The effect of phenylpyruvate on pyruvate metabolism in rat brain.
1. The effect of phenylalanine and phenylpyruvate on the metabolism of pyruvate by isolated mitochondria from rat brain was investigated. 2. Phenylpyruvate inhibited the fixation of H(14)CO(3) (-) in the presence of pyruvate by intact rat brain mitochondria, whereas phenylalanine and other metabolites of this amino acid had no inhibitory effect on this process. 3. Pyruvate carboxylase activity in freeze-dried rat brain mitochondrial preparations was also inhibited only by phenylpyruvate, and a ;mixed type' inhibition was observed. 4. The K(m) for pyruvate of rat brain pyruvate carboxylase was about 0.2mm. 5. The concentration of phenylpyruvate required for a 50% inhibition of H(14)CO(3) (-) fixation by the intact mitochondria and of pyruvate carboxylase activity was dependent on the concentration of pyruvate used in the incubation medium. 6. The possible significance of inhibition of pyruvate carboxylase activity by phenylpyruvate in the brains of phenylketonuric patients is discussed.
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002247:Carbon Isotopes; D003470:Culture Media; D005612:Freeze Drying; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008025:Ligases / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D010649:Phenylalanine / Q000494:pharmacology; D010661:Phenylketonurias / Q000201:enzymology; D010667:Phenylpyruvic Acids / Q000494:pharmacology*; D011773:Pyruvates / Q000378:metabolism*; D051381:Rats
D001639:Bicarbonates; D002247:Carbon Isotopes; D003470:Culture Media; D010667:Phenylpyruvic Acids; D011773:Pyruvates; D010649:Phenylalanine; D008025:Ligases