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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 (BH 4 ), 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  t -test:  P  = n.s.). Higher neopterin and hsCRP concentrations were observed in CAD patients compared to controls ( P  < 0.0001) and they correlated with Phe/Tyr (Spearman's rank correlation for neopterin:  r    s   = 0.216 and hsCRP:  r    s   = 0.122; both of  P  < 0.0001) 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.

journal of amino acids/journal of amino acids

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