarboxylic Acids from Renewable Long‐Chain Fatty Acids

Biotransformation of long‐chain fatty acids into medium‐chain α,ω‐dicarboxylic acids or ω‐aminocarboxylic acids could be achieved with biocatalysts. This study presents the production of α,ω‐dicarboxylic acids (e.g., C₉, C₁₁, C₁₂, C₁₃) and ω‐aminocarboxylic acids (e.g., C₁₁, C₁₂, C₁₃) directly from fatty acids (e.g., oleic acid, ricinoleic acid, lesquerolic acid) using recombinant Escherichia coli‐based biocatalysts. ω‐Hydroxycarboxylic acids, which were produced from oxidative cleavage of fatty acids via enzymatic reactions involving a fatty acid double bond hydratase, an alcohol dehydrogenase, a Baeyer–Villiger monooxygenase and an esterase, were then oxidized to α,ω‐dicarboxylic acids by alcohol dehydrogenase (ADH, AlkJ) from Pseudomonas putida GPo1 or converted into ω‐aminocarboxylic acids by a serial combination of ADH from P. putida GPo1 and an ω‐transaminase of Silicibacter pomeroyi. The double bonds present in the fatty acids such as ricinoleic acid and lesquerolic acid were reduced by E. coli‐native enzymes during the biotransformations. This study demonstrates that the industrially relevant building blocks (C₉ to C₁₃ saturated α,ω‐dicarboxylic acids and ω‐aminocarboxylic acids) can be produced from renewable fatty acids using biocatalysis.

     

Low-Temperature Crystallization for Separating Monoacetylated Long-Chain Sophorolipids: Characterization of Their Surface-Active and Antimicrobial Properties

Pseudohyphozyma (formerly Rhodotorula) bogoriensis synthesizes long-chain-length (22-carbon chain) sophorolipids (22:0-SL) that are variously acetylated at the 6′- or/and 6″-carbons of the sophorose unit. In this paper, we describe a low-temperature crystallization protocol that preferentially separates the 6′-monoacetylated 22:0-SL (6′-Ac₁-22:0-SL) from a parental mixture of 22:0-SL containing a majority (64.7%) of the 6′,6″-diacetylated moiety (6′,6″-Ac₂-22:0-SL), as deduced from high-pressure-liquid-chromatography evaporative-light-scattering-detection (HPLC-ELSD) and LC/Q-TOF-MS analyses. Tensiometry measurements using the Wilhelmy plate method yielded minimum-surface-tension (SFT_min) and critical-micelle-concentration (CMC) values of 34.6 ± 1.0 mN m⁻¹ and 0.014 mM, respectively, for 6′-Ac₁-22:0-SL (CRYSTAL) fraction and 34.9 ± 1.0 mM m⁻¹ (SFT_min) and 0.018 (CMC) for the hexane precipitate (Hx-PRCP) fraction containing a high concentration (89.2%) of the diacetylated 6′,6″-Ac₂-22:0-SL after crystal removal. In contrast, the SFT_min and CMC of the well-studied 16-18 carbon (C_16-18)-SL of Starmerella bombicola were 35–37.2 mN m⁻¹ and 0.05-(>0.3) mM, respectively. Individually, the purified CRYSTAL and Hx-PRCP fractions exhibited a similar degree of strong growth-inhibition activity against Cutibacterium (formerly Propionibacterium) acnes as determined by an agar-plate zone of inhibition assay. Study on the growth inhibition of oral health-related bacteria, i.e., Streptococcus mutans and Lactobacillus acidophilus, showed that, depending on the bacteria and strains tested, the CRYSTAL fraction was either slightly better than or equally effective as the Hx-PRCP fraction in inhibiting cell growth.     

Abutilon indicum Seed Oil — Characterisation of HBr-Reactive Acids

The seed oil of Abutilon indicum (Malvaceae) contains three HBr-reactive fatty acids. These are shown to be cis-12,13-epoxyoleic (vernolic) acid, 1.6% 9,10-methylene-octadec-9-enoic (sterculic) acid, 0.9%; as well as 8,9-methylene-heptadec-8-enoic (malvalic) acid, 2.3%. Quantitative results are obtained by combining informations about the HBr-titration, the preparative thin layer separation of oxygenated and non-oxygenated acids, and gas liquid chromatographic analysis.     

Structures and Mechanisms of a Novel Bacterial Transport System for Fatty Acids

Bacterial acquisition of metabolites is largely facilitated by transporters with unique substrate scopes. The tripartite ATP-independent periplasmic (TRAP) transporters comprise a large family of bacterial proteins that facilitate the uptake of a variety of small molecules. It has been reported that some TRAP systems encode a fourth protein, the T component. The T-component, or TatT, is predicted to be a periplasmic-facing lipoprotein that enables the uptake of metabolites from the outer membrane. However, no substrates were revealed for any TatT and their functional role(s) remained enigmatic. We recently identified a homolog in Methylococcus capsulatus that binds to sterols, and herein, we report two additional homologs that demonstrate a preference for long-chain fatty acids. Our bioinformatics, quantitative analyses of protein-ligand interactions, and high-resolution crystal structures suggest that TatTs might facilitate the trafficking of hydrophobic or lipophilic substrates and represent a new class of bacterial lipid and fatty acid transporters.     

论加强有机反应类型和机理学习的教学方法

有机化学作为化学的四大子学科之一,是一门研究有机化合物结构、性质、应用及其相互转化所遵循的理论和规律的一门科学。其特点是化合物数目庞大,反应众多,机理复杂。为了加强有机化学反应类型和机理的学习,本文提出了Seminar、小测验、人名反应、网络和移动平台、化学史的学习方法以及学生自主授课法,旨在通过丰富多彩的教学方法,充分调动学生学习的积极性,提高学生的学习兴趣并能主动参与到课堂教与学的活动中来。