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

Metabolomics of dietary fatty acid restriction in patients with phenylketonuria

Ulrike Mütze  1 , Skadi Beblo, Linda Kortz, Claudia Matthies, Berthold Koletzko, Mathias Bruegel, Carmen Rohde, Joachim Thiery, Wieland Kiess, Uta Ceglarek
Affiliations

Metabolomics of dietary fatty acid restriction in patients with phenylketonuria

Ulrike Mütze et al. PLoS One. 2012.

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Platelet count and platelet volume.
Data of patients with phenylketonuria (PKU) (n = 12) and healthy controls (n = 8). A platelet count (* p<0.05) and B platelet volume. The stripe marks the median.
Figure 2
Figure 2. Free carnitine and acylcarnitines.
Data of patients with phenylketonuria (PKU) (n = 12) and healthy controls (n = 8); measured by liquid chromatography/tandem mass spectrometry (LC-MS/MS). A Free carnitine (C0) in dried blood (**p<0.01). B Total acylcarnitines in dried blood (***p<0.001). C Octadecanoylcarnitine (C18) in dried blood (***p<0.001). D Octadecenoylcarnitine (C18:1) in dried blood (***p<0.001).
Figure 3
Figure 3. Arachidonic acid and y-linolenic acid concentrations in plasma glycerophospholipids.
Data of patients with phenylketonuria (PKU) (n = 12) and healthy controls (n = 8). A Arachidonic acid in plasma glycerophospholipids. B y-linolenic acid in plasma gylcerophospholipis (** p<0.01).
See this image and copyright information in PMC

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