Experimental evidence that phenylalanine is strongly associated to oxidative stress in adolescents and adults with phenylketonuria

• Published in: Molecular genetics and metabolism 2011-07, Vol.103 (3), p.220-225
• Main Authors: Sanayama, Yoshitami, Nagasaka, Hironori, Takayanagi, Masaki, Ohura, Toshihiro, Sakamoto, Osamu, Ito, Tetsuya, Ishige-Wada, Mika, Usui, Hiromi, Yoshino, Makoto, Ohtake, Akira, Yorifuji, Tohru, Tsukahara, Hirokazu, Hirayama, Satoshi, Miida, Takashi, Fukui, Mitsuru, Okano, Yoshiyuki
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biomarkers - blood; Biomarkers - urine; Diet therapy; Erythrocytes - metabolism; Female; Humans; Male; Middle Aged; Nitric Oxide - blood; Oxidative Stress; Phenylalanine; Phenylalanine - blood; Phenylalanine - metabolism; Phenylketonuria; Phenylketonurias - physiopathology; Young Adult
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2011.03.019

Few studies have looked at optimal or acceptable serum phenylalanine levels in later life in patients with phenylketonuria (PKU). This study examined the oxidative stress status of adolescents and adults with PKU. Forty PKU patients aged over fifteen years were enrolled, and were compared with thirty age-matched controls. Oxidative stress markers, anti-oxidant enzyme activities in erythrocytes, and blood anti-oxidant levels were examined. Nitric oxide (NO) production was also examined as a measure of oxidative stress. Plasma thiobarbituric acid reactive species and serum malondialdehyde-modified LDL levels were significantly higher in PKU patients than control subjects, and correlated significantly with serum phenylalanine level ( P < 0.01). Plasma total anti-oxidant reactivity levels were significantly lower in the patient group, and correlated negatively with phenylalanine level ( P < 0.001). Erythrocyte superoxide dismutase and catalase activities were higher and correlated significantly with phenylalanine level ( P < 0.01). Glutathione peroxidase activity was lower and correlated negatively with phenylalanine level ( P < 0.001). The oxidative stress score calculated from these six parameters was significantly higher in patients with serum phenylalanine of 700–800 μmol/l. Plasma anti-oxidant substances, beta-carotene, and coenzyme Q 10 were also lower (P < 0.001), although the decreases did not correlate significantly with the phenylalanine level. Serum nitrite/nitrate levels, as stable NO products, were higher together with low serum asymmetric dimethylarginine, as an endogenous NO inhibitor. Oxidative stress status is closely linked with serum phenylalanine levels. Phenylalanine level in should be maintained PKU below 700–800 μmol/l even in adult patients.