Acetyl-CoA carboxylase (ACC) is a key enzyme of fatty acid metabolism with multiple isozymes often expressed in different eukaryotic cellular compartments. ACC-made malonyl-CoA serves as a precursor for fatty acids; it also regulates fatty acid oxidation and feeding behavior in animals. ACC provides an important target for new drugs to treat human diseases. We have developed an inexpensive nonradioactive high-throughput screening system to identify new ACC inhibitors. The screen uses yeast gene-replacement strains depending for growth on cloned human ACC1 and ACC2. In "proof of concept" experiments, growth of such strains was inhibited by compounds known to target human ACCs. The screen is sensitive and robust. Medium-size chemical libraries yielded new specific inhibitors of human ACC2. The target of the best of these inhibitors was confirmed with in vitro enzymatic assays. This compound is a new drug chemotype inhibiting human ACC2 with 2.8 μM IC 50 and having no effect on human ACC1 at 100 μM.fatty acid metabolism | human health

A TiO 2 -coated rotating corrugated reactor is experimentally characterized and simulated for ultraviolet (UV)-based photo degradation of methylene blue (MB). Using degradation kinetics derived from flat-plate experiments and finiteelement discrete-ordinate models simulating spatially and temporally varying radiation patterns from a UV-lamp array, the simulated reactor performance is experimentally validated and extended to explore the impact of geometry variations. Mass-transfer limitations between the corrugated surface and the reservoir bulk are identified as a determining factor in the degradation rate of MB. Optimization studies suggest minimizing the corrugation half-angle to improve reactor performance for a given area, increasing the number of corrugations rather than the corrugation depth subject to practical limitations arising from undesirable bubble formation at small aperture widths. Given the relevance of mass transfer to this system, future work is needed to elucidate the experimental impact of reservoir volume and geometry while validating the use of flat-plate correlations for mass transfer.

No abstract

No abstract

No abstract