Metabolomics of dietary fatty acid restriction in patients with phenylketonuria

PLoS One. 2012;7(8):e43021. doi: 10.1371/journal.pone.0043021. Epub 2012 Aug 13.

Abstract

Background: Patients with phenylketonuria (PKU) have to follow a lifelong phenylalanine restricted diet. This type of diet markedly reduces the intake of saturated and unsaturated fatty acids especially long chain polyunsaturated fatty acids (LC-PUFA). Long-chain saturated fatty acids are substrates of mitochondrial fatty acid oxidation for acetyl-CoA production. LC-PUFA are discussed to affect inflammatory and haemostaseological processes in health and disease. The influence of the long term PKU diet on fatty acid metabolism with a special focus on platelet eicosanoid metabolism has been investigated in the study presented here.

Methodology/principal findings: 12 children with PKU under good metabolic control and 8 healthy controls were included. Activated fatty acids (acylcarnitines C6-C18) in dried blood and the cholesterol metabolism in serum were analyzed by liquid chromatographic tandem mass spectrometry (LC-MS/MS). Fatty acid composition of plasma glycerophospholipids was determined by gas chromatography. LC-PUFA metabolites were analyzed in supernatants by LC-MS/MS before and after platelet activation and aggregation using a standardized protocol. Patients with PKU had significantly lower free carnitine and lower activated fatty acids in dried blood compared to controls. Phytosterols as marker of cholesterol (re-) absorption were not influenced by the dietary fatty acid restriction. Fatty acid composition in glycerophospholipids was comparable to that of healthy controls. However, patients with PKU showed significantly increased concentrations of y-linolenic acid (C18:3n-6) a precursor of arachidonic acid. In the PKU patients significantly higher platelet counts were observed. After activation with collagen platelet aggregation and thromboxane B(2) and thromboxane B(3) release did not differ from that of healthy controls.

Conclusion/significance: Long-term dietary fatty acid restriction influenced the intermediates of mitochondrial beta-oxidation. No functional influence on unsaturated fatty acid metabolism and platelet aggregation in patients with PKU was detected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Platelets / metabolism*
  • Carnitine / blood
  • Child
  • Chromatography, Gas
  • Chromatography, Liquid
  • Eicosanoids / metabolism*
  • Fatty Acids / blood
  • Fatty Acids / metabolism*
  • Humans
  • Metabolomics / methods*
  • Oxidation-Reduction
  • Phenylketonurias / diet therapy*
  • Phenylketonurias / metabolism*
  • Phytosterols / blood
  • Tandem Mass Spectrometry
  • gamma-Linolenic Acid / blood

Substances

  • Eicosanoids
  • Fatty Acids
  • Phytosterols
  • gamma-Linolenic Acid
  • Carnitine

Grants and funding

Junior research grant by the Medical Faculty, University of Leipzig, Germany. This publication is supported by LIFE – Leipzig Research Center for Civilization Diseases, Universität Leipzig. This project was funded by means of the European Social Fund and the Free State of Saxony. Further support was received from the Commission of the European Communities, specific RTD Programme “Quality of Life and Management of Living Resources”, within the 7th Framework Programme NUTRIMENTHE, FP7-212652. This manuscript does not necessarily reflect the views of the Commission and in no way anticipates the future policy in this area. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.