Metabolism of carnitine in phenylacetic acid-treated rats and in patients with phenylketonuria

Gabor M. Fischer, Balazs Nemeti, Viktoria Farkas, Balazs Debreceni, Aranka Laszlo, Zsuzsa Schaffer, Csilla Somogyi, Attila Sandor

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The effect of metabolites accumulating in phenylketonuria (PKU) was investigated on carnitine metabolism in rats and in patients with PKU. Of phenylacetic acid (PEAA), phenylpyruvic acid and homogentisic acid the PEAA was found to be the most effective in inhibiting carnitine biosynthesis in rats. Following 60 min, a single intraperitoneal dose of PEAA the relative conversion rate, i.e. the hydroxylation, of tracer [Me-3H]butyrobetaine to [Me-3H]carnitine decreased from 62.2±6.00% to 39.4±5.11% (means±S.E.M., P<0.01) in the liver, in the only organ doing this conversion in rats. The conversion of loading amount of unlabeled butyrobetaine to carnitine was also markedly reduced. The impaired hydroxylation of butyrobetaine was reflected by a reduced free and total carnitine levels in the liver and a reduced total carnitine concentration in the plasma. PEAA decreased the hepatic level of glutamic acid and α-ketoglutaric acid (α-KG), suggesting a mechanism for the reduced flux through the butyrobetaine hydroxylase enzyme, because α-KG is an obligatory co-enzyme. In the plasma and urine of PKU patients on unrestricted diet, markedly decreased total carnitine levels were detected. In the liver of PEAA-treated rats and urine of PKU patients, a novel carnitine derivative, phenacetyl-carnitine was verified by HPLC and gas chromatography-mass spectrometry. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)200-210
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number2-3
Publication statusPublished - Jun 15 2000



  • Benzoic acid
  • Carnitine
  • PKU
  • Phenacetylcarnitine
  • Phenylacetate
  • Phenylketonuria

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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