Formamidase Involvement in the Metabolism of Chlorphenamidine and Formetanate Acaricides1

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Abstract
Partially purified rat liver formamidase (EC no. 3.5.1.9, arylformylamine amidohydrolase) catalyzed the deformylation of certain important metabolic intermediates of chlorphenamidine ( N′ -(4-chloro-o-tolyl)- N, N -dimethyl-formamidinec) and formetanate acaricides. 4′-Chloro-o-formotoluidide and N -formyl-5-chloroanthranilic acid from chlorphenamidine were converted to 4-chloro- o- toluidine and 5-chloroantluanilic acid, respectively, and 3′-hydroxyformanilicte from formetanate was transformed to m -aminophenol. Formamidase exhibited a much lower turnover of these substrates than for N -formylkynurenine, its natural substrate. Moreover, the deformylation re actions involving xenobiotic substrates showed product inhibition. Also, the hydrolysis of N -formylkynurenine and of the acaricide metabolic intermediates by the formamidase was inhibited by the organophosphate DFP. This formamidase could be involved in the detoxification of chlorphenamidine and formetanate acaricides in vivo.

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