75685-85-7Relevant articles and documents
Biochemical characterization of the PHARC-associated serine hydrolase ABHD12 reveals its preference for very-long-chain lipids
Joshi, Alaumy,Shaikh, Minhaj,Singh, Shubham,Rajendran, Abinaya,Mhetre, Amol,Kamat, Siddhesh S.
, p. 16953 - 16963 (2018/11/21)
Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a rare genetic human neurological disorder caused by null mutations to the Abhd12 gene, which encodes the integral membrane serine hydrolase enzyme ABHD12. Although the role that ABHD12 plays in PHARC is understood, the thorough biochemical characterization of ABHD12 is lacking. Here, we report the facile synthesis of mono-1-(fatty)acyl-glycerol lipids of varying chain lengths and unsaturation and use this lipid substrate library to biochemically characterize recombinant mammalian ABHD12. The substrate profiling study for ABHD12 suggested that this enzyme requires glycosylation for optimal activity and that it has a strong preference for very-long-chain lipid substrates. We further validated this substrate profile against brain membrane lysates generated from WT and ABHD12 knockout mice. Finally, using cellular organelle fractionation and immunofluorescence assays, we show that mammalian ABHD12 is enriched on the endoplasmic reticulum membrane, where most of the very-long-chain fatty acids are biosynthesized in cells. Taken together, our findings provide a biochemical explanation for why very-long-chain lipids (such as lysophosphatidylserine lipids) accumulate in the brains of ABHD12 knockout mice, which is a murine model of PHARC.
Determination of the Absolute Configuration of a Monoglyceride Antibolting Compound and Isolation of Related Compounds from Radish Leaves (Raphanus sativus)
Ogihara, Tsuyoshi,Amano, Naruki,Mitsui, Yuki,Fujino, Kaien,Ohta, Hiroyuki,Takahashi, Kosaku,Matsuura, Hideyuki
supporting information, p. 872 - 878 (2017/05/05)
A monoglyceride (1) has been reported to possess an antibolting effect in radish (Raphanus sativus), but its absolute configuration at the C-2 position was not determined earlier. In this work, the absolute configuration of 1 was determined to be (2S), and it was also accompanied by one new (2) and two known monoglycerides (3 and 4). The chemical structure of 2 was determined as β-(7′Z,10′Z,13′Z)-hexadecatrienoic acid monoglyceride (β-16:3 monoglyceride). Qualitative and quantitative analytical methods for compounds 1-4 were developed, using two deuterium-labeled compounds (8 and 9) as internal standards. The results revealed a broader range of distribution of 1-4 in several annual winter crops. It was also found that these isolated compounds have an inhibitory effect on the root elongation of Arabidopsis thaliana seedlings at concentrations of 25 and 50 μM in the medium. However, the inhibitory effect of 1 was not dependent on coronatin-insensitive 1 (COI1) protein, which may suggest the involvement of an unidentified signaling system other than jasmonic acid signaling.
Influence of fatty acid desaturation on spontaneous acyl migration in 2-monoacylglycerols
Compton, David L.,Laszlo, Joseph A.,Appell, Michael,Vermillion, Karl E.,Evans, Kervin O.
, p. 2259 - 2267 (2013/01/15)
The effect of desaturation from the C9 to the C15 carbon of 2-monoacylglycerol (2-MAG) fatty acids on spontaneous acyl migration is described. Three 2-MAG species, 2-monooleoylglycerol (C18:1 cis-Δ9), 2-monolinoleoylglycerol (C18:2 cis-Δ9,12), and 2-monolinolenoylglycerol (C18:3 cis-Δ9,12,15) were synthesized by lipase-catalyzed ethanolysis of their respective triacylglycerols and isolated in >60 % yield and at 2-MAG purities of >95 % relative to 1-monoacylglycerol (1-MAG). 1H-NMR spectroscopy was used to monitor the spontaneous acyl migration of the 2-MAG species over a temperature range from 20 to 80 °C. The relative energies of activation calculated from the Arrhenius relationships of the 2-MAG acyl migration rate constants were 73.3, 68.0, and 72.9 kJ mol-1 for the three 2-MAG species, respectively. Density functional calculations performed using the B3LYP functional at the 6-31+G* basis set on the three ketal ring intermediate of the three 2-MAG species followed a similar trend with a lack of relative energetic preference associated with the degree of desaturation. The kinetically determined relative activation energies were approximately twofold higher than the theoretical relative Gibbs free energies of the intermediates, suggesting that other factors influence acyl migration. In general, increasing desaturation after the C9 carbon of 2-MAG fatty acids had no appreciable effect on acyl migration rates. AOCS (outside the USA) 2012.
Monoglycerides from the brown alga Sargassum sagamianum: Isolation, synthesis, and biological activity
Chang, Hyeun Wook,Jang, Kyoung Hwa,Lee, Doohyun,Kang, Hee Ryong,Kim, Tae-Yoon,Lee, Bong Ho,Choi, Byoung Wook,Kim, Sanghee,Shin, Jongheon
body text, p. 3589 - 3592 (2009/04/11)
Polyunsaturated fatty acid-derived monoglycerides were characterized from the marine brown alga Sargassum sagamianum, collected from Jeju Island, Korea. A new compound of this structural class was isolated and determined to be 1-octadecatetraenoyl glycerol, by combined spectroscopic methods. Based on the structures and bioactivity of these compounds, a series of monoglycerides were synthesized using glycerol and various fatty acids. Several compounds exhibited moderate to significant inhibition of phospholipase A2 and cyclooxygenase-2.
