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

• Main Authors: Mangge Harald, Schnedl Wolfgang J., Schröcksnadel Sebastian, Geisler Simon, Murr Christian, Fuchs Dietmar
• Format: Article
• Language: English
• Published: De Gruyter 2013-06-01
• Series: Pteridines
• Subjects: coronary artery disease; neopterin; phenylalanine; phenylalanine hydroxylase; tetrahydrobiopterin
• Online Access: 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.