Canavanine and Homoarginine as Antimetabolites of Arginine and Lysine in Yeast and Algae

Canavanine, which is known to occur in both the soy bean and jack bean (l), as well as in certain other higher plants (a), has been shown to inhibit the growth of Neurospora crassa (3), Escherichia coli and certain lactic acid bacteria (4), and oat coleoptile sections (5).These inhibitions were in each case reversed by arginine.With enzymes, it has been demonstrated that arginase hydrolyzes canavanine (6), and that the action of arginine desimidase on arginine is competitively inhibited by canavanine (7).More recently, it was shown in this laboratory (8) that the enzymatic formation of a new amino acid, canavaninosuccinic acid, from canavanine and fumarate, is apparently catalyzed by the same enzyme, argininosuccinase, that catalyzes the reversible reaction between arginine and fumarate to form argininosuccinate.In the presence of argininosuccinase, fumarate, arginine, and canavanine, the relative amounts of argininosuccinate and canavaninosuccinate formed depend upon t,he ratio of arginine to canavanine in the reaction mixture (8).From this evidence it would appear that inhibition of the growth of organisms by canavanine results from interference with the biosynthesis as well as the utilization of arginine.However, other evidence indicates that the mechanism of canavanine inhibition may not be this simple, at least not for all organisms inhibited by canavanine.For example, Horowitz and Srb (3) observed that lysine, as well as arginine, reverses canavanine inhibition of Neurospora, a fact not readily explainable on the above basis.The work reported here was undertaken in an attempt to throw further light on the mechanisms of canavanine inhibition and its reversal.As a result of this study, new and interesting metabolite-antimetabolite relations among certain basic amino acids were observed.Of particular interest is the behavior of homoarginine, hitherto not noted for marked biological activity (9, 10).Depending upon the microorganism employed, homoarginine acts as a potent reversing agent for canavanine inhibition, has no effect on the organism, or acts as a powerful growth inhibitor. Methods and MaterialsOrgaTzisms-The organisms employed for quantitative inhibition studies were the green alga, Chlorella vulgaris (Columbia strain), kindly supplied 207