Acetyl-DL-propargylglycine ethyl ester

The need to understand and control ester synthesis is driven by the fact that esters play a key role in the sensorial quality of fermented alcoholic beverages like beer, wine and sake. As esters are synthesized in yeast via several complex metabolic pathways, there is a need to gain a clear understanding of ester metabolism and its regulation. The individual genes involved, their functions and regulatory mechanisms have to be identified. In alcoholic beverages, there are two important groups of esters: the acetate esters and the medium-chain fatty acid (MCFA) ethyl esters. For acetate ester synthesis, the genes involved have already been cloned and characterized. Also the biochemical pathways and the regulation of acetate ester synthesis are well defined. With respect to the molecular basis of MCFA ethyl ester synthesis, however, significant progress has only recently been made. Next to the characterization of the biochemical pathways and regulation of ester synthesis, a new and more important question arises: what is the advantage for yeast to produce these esters? Several hypotheses have been proposed in the past, but none was satisfactorily. This paper reviews the current hypotheses of ester synthesis in yeast in relation to the complex regulation of the alcohol acetyl transferases and the different factors that allow ester formation to be controlled during fermentation.

There is currently growing attention being paid to the role of elevated triglycerides (TGs) as important mediators of residual atherosclerotic cardiovascular disease (ASCVD) risk. This role is supported by genetic studies and by the persistent residual risk of ASCVD, even after intensive statin therapy. Although TG lowering drugs have shown conflicting results when tested in cardiovascular outcome trials, data from the REDUCE-IT study with the ethyl ester of ω-3 eicosapentaenoic acid (EPA) have revived hope in this area of research. The aim of the present review is to critically discuss the most recent large trials with ω-3 fatty acids (FAs) trying to elucidate mechanistic and trial-related differences, as in the case of REDUCE-IT and STRENGTH studies. The ω-3 FAs may lower cardiovascular risk through a number of pleiotropic mechanisms, e.g., by lowering blood pressure, by mediating antithrombotic effects, by providing precursors for the synthesis of specialized proresolving mediators that can inhibit inflammation or by modulating the lipid rafts enriched in cholesterol and sphingolipids. In conclusion, in a field fraught with uncertainties, the ω-3 FAs and especially high dose icosapent ethyl (the ethyl ester of EPA) are at present a most valuable therapeutic option to reduce the ASCVD risk.

Antimicrobial-lock therapy is an economically viable strategy to prevent/reduce the catheter-related bloodstream infections (CRBSI) that are associated with central venous catheters (CVCs). Herein, we report the synthesis and characterization of the S-nitroso-N-acetyl-l-cysteine ethyl ester (SNACET), a nitric oxide (NO)-releasing molecule, and for the first time its application as a catheter lock solution to combat issues of bacterial infection associated with indwelling catheters. Nitric oxide is an endogenous gasotransmitter that exhibits a wide range of biological properties, including broad-spectrum antimicrobial activity. The storage stability of the SNACET and the NO release behavior of the prepared lock solution were analyzed. SNACET lock solutions with varying concentrations exhibited tuneable NO release at physiological levels for >18 h, as measured using chemiluminescence. The SNACET lock solutions were examined for their efficacy in reducing microbial adhesion after 18 h of exposure toStaphylococcus aureus (Gram-positive bacteria) andEscherichia coli (Gram-negative bacteria). SNACET lock solutions with 50 and 75 mM concentrations were found to reduce >99% (ca. 3-log) of the adhered S. aureus and E. coli adhesion to the catheter surface after 18 h. The SNACET lock solutions were evaluated in a more challenging in vitro model to evaluate the efficacy against an established microbial infection on catheter surfaces using the same bacteria strains. A >90% reduction in viable bacteria on the catheter surfaces was observed after instilling the 75 mM SNACET lock solution within the lumen of the infected catheter for only 2 h. These findings propound that SNACET lock solution is a promising biocidal agent and demonstrate the initiation of a new platform technology for NO-releasing lock solution therapy for the inhibition and treatment of catheter-related infections.