THE HYDROXYLATION OF ALIPHATIC SYSTEMS

The hydroxylation of an aliphatic CH₂ can also be a metabolic step catalysed by these enzyme systems. These oxidations may take place at the end of an alkyl chain (the o-position) or at the o-1 position. An example is the hydroxylation of pentobarbital 2.23–2.24.

In another example the ethyl group of the pain-killer phenacetin 2.16 is removed via the hemi-ketal, to release paracetamol 2.15, in a pro-drug:drug relationship.

These hydroxylations may be the prelude to conjugation. For example, the tranquillizer chlorpromazine 2.25 is hydroxylated 2.26 and then converted to its sulfate ester 2.27.

Other oxidations brought about by these mixed function oxidases involve the conversion of amino and amide groups to amine oxides and hydroxylamines. Thioethers are converted to sulfoxides and sulfones. Examples of the former include the conversion of nicotine 2.29 to its Noxide 2.30 while the thiazine of chlorpromazine 2.25 is converted to a sulfoxide 2.28. These oxidations can also lead to dealkylation of nitrogen, for example, in the removal of one of the methyl groups from the nitrogen of chlorpromazine 2.25.

The alcohol dehydrogenase is another important oxidative system in drug metabolism.