Choline oxidase inhibitors

A more successful strategy for developing sensitive and facile assays to monitor PLCBc activity involves converting the phosphorylated headgroup into a colorimetric agent via a series of enzyme coupled reactions. For example, phosphatidylcholine hydrolysis can be easily monitored in a rapid and sensitive manner by enzymatically converting the phosphorylcholine product into a red dye through the sequential action of alkaline phosphatase, choline oxidase, and peroxidase [33]. This assay, in which 10 nmol of phosphorylcholine can be readily detected, may be executed in a 96-well format and has been utilized in deuterium isotope and solvent viscosity studies [34] and to evaluate inhibitors of PLCBc [33] and site-directed mutants of PLCBc [35,36]. 

Acetylcholineesterase and choline oxidase Electrode was developed by co-immobilization of AChE with ChO H202. Disposable sensors constructed by co-immobilization in a gelatin membrane on Pt electrode or by immobilizing AChE in polyurethane on a thick-film metallized Pt electrode. A kinetically controlled bioenzyme sensor was also used at a low activity of ChE for determining inhibitors. [75]... 

Other non-volatile nitrogenous compounds characterized in beer include tryptophol (0 8-3-6 ppm), choline (200-250 ppm), tyramine (0 15 ppm), and hordenine (2 ppm). Patients being treated for depression with monoamine oxidase inhibitors must not take alcoholic drinks (especially chianti) and yeast products, due to the build-up of toxic levels of tyramine. 

Allen and Bevan (80) have applied the SMD technique to the study of reversible inhibitors of monoamine oxidase B, and this paper will be used as an example for discussion of the constant velocity SMD pulling method. They used the Gromacs suite of biomolecular simulation programs (18) with the united-atom Gromos 43al force field to parameterize the lipid bilayer, protein, and small-molecule inhibitors. The protein was inserted into their mixed bilayer composed of phosphatidyl choline (POPC) and phosphatidyl ethanolamine (POPE) lipids in a ratio known to be consistent for a mitochondrial membrane. Each inhibitor-bound system studied was preequilibrated in a periodic box of SPC water (20) with the simulations run using the NPT ensemble at 300 K and 1 atm pressure for 20 ns. Full atomic coordinates and velocities were saved in 200-ps increments giving five replicates for each inhibitor-bound system. A dummy atom was attached to an atom (the SMD atom shown in Fig. 7) of the inhibitor nearest to the... 

Many compounds have been studied as possible inhibitors of diamine oxidase because of the finding that the so-called antihistamine drugs inhibit diamine oxidase. Ammonia (190), aliphatic monoamines (191), ephed-rine (199), and choline (191) are weak inhibitors, whereas guanidines (193), imidazole (194), basic dyes such as pyocyanine (195), methylene blue (196), and toluylene blue (195), diamines such as thiamine (197), pyridoxamine (197), piperazine (197), and diamidines (198) (such as 4,4 -diamidinostilbene and its dimethyl derivative) are potent competitive... 

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