S

A second example is provided by the anticancer agent cyclophosphamide (181).208 Upon administration of 181, cytochrome P450 catalyzes hydroxylation at the 4-position, to produce 182, leading to the formation of the ring-opened aldehyde 183, or further oxidation to the cyclic amide 184 (Scheme 19). In the absence of aldehyde dehydrogenase, the aldehyde spontaneously eliminates to generate acrolein (185) and the phosphoramide mustard 186, both of which are cytotoxic species responsible for the anticancer effects. In the presence of aldehyde dehydrogenase, the ring-opened aldehyde is converted to the acid carboxyphosphamide (187), a species that no longer eliminates 185 and has no anticancer affect.

The major set of substrates for aldehyde dehydrogenase include the aldehydes generated in MAO-catalyzed deamination reactions, cytochrome P450-catalyzed N- and, O-dealkylation, oxidative dehalogenation, and oxidation of aryl and alkyl methyl groups.

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