Dual Effects of Phenylalanine Analogs on Rabbit-Muscle Pyruvate Kinase Activity

Abstract
Rabbit muscle pyruvate kinase activity has been studied in the presence of l‐phenylalanine and its analogs: l‐phenylalanyl methyl ester (PheOMe), l‐1‐amino‐2‐phenylethyl phosphonic acid (PnPhe), l‐alanine and l‐1aminoethyl phosphonic acid (PnAla). At appropriate pH and substrate concentrations all the analogs and Phe exhibited activator and inhibitory effects at low (1–5 mM) and at high (above 5 mM) ligand concentrations respectively. Activation of pyruvate kinase by Phe and PheOMe was observed at pH above 8.2 in the presence of 2.5 mM ADP and 0.5 mM phosphoenolpyruvate (P‐pyruvate), while PnPhe activation was also observed at pH 7.5. The activatory effect followed the order: PnPhe ≫ Phe > PheOMe. All the effectors showed a mixed type of inhibition or activation with P‐pyruvate as a variable substrate and it non‐competitive inhibition or activation with ADP as a variable substrate.