The Enzymatic Deamination of Amphetamine

A previous st,udy on the metabolism of amphetamine (1-phenyl-2-aminopropane), widely used as a stimulant of the central nervous system, showed that its major route of biotransformation in the rat and dog involved hydroxylation of the aromatic ring. In the rabbit, however, the compound was not hydroxylated, but was found to be transformed in another manner (2). The present report describes an enzyme system in the rabbit which deaminates amphetamine to yield phenylacetone. It will be shown that the enzyme system is localized in the microsomal fract,ion of t,he cell and requires oxygen and reduced triphosphopyridine nucleotide. Furthermore, these studies indicate that there are inhibitory factors present in the liver of the dog, rat, and guinea pig which may explain, in part, the inability of these species to deaminate amphetamine. Materials---land d-amphetamine sulfate was obtained through t,he courtesy of the Smith, Kline and French Laboratories. l-Norephedrine hydrochloride was kindly supplied by K. H. Beyer of Sharpe and Dohme. Triphosphopyridine nucleotide (TPN) and diphosphopyridine nucleotide (DPN) 80 per cent purity, glucose-6-phosphate dehydrogenase, and glucose-6-phosphate were obtained from the Sigma Chemical Company. Reduced triphosphopyridine nucleotide (TPNH) was prepared by the procedure of Kaplan et al. (3). Methods-Amphetamine, ephedrine, norephedrine, and methylamphetamine were determined by the methyl orange react.ion of Brodie and Udenfriend (4) with benzene as the ext,ractant,, as previously described (2, 5). An essentially similar procedure was used for the estimation of l-phenyl-laminopropane, l-phenyl-3-aminobutane, phenylethylamine, isonmylamine, 2-aminoheptane, and benzylamine with chloroform as t,he extractant. Tyramine was est,imated according to Udenfriend and Cooper (6) and p-