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Official Journal of the International Society of Pteridinology

Editor-in-Chief: Fuchs, Dietmar

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Volume 24, Issue 1 (Jun 2013)


Immune activation and inflammation in patients with cardiovascular disease are associated with elevated phenylalanine-to-tyrosine ratios

Harald Mangge
  • Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Wolfgang J. Schnedl / Sebastian Schröcksnadel / Simon Geisler / Christian Murr / Dietmar Fuchs
Published Online: 2013-04-26 | DOI: https://doi.org/10.1515/pterid-2013-0002


Higher serum neopterin concentrations and kynurenine-to-tryptophan (Kyn/Trp) ratios are associated with increased mortality in patients with coronary artery disease (CAD). Preferentially, Th1-type cytokine interferon-γ stimulates tryptophan breakdown and neopterin production by GTP cyclohydrolase I (GCH-I) in parallel in monocyte-derived macrophages and dendritic cells. In other cells, activation of GCH-I leads to the formation of 5,6,7,8-tetrahydrobiopterin (BH4), the necessary cofactor of amino acid hydroxylases such as phenylalanine 4-hydroxylase (PAH) and nitric oxide synthases. In 31 CAD patients (70.3±9.9 years; 21 males, 10 females), we determined serum concentrations of phenylalanine, tyrosine, and Kyn/Trp by HPLC, neopterin by ELISA, and nitrite by the colorimetric Griess assay. The phenylalanine-to-tyrosine ratio (Phe/Tyr) served as an estimate of PAH enzyme activity. Elevated Phe/Tyr concentrations were detected in a subgroup of CAD patients and correlated with Kyn/Trp (r=0.396, p<0.05) and neopterin (r=0.354, p<0.05) and inversely with nitrite (r=–0.371, p<0.05) concentrations. Higher Phe/Tyr in patients is associated with immune activation and indicates subnormal PAH activity that might be involved in the precipitation of neuropsychiatric symptoms in CAD patients.

Keywords: coronary artery disease; neopterin; phenylalanine; phenylalanine hydroxylase; tetrahydrobiopterin


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About the article

Corresponding author: Dietmar Fuchs, Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innrain 80, 6020 Innsbruck, Austria, Fax: +43-512-9003-73330

Received: 2013-02-07

Accepted: 2013-03-22

Published Online: 2013-04-26

Published in Print: 2013-06-01

Citation Information: Pteridines, ISSN (Online) 2195-4720, ISSN (Print) 0933-4807, DOI: https://doi.org/10.1515/pterid-2013-0002.

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©2013 by Walter de Gruyter Berlin Boston. Copyright Clearance Center

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