Effect of the α-Hydrazino Analogue of Histidine on Histidine Transport and Arginine Biosynthesis

The a-hydrazino analogue of histidine was found to be an effective inhibitor of the growth of Salmonella typhimurium wild type as well as Escherichia coli W and E. coli K-12.A mutant, hisP1650, which is resistant to the inhibitory action of the compound was isolated and found to be defective in the histidine-specific transport system.The hydrazino analogue reacts rapidly with pyridoxal phosphate in a nonenzymatic reaction to give a product which does not have the spectral properties expected of a hydrazone.The analogue inactivates several pyridoxal phosphate enzymes.Evidence is presented suggesting that the primary point of inhibition in the cell is the pyridoxal phosphate moiety of acetylornithine transaminase in the pathway of arginine biosynthesis.This communication deals with the mechanism by which the a-hydrazino analogue of histidine (Formula I) inhibits the growth of Salmonella typhimurium.A mutant resistant to the inhibitory action of this analogue was isolated and was found to be defective in the histidine-specific transport system, and therefore not able to take up 2-hydrazino-3-(4-imidazolyl)propionic acid.The data suggest that the inhibitory action of HIPA is / ?-CH 2 -CH-COOH