An acidic morpholine derivative containing glyceride from thraustochytrid, Aurantiochytrium

A novel acidic morpholine-derivative containing glyceride (M-glyceride) was isolated from the cells of two strains of the thraustochytrid, Aurantiochytrium. The glyceride accounted for approximately 0.1 -0.4% of the lyophilized cells. The glyceride consisted of peaks I (85%) and II (15%). The structures of the intact and acetylated glycerides were elucidated by liquid chromatography-quadrupole time-of-flight chromatograph mass spectrometer (LC–Q/TOF) and NMR spectroscopy. The hydrate type of M-glyceride was detected as a minor component by LC–MS/MS. By 2D-NMR experiments, peaks I of the intact M-glyceride were elucidated as 1,2-didocosapentaenoyl-glyceryl-2′-oxy-3′-oxomorpholino propionic acid, and peak II was estimated 1,2-palmitoyldocosapentaenoyl- and/or 1,2-docosapentaenoylpalmitoyl-glyceryl-2′-oxy-3′-oxomorpholino propionic acid. The double bond position of docosapentaenoic acid was of the ω − 6 type (C22 = 5.ω − 6). The M-glyceride content varied by the cell cycle. The content was 0.4% of lyophilized cells at the mid logarithmic phase, and decreased to 0.1% at the mid stationary phase. When cells were grown in 1.0 µM M-glyceride-containing growth media, cell growth was stimulated to 110% of the control. With 0.1 µM acetyl M-glyceride, stimulation of 113% of the control was observed. Finding morpholine derivatives in biological components is rare, and 2-hydroxy-3-oxomorpholino propionic acid (auranic acid) is a novel morpholine derivative.

Understanding the Mechanism and Selectivities of the Reaction of Meta-Chloroperbenzoic Acid and Dibromocarbene with β-Himachalene: A DFT Study

This study was performed to understand the site selectivity in the reaction between β-himachalene and meta-chloroperbenzoic acid (m-CPBA) in the first step followed by the addition of dibromocarbene (CBr2) to the main monoepoxidation product Pα formed in the first reaction. Calculations were performed using the Becke three-parameter hybrid exchange functional and the Lee–Yang–Parr correlation functional (B3LYP) with the 6-311 + G (d, p) basis set. Transition states were located by QST2, and their highlighting was validated by the existence of only one imaginary frequency in the Hessian matrix. The action of m-CPBA on β-himachalene was analyzed on the two double bonds of β-himachalene whose theoretical calculations show that the attack affects the most substituted double bond on α side containing hydrogen of ring junction. The obtained Pα product thereafter treated with dibromocarbene leads via an exothermic reaction to the six-membered ring double bond position of α-monoepoxide. The major products Pαα are kinetically and thermodynamically favored with a high stereoselectivity in perfect correlation with the experimental observations.

The inhibitory activity of glycine transporter 2 targeting bioactive lipid analgesics are influenced by formation of a deep lipid cavity

The human glycine transporter 2 (GlyT2 or SLC6A5) has emerged as a promising drug target for the development of new analgesics to manage chronic pain. N-acyl amino acids inhibit GlyT2 through binding to an allosteric binding site to produce analgesia in vivo with minimal overt side effects. In this paper we use a combination of medicinal chemistry, electrophysiology, and computational modelling to explore the molecular basis of GlyT2 inhibition at the allosteric site. We show how N-acyl amino acid head group stereochemistry, tail length and double bond position promote enhanced inhibition by deep penetration into the binding pocket. This work provides new insights into the interaction of lipids with transport proteins and will aid in future rational design of novel GlyT2 inhibitors.

Metabolic plasticity in cancer activates apocryphal pathways for lipid desaturation

Fatty acid (FA) modifications, such as enzymatic desaturation and elongation, have long been thought to involve sequential and highly specific enzyme-substrate interactions, which result in canonical products that are well-defined in their chain lengths, degree of unsaturation and double bond positions.1 These products act as a supply of building blocks for the synthesis of complex lipids supporting a symphony of lipid signals and membrane macrostructure. Recently, it was brought to light that differences in substrate availability due to enzyme inhibition can activate alternative pathways in a range of cancers, potentially altering the total species repertoire of FA metabolism.2,3 We have used isomer-resolved lipidomics to analyse human prostate tumours and cancer cell lines and reveal, for the first-time, the full extent of metabolic plasticity in cancer. Assigning the double bond position(s) in simple and complex lipids allows mapping of fatty acid desaturation and elongation via hitherto apocryphal metabolic pathways that generate FAs with unusual sites of unsaturation. Downstream utilisation of these FAs is demonstrated by their incorporation into complex structural lipids. The unsaturation profiles of different phospholipids reveal substantive structural variation between classes that will, necessarily, modulate lipid-centred biological processes in cancer cells including membrane fluidity3-5 and signal transduction.6-8

A method to determine the double bond position in unsaturated fatty acids by solvent plasmatization using liquid chromatography-mass spectrometry

Fatty acids (FAs) are the central components of life: they constitute biological membranes in the form of lipid, act as signaling molecules, and are used as energy sources. FAs are classified according to their chain lengths and the number and position of carbon-carbon double bond, and their physiological character is largely defined by these structural properties. Determination of the precise structural properties is crucial for characterizing FAs, but pinpointing the exact position of carbon-carbon double bond in FA molecules is challenging. Herein, a new analytical method is reported for determining the double bond position of mono- and poly-unsaturated FAs using liquid chromatography-mass spectrometry (LC-MS) coupled with solvent plasmatization. With the aid of plasma on ESI capirally, epoxidation or peroxidation of carbon-carbon double bond in FAs is facilitated. Subsequently, molecular fragmentation occurs at or beside the epoxidized or peroxidized double bond via collision-induced dissociation (CID), and the position of the double bond is elucidated. In this method, FAs are separated by LC, modified by plasma, fragmented via CID, and detected using a time-of-flight mass spectrometer in a seamless manner such that the FA composition in a mixture can be determined. Our method enables thorough characterization of FA species with distinguishing multiple isomers, and therefore can uncover the true diversity of FAs for their application in food, health, and medical sciences.

Characterization and Antioxidant Activity of Essential Oil of Four Sympatric Orchid Species

The volatile fractions from fresh inflorescences of naturally growing orchids Anacamptis coriophora (L.) R. M. Bateman, Pridgeon & M. W. Chase subsp. fragrans (Pollini), Anacamptis pyramidalis (L.) R. Ophrys holosericea (Burm.) Greuter and Serapias vomeracea (Burm. f.) B. were isolated by steam distillation and analyzed by GC/FID and GC/MS. Saturated hydrocarbons were quantified as the major constituents of the volatile fraction (47.87–81.57% of the total essential oil), of which long-chain monounsaturated hydrocarbons accounted from 9.20% to 32.04% of the total essential oil. Double bond position in linear alkenes was highlighted by dimethyl disulfide derivatization and MS fragmentation. Aldehydes (from 3.45 to 18.18% of the total essential oil), alcohols (from 0.19% to 13.48%), terpenes (from 0.98 to 2.50%) and acids (0.30 to 2.57%) were also detected. These volatiles compounds may represent a particular feature of these plant species, playing a critical role in the interaction with pollinators. DPPH assay evaluating the antioxidant activity of the essential oils was carried out, showing a dose-dependent antioxidant activity.