Cross pathway regulation: effect of histidine on the synthesis and activity of enzymes of aromatic acid biosynthesis in Bacillus subtilis.
l-Histidine and, to a lesser degree, l-phenylalanine at concentrations of 10(-4)m inhibit the growth of leaky mutants (bradytrophs) of Bacillus subtilis that are deficient in the synthesis of p-hydroxyphenylpyruvate, the first intermediate specific to tyrosine synthesis. The inhibition can be overcome by growth factor amounts of l-tyrosine and p-hydroxyphenylpyruvate. Histidine and phenylalanine are capable of inhibiting the synthesis of tyrosine in several ways, and the major physiological effect which results in growth inhibition has not been established. Both l-histidine and l-phenylalanine inhibit the activity of prephenate dehydrogenase at concentrations about 100-fold higher than the inhibitory concentration of l-tyrosine. Histidine also appears to repress the synthesis of prephenate dehydrogenase because a histidine bradytroph growing in histidine-supplemented medium has a twofold lower level of this enzyme than the same cells growing in unsupplemented medium. These same two amino acids also inhibit the growth of a bradytroph deficient in dehydroquinate synthetase, an early enzyme in the pathway of tyrosine, phenylalanine, and tryptophan synthesis. The inhibition is overcome by a combination of tyrosine and phenylalanine. Histidine-resistant derivatives of both the prephenate dehydrogenase and dehydroquinate synthetase-deficient strains, which simultaneously have gained resistance to phenylalanine, have been isolated. Most of these resistant mutants synthesize additional tyrosine compared with the parent strain. One class of resistant mutants excretes tyrosine and has a number of enzymes of aromatic acid synthesis which are no longer repressible by any combination of the aromatic amino acids. Tyrosine inhibits the growth of histidine bradytrophs. Histidine, at growth factor levels, overcomes the inhibition.
D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids; D004794:Enzyme Repression; D006539:Heptoses; D006639:Histidine / Q000494:pharmacology; D008025:Ligases; D009154:Mutation; D010088:Oxidoreductases / Q000378:metabolism; D010649:Phenylalanine / Q000494:pharmacology; D010770:Phosphotransferases; D011773:Pyruvates; D012765:Shikimic Acid; D014443:Tyrosine / Q000096:biosynthesis
D003509:Cyclohexanecarboxylic Acids; D006539:Heptoses; D011773:Pyruvates; D012765:Shikimic Acid; D014443:Tyrosine; D010649:Phenylalanine; D006639:Histidine; D010088:Oxidoreductases; D010770:Phosphotransferases; D008025:Ligases