The oxidative demethylation of monomethyl-L-amino acids.

Handler, Bernheim, and Klein (1) have shown that the oxidation of the N-methyl derivatives of nL-methionine, m-leucine, nL-alanine, and DLhistidine by rat liver and kidney preparations is due to the presence of n-amino acid oxidase, and that the N-methyl derivatives of nr,-phenylalanine, nL-tryptophan, and m,-valine are not oxidized by these preparations. Blanchard, Green, Nocito, and Ratner (2) have found that L-amino acid oxidase obtained from rat kidney and liver catalyze the oxidation of the N-methylamino acids, viz. those of L-leucine, methionine, homocysteine, and S-benzylhomocysteine, to their corresponding keto acids and methylamine. Ratner, Nocito, and Green (3) have reported that glycine oxidase, which has been found in the liver or kidney of animals, catalyzes the aerobic oxidation of sarcosine to glyoxylic acid and methylamine. Although these oxidations of N-monomethylamino acids are all oxidative demethylaminations, Handler, Bernheim, and Klein (4) have presented further evidence of the direct demethylation of sarcosine. Sarcosine oxidase which was found in rat, rabbit, and guinea pig livers oxidatively demethylates sarcosine to glycine and formaldehyde. During the course of our investigations of the metabolism of N-methyl derivatives of amino acids, it has been demonstrated that the broken cell preparations of the kidney and liver of the rabbit, guinea pig, pigeon, and hen oxidize the N-methyl-L-tryptophan, obtained from Abrus precatorius, to L-tryptophan and formaldehyde by the direct demethylation which was due to the presence of demethylase (5). Furthermore it has been shown that demethylase is a flavoprotein (6) which can be resolved into a protein and adenine-flavin-dinucleotide. Recently, in the course of our studies on the specificity of demethylase, it was evident that demethylase can also demethylate other N-monomethyl-L-amino acids, which have been tested, to their corresponding amino acids and formaldehyde and cannot oxidize N-monomethyl-n-amino acids and N-dimethylamino acids. Some of the results are given in Table I.