Biochemical transformations as determined by competitive analogue-metabolite growth inhibitions; prevention of pantothenic acid synthesis by cysteic acid.

The study of the metabolism of cells by a method termed inhibition analysis (l-3) led to the initial proposal that the antibacterial index (4) is a function of the inhibited enzyme system which becomes the limiting factor for growth of the organism. It was further proposed that if the product of this enzyme system is supplied to the organism the analogue either becomes ineffective as a growth inhibitor or at higher concentrations affects another enzyme system. In the latter case a higher antibacterial index, corresponding to this second enzyme system, is obtained. Precursors of the metabolite may be effective in preventing inhibition of growth by the analogue over a range of concentrations, depending upon the effectiveness with which they are transformed into the metabolite. In the present investigation paralleling recent work on the inhibition of growth of Escherichia coli with hydroxyaspartic acid (l), cysteic acid was found to inhibit growth of that organism but only in the absence of p-alanine or pantothenic acid. The inhibition was competitively prevented by aspartic acid; hence, because of the structural similarity of cysteic acid and aspartic acid, it appears that the enzyme system converting aspartic acid to fl-alanine was blocked by the inhibitor. An unusual result was obtained with glutamic acid which was found in many tests to be more effective than aspartic acid in preventing the toxicity of cysteic acid. In order to investigate further what appears to be greater activity of a precursor with respect to the metabolite, tests determining the comparative effects of aspartic acid, glutamic acid, a-ketoglutaric acid, and mixtures of cu-ketoglutaric acid and aspartic acid were carried out simultaneously. Cysteic acid also inhibits the growth of Lactobacillus casei, Lactobaeillus arabinosus 17-5, and Leuconostoc mesenteroides P-60, and in all cases the inhibition is reversed competitively by aspartic acid but not by glutamic