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

Yoshitami Sanayama, Hironori Nagasaka, Masaki Takayanagi, Toshihiro Ohura, Osamu Sakamoto, Tetsuya Ito, Mika Ishige-Wada, Hiromi Usui, Makoto Yoshino, Akira Ohtake, Tohru Yorifuji, Hirokazu Tsukahara, Satoshi Hirayama, Takashi Miida, Mitsuru Fukui, Yoshiyuki Okano

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)220-225
Number of pages6
JournalMolecular Genetics and Metabolism
Volume103
Issue number3
DOIs
Publication statusPublished - 01-07-2011
Externally publishedYes

Fingerprint

Phenylketonurias
Oxidative stress
Phenylalanine
Oxidative Stress
Oxidants
Serum
Nitric Oxide
coenzyme Q10
Plasmas
Erythrocytes
beta Carotene
Enzyme activity
Glutathione Peroxidase
Nitrites
Malondialdehyde
Nitrates
Catalase
Superoxide Dismutase
Blood

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

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. / Experimental evidence that phenylalanine is strongly associated to oxidative stress in adolescents and adults with phenylketonuria. In: Molecular Genetics and Metabolism. 2011 ; Vol. 103, No. 3. pp. 220-225.
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Sanayama, Y, Nagasaka, H, Takayanagi, M, Ohura, T, Sakamoto, O, Ito, T, Ishige-Wada, M, Usui, H, Yoshino, M, Ohtake, A, Yorifuji, T, Tsukahara, H, Hirayama, S, Miida, T, Fukui, M & Okano, Y 2011, 'Experimental evidence that phenylalanine is strongly associated to oxidative stress in adolescents and adults with phenylketonuria', Molecular Genetics and Metabolism, vol. 103, no. 3, pp. 220-225. https://doi.org/10.1016/j.ymgme.2011.03.019

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

In: Molecular Genetics and Metabolism, Vol. 103, No. 3, 01.07.2011, p. 220-225.

Research output: Contribution to journalArticle

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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

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