The biochemical basis for growth inhibition by L‐phenylalanine in Neisseria gonorrhoeae

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Abstract
Summary: 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.