TY - JOUR
T1 - Experimental evidence that phenylalanine is strongly associated to oxidative stress in adolescents and adults with phenylketonuria
AU - Sanayama, Yoshitami
AU - Nagasaka, Hironori
AU - Takayanagi, Masaki
AU - Ohura, Toshihiro
AU - Sakamoto, Osamu
AU - Ito, Tetsuya
AU - Ishige-Wada, Mika
AU - Usui, Hiromi
AU - Yoshino, Makoto
AU - Ohtake, Akira
AU - Yorifuji, Tohru
AU - Tsukahara, Hirokazu
AU - Hirayama, Satoshi
AU - Miida, Takashi
AU - Fukui, Mitsuru
AU - Okano, Yoshiyuki
N1 - Funding Information:
This study was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Ministry of Health, Labor and Welfare of Japan , and by funds from Suyama Research Foundation .
PY - 2011/7
Y1 - 2011/7
N2 - 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 700-800μmol/l. Plasma anti-oxidant substances, beta-carotene, and coenzyme Q10 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 700-800μmol/l even in adult patients.
AB - 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 700-800μmol/l. Plasma anti-oxidant substances, beta-carotene, and coenzyme Q10 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 700-800μmol/l even in adult patients.
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U2 - 10.1016/j.ymgme.2011.03.019
DO - 10.1016/j.ymgme.2011.03.019
M3 - Article
C2 - 21514861
AN - SCOPUS:79958048557
SN - 1096-7192
VL - 103
SP - 220
EP - 225
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 3
ER -