Table of Contents
Journal of Amino Acids
Volume 2014, Article ID 783730, 6 pages
Research Article

Immune Activation and Inflammation in Patients with Cardiovascular Disease Are Associated with Higher Phenylalanine to Tyrosine Ratios: The Ludwigshafen Risk and Cardiovascular Health Study

1Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innrain 80, 6020 Innsbruck, Austria
2Medical Clinic V (Nephrology, Hypertensiology, Endocrinolgy, Diabetology, Rheumatology), Mannheim Medical Faculty, University of Heidelberg, 68167 Mannheim, Germany
3Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8010 Graz, Austria
4Synlab Services GmbH, Synlab Academy, 68259 Mannheim, Germany

Received 17 October 2013; Accepted 30 December 2013; Published 10 February 2014

Academic Editor: Dorothy Gietzen

Copyright © 2014 Christian Murr et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Higher serum neopterin is associated with increased mortality in patients with coronary artery disease (CAD). Preferentially Th1-type cytokine interferon-γ stimulates neopterin production by GTP cychlohydrolase 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 like phenylalanine 4-hydroxylase (PAH). Serum concentrations of phenylalanine, tyrosine, neopterin, and high sensitivity C-reactive protein (hsCRP) were measured in 1196 patients derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among patients referred for coronary angiography. The phenylalanine to tyrosine ratio (Phe/Tyr) served as an estimate of phenylalanine hydroxylase (PAH) enzyme activity. Serum concentrations of phenylalanine and tyrosine and of Phe/Tyr did not differ between individuals with or without CAD (Welch's -test: = n.s.). Higher neopterin and hsCRP concentrations were observed in CAD patients compared to controls () and they correlated with Phe/Tyr (Spearman's rank correlation for neopterin: = 0.216 and hsCRP: = 0.122; both of ) concentrations. In conclusion, immune activation is associated with higher Phe/Tyr in CAD patients. Data indicates subnormal PAH activity which might be involved in the precipitation of neuropsychiatric symptoms in patients.