Choline anitmetabolites. Studies in microorganisms.

We have described previously (1) the study in vitro of a series of analogues and homologues of choline as substrates for the enzyme choline dehydrogenase. These compounds consisted of methylated and ethylated products, both simple and mixed, of ethanolamine, 1-aminopropanol-3, 2-amino-2-methylpropanol-1, 1-aminopropanol-2, and 2-amino-2-methyl1,3-propanediol, together with the parent amines. Of these compounds, only the quaternary bases, with the exception of the triethyl derivatives of ethanolamine and 1-aminopropanol-3, were oxidized appreciably by the enzyme. However, the enzyme exhibited some affinity for all the remaining compounds in that they could depress the oxidation rate of choline. Two of the most potent of these inhibitors, 2-amino-2-methylpropanol-1 and LY ,a-dimethyltriethylcholine, were found to be powerful antagonists of choline utilization, but apparently not of choline oxidation in the young rat (2). It was of interest to extend these studies to other systems involving choline to determine (a) how specific their requirements for choline are, and (b) if a choline-like compound, active in one system, is active in certain other systems. In this paper are reported the results of studies of the above compounds in a choline-requiring mutant of NeuTospoTa cTassa (strain 34486) (3-5) and in Saccharomyces carkbergensis which exhibits a decreased growth response to inositol in the presence of choline (6, 7). Unlike the results with choline dehydrogenase, ten of the twenty-one compounds exhibited no activity in these two organisms. The compounds which possessed cholinelike activity were, with two exceptions, active in both organisms. Those compounds having anti-choline activity were different for the two organisms. 8-Methylcholine is an antagonist of choline in N. crussa but exhibits choline-like activity in S. car~sbergensis; triethylcholine has choline-like activity in N. crassa but is inactive in s. caTk3beTgensis.