rac-Mexiletine is an orally effective class 1b antiarrhythmic agent used to treat ventricular arrhythmias. In vivo experiments have demonstrated. It is predominantly metabolized by the liver with < 10% excreted as unchanged drug. The major mammalian metabolites have been identified as p-hydroxymexiletine (PHM) and hydroxymethylmexiletine (HMM). The purpose of our study was to determine whether ...

Previous experimental natural abundance deuterium (NAD) NMR results have shown an odd/even-related alternation in the ((2)H/(1)H) ratio of the methylene groups of fatty acids (ChemBioChem 2001, 2, 425) and, by NAD NMR in CLC, a marked difference between enantiotopic deuterons for each methylenic site (Anal. Chem. 2004, 76, 2827). However, to date, the assignment of the absolute configuration fo...

Progesterone was stereoselectively reduced to a metabolite 20alpha-hydroxy-4-pregnen-3-one in the cytosolic fraction from the liver of male mice, indicating that the reduction of progesterone is catalyzed by 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD). The cytosolic 20alpha-HSD activity was observed not only in the liver, but also in the kidney and lung. In liver cytosol, both NADPH and ...

Plant cytochrome P450s are involved in the production of over a hundred thousand metabolites such as alkaloids, terpenoids, and phenylpropanoids. Although cytochrome P450 genes constitute one of the largest superfamilies in plants, many of the catalytic functions of the enzymes they encode remain unknown. Here, we report the identification and functional characterization of a cytochrome P450 ge...

Phenylalanine ammonia-lyase (RgPAL) from Rhodotorula glutinis JN-1 stereoselectively catalyzes the conversion of the l-phenylalanine into trans-cinnamic acid and ammonia, and was used in chiral resolution of dl-phenylalanine to produce the d-phenylalanine under acidic condition. However, the optimum pH of RgPAL is 9 and the RgPAL exhibits low catalytic efficiency at acidic side. Therefore, a mu...

Background (R)-Ketamine exhibits rapid and sustained antidepressant effects in animal models of depression. It is stereoselectively metabolized to (R)-norketamine and subsequently to (2R,6R)-hydroxynorketamine in the liver. The metabolism of ketamine to hydroxynorketamine was recently demonstrated to be essential for ketamine's antidepressant actions. However, no study has compared the antidepr...

It has been found that nucleophilic reagents, i.e., NaBH4, Grignard reagents, and alkyl lithium, uniquely react with the -alkoxyor acyloxy-lactone moieties in ginkgolide and F-seco-ginkgolides to give rise to lactol derivatives. The reaction is rapid and stops at the lactol stage; the strong coordination of Na, Mg, and Li metals to the conformationally rigid cage structure is involved in both t...

The rapid firing rates and small dopamine (DA) pools that characterize mesoprefrontal DA neurons make these cells more vulnerable to release-dependent changes in intraneuronal DA levels than nigrostriatal DA neurons. In vivo studies of mesoprefrontal DA synthesis are therefore complicated by the necessity to distinguish between effects of dopaminergic drugs on synthesis-modulating autoreceptors...

Reactions of β-azolyl enamines and nitrile oxides were studied by both experimental and theoretical methods. (E)-β-(4-Nitroimidazol-5-yl), (5-nitroimidazol-4-yl) and isoxazol-5-yl enamines smoothly react regioselectively at room temperature in dioxane solution with aryl, pyridyl, and cyclohexylhydroxamoyl chlorides without a catalyst or a base to form 4-azolylisoxazoles as the only products in ...

It has been reported that breastfeeding can expose newborns to dechlorane plus (DP), but transplacental transfer of DP has not been documented. We measured DP and its dechlorinated analogs in matched maternal blood-placenta-cord blood samples from 72 residents of the e-waste recycling area of Wenling, China. DP was detected in cord sera, indicating the occurrence of prenatal DP exposure and the...