Metabohc polymorphisms

Genetic factors (enzyme polymorphisms, hereditary metabohc disorders)... 

Sparteine has been used as a marker of the metabohc activity of CYP2D6 (1). Pharmacokinetic studies have shown that its metabolic oxidation exhibits genetic polymorphism and that about 6-9% of the Caucasian population are poor metabohzers. Quinidine, haloperidol, and moclobemide are all potent inhibitors of the oxidative metabohsm of sparteine (2). 

Acetylation is a very common metabohc reaction, which occurs with amino, hydroxyl or sulfhydryl groups. The acetyl group is transferred from acetyl-Coenzyme A, and the reaction is catalyzed by acetyltransferases. An important aspect of this kind of substitution is the genetic polymorphism of one acetyltrans-ferase in humans, who are divided into fast and slow acetyla-tors. In a few cases, the conjugates are further metabolized to toxic compounds, as is seen with isoniazid. Some evidence exists that acetylation of the antitubercular isoniazid leads to enhanced hepatotoxicity of the drug. " Acetylation followed by hydrolysis and CYP-dependent oxidation yields free acetyl... 

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