The biochemical basis for growth inhibition by L-phenylalanine in Neisseria gonorrhoeae.
Clinical isolates of Neisseria gonorrhoeae are commonly subject to growth inhibition by phenylpyruvate or by L-phenylalanine. A blockade of tyrosine biosynthesis is indicated since inhibition is reversed by either L-tyrosine or 4-hydroxyphenylpyruvate. Phenylalanine-resistant (PheR) and phenylalanine-sensitive (PheS) isolates both have a single 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase that is partially inhibited by L-phenylalanine (80%). However, PheS and PheR isolates differ in that the ratio of phenylpyruvate aminotransferase to 4-hydroxyphenylpyruvate aminotransferase is distinctly greater in PheS isolates than in PheR isolates. A mechanism for growth inhibition is proposed in which phenylalanine exerts two interactive effects. (i) Phenylalanine decreases precursor flow to 4-hydroxyphenylpyruvate through its controlling effect upon DAHP synthase; and (ii) phenylalanine is largely transaminated to phenylpyruvate, which saturates both aminotransferases, preventing transamination of an already limited supply of 4-hydroxyphenylpyruvate to L-tyrosine.
Bhatnagar
R K
RK
Department of Microbiology and Cell Science, University of Florida, Gainesville 32611.
Berry
A
A
Hendry
A T
AT
Jensen
R A
RA
D010723:3-Deoxy-7-Phosphoheptulonate Synthase / Q000378:metabolism; D000494:Allosteric Regulation; D006131:Growth Inhibitors / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D010641:Phenotype; D010649:Phenylalanine / Q000378:metabolism / Q000494:pharmacology*; D010667:Phenylpyruvic Acids / Q000378:metabolism / Q000494:pharmacology; D000637:Transaminases / Q000378:metabolism; D014443:Tyrosine / Q000096:biosynthesis*
D006131:Growth Inhibitors; D010667:Phenylpyruvic Acids; C010590:4-hydroxyphenylpyruvic acid; D014443:Tyrosine; D010649:Phenylalanine; D010723:3-Deoxy-7-Phosphoheptulonate Synthase; D000637:Transaminases; C031606:phenylpyruvic acid