Experimental phenylketonuria: metabolic studies in rat liver.
The "in vivo" effects of L-phenylalanine on the gluconeogenic pathway in the liver of fasted rats with experimentally induced phenylketonuria-like characteristics have been investigated. Significant increases of the fructose 6-phosphate, glucose 6-phosphate and glucose concentrations were observed. The study of the effect of L-phenylalanine on the cytoplasmic and mitochondrial redox state and energy charge showed an increase in the mitochondrial NAD+/NADH ratio while the energy charge was virtually unchanged. The effects of phenylalanine and its metabolic derivatives (phenylacetate, phenylethylamine, phenyl-lactate, o-hydroxyphenylacetate and phenylpyruvate) on the activity of lactate dehydrogenase (EC 1.1.1.27), malate dehydrogenase (EC 1.1.1.37) and 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) in rat liver have been also investigated. Phenylpyruvate inhibited the lactate dehydrogenase activity with a Ki of 5.3 mM. Phenylpyruvate also inhibited both the mitochondrial (Ki = 4 mM) and cytoplasmic (Ki = 5 mM) malate dehydrogenase activities. Phenylpyruvate, phenylacetate and o-hydroxyphenylacetate inhibited the 3-hydroxybutyrate dehydrogenase activity with Ki values of 0.7, 6.0 and 9.5 mM respectively.
D000818:Animals; D004195:Disease Models, Animal; D005215:Fasting; D005260:Female; D010134:Fenclonine / Q000009:adverse effects; D005636:Fructosephosphates / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005958:Glucosephosphates / Q000378:metabolism; D006801:Humans; D006884:Hydroxybutyrate Dehydrogenase / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D010661:Phenylketonurias / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism
D005636:Fructosephosphates; D005958:Glucosephosphates; D007657:Ketone Bodies; D009243:NAD; D010649:Phenylalanine; D007770:L-Lactate Dehydrogenase; D006884:Hydroxybutyrate Dehydrogenase; D008291:Malate Dehydrogenase; D005947:Glucose; D010134:Fenclonine