Metabolism of amphetamines by Mycobacterium smegmatis

Amphetamine and five N-alkylated homologues were readily metabolized by Mycobacterium smegmatis and the products obtained were identified by gas–liquid chromatography and mass spectrometry. The N-alkyl substituent had a considerable influence on the degree and mechanism of biotransformation. With the exception of the N-isopropyl derivative, all of the N-alkylated homologues were dealkylated to amphetamine which was then conjugated to the N-acetyl derivative. The degree of N-oxygenation of these substrates was significantly different from that observed in mammalian and fungal systems where four products are generally recovered. Mycobacterium smegmatis N-oxygenation of amphetamine did not occur, whereas all N-alkylated amphetamines were converted to the corresponding nitrones or, in the case of methamphetamine, to 1-phenyl-2-propanone oxime. No other N-oxygenated products were isolated. Mycobacterium smegmatis metabolism of 1-phenyl-2-propanone oxime, N-hydroxyamphetamine. N-hydroxy-N-(n-propyl)amphetamine, and the nitrone, α-methyl-N-(n-propylidene) benzeneethanamine N-oxide, was also studied. Some hydrolysis of the oxime to 1-phenyl-2-propanone was observed. The other three substrates were metabolized to amphetamine and N-acetylamphetamine.