Metabolic origins of the pyridones of N 1 -methylnicotinamide in man and rat

In man and rat two enzymes have been found to catalyze the formation of the pyridones of N¹-methylnicotinamide in vivo. Aldehyde oxidase, the sole apparent functionary in most mammalian species, shares its role with xanthine oxidase in these two species. Although purified xanthine oxidase had previously been shown to be capable of catalyzing the formation of N¹-methyl-2-pyridone-5-carboxamide (2-pyridone) at pH values above 8.0, this is the first documentation of such catalysis in vivo. The aldehyde oxidases of both man and the rat are like all other mammalian aldehyde oxidases in that they catalyze the formation of both 2-pyridone and N¹-methyl-4-pyridone-3-carboxamide (4-pyridone). The human and the rat liver enzymes differ from other mammalian aldehyde oxidases in that the proportions of the products vary as a function of the inactivation of these enzymes which occurs during catalysis. All of these results are compatible with the idea that, in mammals, a single enzyme, aldehyde oxidase, is capable of catalyzing the oxidation of N¹-methylnicotinamide to two alternate products and that in the rat and man xanthine oxidase can contribute to the formation of some additional 2-pyridone.