Metabolic pathway xenobiotic alcohols

Carbonyl reduction is a metabolic pathway widely distributed in nature. Many endogenous substances, such as prostaglandins, biogenic amines, and steroids, together with xenobiotic chemicals of several varieties, are transformed to the corresponding alcohols before further metabolism and elimination. Carbonyl reduction in several continuous cell lines was investigated using metyrapone as a substrate ketone. Quercitrin was reported to inhibit carbonyl reductase. 

Carbonyl conversions provide insight into metabolic pathways activated in the metabolism of a xenobiotic, as the involved dehydrogenases belong to different metabolic pathways each. The stereoselectivities of carbonyl and alcohol bioconversions are monitored by classic chemical analysis of stereoisomer formation. Therefore, precisely defined reaction conditions are a strict prerequisite for establishing general principles of xenobiotic metabolism which are required for the highly challenging transfer to mammalian cells. 

Acylation of Xenobiotic Alcohols A Metabolic Pathway for Drug Retention... 

Acylation of xenobiotic alcohols, metabolic pathway for drug retention, 214-219... 

Various studies regarding the biotransformation of xenobiotic ketones have established that ketone reduction is an important metabolic pathway in mammalian tissue. Because carbonyl compounds are lipophilic and may be retained in tissues, their reduction to the hydrophilic alcohols and subsequent conjugation are critical to their elimination. Although ketone reductases may be closely related to the alcohol dehydrogenases, they have distinctly different properties and use NADPH as the cofactor. The metabolism of xenobiotic ketones to free alcohols or conjugated alcohols has been demonstrated for aromatic, aliphatic, alicyclic, and unsaturated ketones (e.g., naltrexone, naloxone, hydromorphone, and daunorubicin). The carbonyl reductases are distinguished by the stereospecificity of their alcohol metabolites. 

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