Metabolism of carnitine in phenylacetic acid-treated rats and in patients with phenylketonuria
DOI: 10.1016/S0925-4439(00)00023-5
Title: Metabolism of carnitine in phenylacetic acid-treated rats and in patients with phenylketonuria
Journal Title: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Volume: 1501
Publication Date: 15 June 2000
Start Page: 200
End Page: 210
Published online: online 31 May 2000
ISSN: 0925-4439
Affiliations:

  • a Department of Biochemistry, University Medical School, Szigeti ut 12, H-7624, Pecs, Hungary

  • b Department of Pediatrics Albert Szent-Györgyi Medical University, Koranyi fasor 14-15, P.O. Box 401, H-6720, Szeged, Hungary

  • c National Institute of Pediatrics, PKU Laboratory, Cserje utca 14, P.O. Box 14, H-1277 Budapest, 23, Hungary
  • Abstract: ct 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.
    Accepted: 30 March 2000
    Received: 14 September 1999
    Revised: 21 March 2000
    Keywords: Phenylketonuria; Phenylacetate; Phenacetylcarnitine; PKU; Carnitine; Benzoic acid
    Abbreviations: PEAA, phenylacetic acid; PEAC, phenacetyl-carnitine; α-KG, α-ketoglutarate; PKU, phenylketonuria
    Email: sandor@apacs.pote.hu

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