56630-71-8Relevant 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.
Preparation of diacid 1,3-diacylglycerols
Craven, R. John,Lencki, Robert W.
experimental part, p. 1281 - 1291 (2011/08/21)
A complete methodology (including synthesis, purification and analysis) for the preparation of 1,3-DAG is described. For a successful synthesis project, the strengths and weaknesses of each particular process should be taken into account and measures taken to offset or balance potential weaknesses. To this end, we describe some of the challenges associated with: chemically and enzymatically catalyzed acylglycerol syntheses; recrystallization and flash chromatography for purification of partial acylglycerols; and thin-layer chromatography (TLC) separation of DAG. For this work, 1-MAG intermediates and subsequent diacid 1,3-DAG were prepared using non-enzymatic methods, whereas, monoacid 1,3-DAG were prepared by enzymatic methods. It was not always possible to obtain pure samples of target compounds-in recrystallizations this is due to solid solution formation and co-crystallization and in chromatographic separations it is due to co-elution of components with similar Rf. Furthermore, TLC Rf of DAG is determined by two main factors: acyl chain length and positional isomerism. Interestingly, while the role of positional isomerism is well-known, the role of acyl chain length in these separations has only recently come to light.
Study of the effect of DATEM. 1. Influence of fatty acid chain length on rheology and baking
Koehler, Peter,Grosch, Werner
, p. 1863 - 1869 (2007/10/03)
To answer the question of which fatty acid residue is the most effective, diacetyltartaric esters of monoglycerides (DATEMs) with fatty acids of chain lengths 6:0-20:0 were synthesized. The activity of synthesized DATEMs and commercial DATEM products was studied by means of rheological methods and a microscale baking test with 10 g of flour. Variation of the acyl residue from 6:0 to 22:0 showed that stearic acid (18:0) had the best effect on the baking activity of DATEM (loaf volume increased by 62%). DATEMs containing unsaturated fatty acids (18:1, 18:2) or DATEMs produced from diacylglycerols instead of monoacylglycerols showed a slight increase of the loaf volumes. A slight effect of DATEM on the rheology of dough was observed. However, much greater was the effect on the gluten isolated from doughs prepared with DATEM. The resistance of gluten to extension was increased after the addition of increasing amounts of DATEM (0.1-0.5%). Within the series of DATEMs derived from the homologous series of monoacylglycerols the product based on glycerol monostearate (18:0) showed a maximum increase of the gluten resistance.