Practical syntheses of triacylglycerol regioisomers containing long-chain polyunsaturated fatty acids
Fraser, Benjamin H.,Perlmutter, Patrick,Wijesundera, Chakra
, p. 11 - 21 (2008/09/21)
Docosahexaenoic acid (DHA, 22:6n-3) is known to protect against a range of degenerative disease conditions and aid in the development of eye and brain function in infants. In dietary lipids DHA is found primarily in the triacylglycerol (TAG) form. However, the effects of the positional distribution of DHA in TAG on lipid functional properties such as bioactivity and oxidative stability are not clearly understood. Studies on this subject for the most part are limited by a lack of regioisomerically pure TAG model compounds containing DHA or similar long-chain (LC)-polyunsaturated fatty acids (PUFA). This paper reports on the development of a practical procedure, based on chemical and enzymatic reactions, for the syntheses of regioisomerically enriched, symmetrical and unsymmetrical TAG isomers containing two palmitic acid and one of linoleic acid, linolenic acid, or DHA. 1,3-Selective acylation of glycerol with vinyl esters of fatty acids catalyzed by Candida antarctica lipase and direct coupling with fatty acids in the presence of the coupling agents 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 4-dimethylaminopyridine furnished 1,3-dihexadecanoyl-2-docosahexaenoyl glycerol and its unsymmetrical isomer 1,2-dihexadecanoyl-3-docosahexaenoyl glycerol in 99 and 60% yield, respectively. Critical to the success of the unsymmetrical TAG synthesis is the demonstration that PUFA-containing glycerol acetonides can readily survive appropriately tailored acid-catalyzed conditions. In this way, sufficient quantities of highly regioisomerically enriched PUFA-containing unsymmetrical monoacylglycerols (MAG) and TAG have now become routinely accessible. The methods are amenable to scale-up and could be adopted for regioenriched synthesis of a wide range of TAG. AOCS 2007.
Lipase-catalyzed transesterification of trilinolein or trilinolenin with selected phenolic acids
Sabally, Kebba,Karboune, Salwa,St-Louis, Richard,Kermasha, Selim
, p. 101 - 107 (2007/10/03)
The enzymatic transesterification of selected phenolic acids with TAG, including trilinolein (TLA) and trilinolenin (TLNA), was investigated in an organic solvent medium. Maximal bioconversion of 66% was obtained with a dihydrocaffeic acid (DHCA) to TLA ratio of 1:2 after 5 d of reaction. Similarly, the highest bioconversion of 62% was obtained with a DHCA to TLNA ratio of 1:2, but after 12 d of reaction. However, a ratio of 1:4 DHCA/TLA decreased the bioconversion to 53%. Transesterification reactions of ferulic acid with both TAG, using a ratio of 1:2, resulted in low bioconversion of 16 and 14% with TLA and TLNA, respectively. The overall results indicated that bioconversion of phenolic MAG was higher than that of phenolic DAG. The structures of mono- and dilinoleyl dihydrocaffeate as well as those of mono- and dilinolenyl dihydrocaffeate were confirmed by LC-MS analyses. The phenolic lipids demonstrated moderate radical-scavenging activity. Copyright
Biologically active lipids binding membrane receptors
-
, (2008/06/13)
Neutral lipids are provided characterized by binding to phorboid and ingenoid receptors. These lipids are found in a wide variety of cellular sources as well as milk and may be isolated by specific extraction and chromatographic procedures. Depending upon the source, the glycerides may be mono- or di-glycerides, wherein the total number of carbon atoms of the fatty acids is in the range of 18 to 26, so that the monoglyceride has a fatty acid of at least 18 carbon atoms, while the di-glyceride has a fatty acid of at least 14 carbon atoms.
γ-Aminobutyric acid esters. 2. Synthesis, brain uptake, and pharmacological properties of lipid esters of γ-aminobutyric acid
Jacob,Shashoua,Campbell,Baldessarini
, p. 106 - 110 (2007/10/02)
Two lipid esters of U-14C-labeled and unlabeled γ-aminobutyric acid (GABA) were synthesized to test the possibility that natural lipid analogues, which resemble normal components of lipid bilayer membranes, can penetrate the blood-brain barrier and transport exogenous GABA to the brain. The uptake of 1-linolenoyl-2,3-bis(4-aminobutyryl)propane-1,2,3-triol and 1,2-dilinolenoyl-3-(4-aminobutyryl)propane-1,2,3-triol into mouse brain relative to liver was found to be, respectively, 75- and 127-fold greater than that of free GABA. The results indicate that there is little or no blood-brain barrier for the GABA ester molecules at doses up to 0.36 mmol/kg. Both ester compounds, but neither free GABA nor the lipid components delivered systemically, demonstrated central nervous system depressant properties by inhibiting the general motor activity of mice. Brain tissue has esterase activity which can release GABA from these compounds. This suggests that these compounds function as 'prodrugs' to release GABA in the CNS.
