Inhibition of tryptophan synthetase by indoleacrylic acid.
Indoleacrylic acid (5 x 10(-4)m in the growth medium) inhibits the growth of mycelia of Neurospora crassa and causes the cells to accumulate indoleglycerol phosphate. Measurement of kinetic parameters of partially purified tryptophan synthetase in the presence of indoleacrylic acid showed the following patterns of inhibition: in Reaction 1, the physiological reaction, indoleglycerol phosphate + serine [Formula: see text] tryptophan + glyceraldehyde-3-phosphate (unusual with respect to indoleglycerol phosphate, partially competitive with respect to serine); in Reaction 2, indole + serine [Formula: see text] tryptophan (unusual with respect to indole, partially competitive with respect to serine); in Reaction 3, indoleglycerol phosphate [Formula: see text] indole + glyceraldehyde-3-phosphate (no inhibition observed). The effects of indoleacrylic acid on whole cells were completely reversed by equimolar concentrations of tryptophan but not by indole. The addition of a 10-fold molar excess of serine to the medium completely reversed the effects. The accumulation of indoleglycerol phosphate appears to be the result of the partial blockage of tryptophan synthetase, the resulting deprivation of tryptophan, and the consequent release of its physiological feedback control on anthranilate synthetase.
D000179:Acrylates / Q000494:pharmacology; D000645:Ammonium Sulfate; D011232:Chemical Precipitation; D002850:Chromatography, Gel; D003509:Cyclohexanecarboxylic Acids; D004926:Escherichia coli / Q000201:enzymology; D005246:Feedback; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors*; D007211:Indoles / Q000494:pharmacology; D009491:Neurospora / Q000201:enzymology*; D009492:Neurospora crassa / Q000187:drug effects / Q000201:enzymology; D012694:Serine / Q000494:pharmacology; D000637:Transaminases / Q000096:biosynthesis; D014364:Tryptophan / Q000494:pharmacology; D014367:Tryptophan Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000302:isolation & purification; D062367:ortho-Aminobenzoates
D000179:Acrylates; D003509:Cyclohexanecarboxylic Acids; D007211:Indoles; D062367:ortho-Aminobenzoates; D012694:Serine; D014364:Tryptophan; D000637:Transaminases; D006836:Hydro-Lyases; D014367:Tryptophan Synthase; D000645:Ammonium Sulfate