Zeitschrift für Naturforschung 49c: 781-790 (1994)

Phenylalanine analogues: Potent inhibitors of phenylalanine ammonia-lyase are weak inhibitors of phenylalanine-tRNA synthetases

Gerhard Leubner-Metzger and Nikolaus Amrhein

Institute of Plant Sciences, Plant Biochemistry and Physiology, Swiss Federal Institute of Technology, Sonneggstr. 5, CH-8092 Zürich, Switzerland

Received: 15 July 1994

Abstract.  (1-Amino-2-phenylethyl)phosphonic acid (APEP), (1-Amino-2-phenyl-ethyl)phosphonous acid (APEPi), alpha-aminooxy-ß-phenylpropionic acid (AOPP) and several other phenylalanine analogues are potent inhibitors of (S)-phenylalanine ammonia-lyase (PAL) in vitro and in vivo. The ability of these compounds to inhibit (S)-phenylalanine-tRNA synthetases (PRSs) from wheat germ, soybean, and baker's yeast is investigated and compared to the inhibition of PAL. We have found APEP and APEPi to inhibit the tRNAphe-aminoacylation reactions catalyzed by the three PRSs studied in vitro in a competitive manner with respect to (S)-phenylalanine. (R)-APEP inhibits the PRSs with apparent Ki values of 144 µM for wheat germ (apparent Km for (S)-phenylalanine 5.2 µM), 130 µM for soybean (apparent Km for (S)-phenylalanine 0.9 µM), and 1096 µM for baker's yeast (apparent Km for (S)-phenylalanine 5.5 µM). The apparent Ki values for (R)-APEPi are 315 µM, 160 µM, and 117 µM, respectively. APEP and APEPi inhibit the ATP-pyrophosphate exchange reactions catalyzed by the PRSs from wheat germ and baker's yeast, but they can not be activated and serve as substrates in these reactions. AOPP has no affinity to any of the three PRSs, whereas it is a potent inhibitor of PAL. In light of our in vitro results with PRSs from different sources it appears unlikely that the PAL inhibitors we have studied have any significant inhibitory effect on the initial step of protein synthesis in vivo.

Key words:
Phenylalanine Analogues, Inhibitors, Phenylalanine Ammonia-Lyase, Phenylalanine-tRNA Synthetase

Hyperlink to: Appert, Zon, Amrhein (2003) Phytochemistry 62: 415-422
Kinetic analysis of the inhibition of phenylalanine ammonia-lyase by 2-aminoindan-2-phosphonic acid and other phenylalanine analogues

Phenylalanine analogues that are inhibitors of phenylalanine ammonia-lyase

phenylalanine analogs

Article in PDF format (4.4 MB)           Abstract          Fig. 1          Fig. 2          Tab. 1          Tab. 2          Tab. 3          Tab. 4          Phe-analogues  

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