Demethylation, also

The measurement of potential Hg methylation and MeHg demethylation is significantly more complex than the measurement of HgT and MeHg concentrations in ambient samples. Methodological considerations include the maintenance of redox and temperature condition of samples during measurement, an understanding of the time course of both processes, and an understanding of the impact of spike level on the methylation and demethylation rate constants. Measurement of methylation and demethylation also requires the use of a tracer, and the abiUty to measure that trace analytically. 

In this report we will limit our discussion of chemical structure and biological activity to substituted pyridine and pyrimidine methanols which have been shown or are believed to inhibit demethylation at carbon 14, an action which leads to inhibition of demethylation, also at carbon 4. 

As already mentioned, with time the mid-molecule cleavage typical of a bifunctional catalyst decreases over the molybdenum based catalyst and the demethylation reaction becomes dominant. Demethylation also increases with increasing pressure. Amir-Ebrahimi and Rooney proposed that the metallacyclobutane isomerization mechanism should have a significant methanation and homologation contribution.34 Homologation products were not analysed in this study but have been observed in studies of the C4 and C5 reactions 35 however, methane was an important component of the cracking products over the molybdenum catalysts. 

Disposition in the Body. Readily absorbed after oral administration. It is metabolised mainly by sulphoxidation to give the side-chain sulphoxide (mesoridazine), the side-chain sulphone (sulforidazine), both of which are active, and the ring sulphoxide and sulphone A-demethylation also occurs. Other metabolites are produced by combinations of these metabolic reactions. It is metabolised in the liver, secreted in the bile, and excreted mainly in the faeces. Less than about 10% of a dose is excreted in the... 

The oxidative reactions of this sequence are catalyzed by the microsomal P-450 system [69, 70, 71]. A P-450 system from rat liver can also oxidize morphine [72]. One product of this oxidation is morphinone, a highly toxic electrophile that couples with thiol groups. The latter reaction may deplete glutathione and in other ways may account for the hepatotoxicity of morphine [73, 74]. The demethylation of codeine to morphine probably accounts for the analgesic action of codeine, and people with a defect in this demethylating system probably get no analgesia from codeine [75, 76]. Rats, too, show strain differences in the ability to demethylate codeine to morphine [77]. Quinidine, quinine, or sparteine inhibit the conversion of codeine to morphine, presumably by inhibiting the P-450 enzyme [71, 78]. While O-demethylation converts codeine to morphine, N-demethylation also occurs and produces norcodeine [79]. 

There are two pathways of degradation of DMNA by microbial enzymes and by microsomal P-450. One is denitrosation and the other demethylation. Denitrosation is a mflin microbial process for removal of DMNA from the environment, although its degradation through demethylation also takes place by a methanotroph. The reaction catalyzed by microsomal P-450 can couple with the methylation of DNA, a central paradigm for initiation of carcinogenesis. 

Solns. of anhydrous SnGl4 and benzoyl chloride in anhydrous benzene added successively to a cold (1-5°) soln. of 2,6-dimethoxyphenol in the same solvent, and kept cold for 2 days 2,6-dimethoxyphenyl benzoate. Y 92%.— This SnGl4-catalyzed 0-acylation proceeds with remarkable ease. Under more strenuous conditions, G-acylation and 0-demethylation also occur. L. H. Klemm, H. J. Wolbert, and B. T. Ho, J. Org. Ghem. 24, 952 (1959). 

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