Recent work on the formation of catechol amines in mammals hasshown that the amino acid L-DOPA (fl-3:4-dihydroXy-L-phenylalanine) is the immediate precursor of adrenaline, noradrenaline and dopamine (fl-3:4-dihydroxyphenylethylamine). DOPA is decarboxylated by DOPA decarboxylase, an enzyme present in many tissues, including chromaffin and nervous tissue (see Blaschko, 1959).Although the molecule of DOPA is believed to be devoid of intrinsic pharmacological activity in intact animals, it has in vivo some sympathomimetic actions which are believed to be due to the catechol amines produced by the decarboxylation of L-DOPA. Also, in mice and monkeys tranquillized by reserpine, large doses of DOPA have a remarkable awakening effect (Carlsson, Lindqvist & Magnusson, 1957; Everett & Toman, 1959), caused probably by the catechol amines which are formed from it.Much infcrmation is available on the substrate specificity of DOPA decarboxylase. This enzyme acts not only on 3:4-DOPA, presumably its natural substrate, but also on a number of other amino acids, mostly hydroxylated derivatives of phenylalanine. These observations, summarized elsewhere (Blaschko, 1950;Sourkes, 1955), have shown that the 2:5-and the 2:3-isomers of DOPA are readily decarboxylated by preparations of rat and guinea-pig tissues. L-Tyrosine is not decarboxylated, but its meta-hydroxy analogue (hereafter called metatyrosine) is a substrate of the mammalian enzyme, and it has recently been shown that in normal mice, rats, rabbits and dogs metatyrosine has excitatory actions, which are also thought to be due to the amine formed by the decarboxylation of the amino acid (Mitoma, Posner, Bogdanski & Udenfriend, 1957).In the present study we have first tested the substrate specificity of the DOPA decarboxylase in the mouse and then examined a number of amino acids related to 3:4-DOPA for their awakening action in mice tranquillized * Rockefeller Fellow.

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A number of compounds have been tested as substrates of, first, the amine oxidases of rabbit and guinea-pig liver and of goat, pig, horse, and dog plasma and, second, the " diamine oxidase " of pig kidney. Of the three xylylenediamines [di(aminomethyl)benzenes] tested, m-xylylenediamine was found to be a substrate of the liver oxidase. All the plasma oxidases tested acted on both m-and o-xylylenediamine. Both 3-and 4-picolylamine (3-and 4-aminomethylpyridine) were readily oxidized by the liver enzymes; all the plasma oxidases tested oxidized 2-, 3-, and 4-picolylamine. 4-Picolylamine was more rapidly oxidized by horse and dog plasma than any other substrate hitherto examined.Recent studies on the amine oxidases of mammalian plasma (Blaschko and Hawes, 1959; Blaschko, Friedman, Hawes, and Nilsson, 199) have shown that the amine oxidases in general are a class of enzymes with a great diversity of substrate specificity. The inhibitor specificities of the plasma oxidases show that they are more closely related to the classical histaminase of pig kidney, although their substrate specificity is in many ways reminiscent of that of the intracellular amine oxidase.

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