Free asymmetric dimethylarginine (ADMA) is low in children and adolescents with classical phenylketonuria (PKU)
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Free asymmetric dimethylarginine (ADMA) is a competitive inhibitor of the nitric oxide synthases (NOS). Suppression of nitric oxide (NO) synthesis increases the risk of atherosclerosis. Nevertheless, in the condition of oxidative stress, NOS blockade by ADMA may exert protective effects. Protein metabolism is altered in patients with phenylketonuria (PKU) on dietary treatment and as shown recently, oxidative stress is high in PKU. Since free ADMA concentrations are determined by both protein metabolism and oxidative stress we hypothesized, that free ADMA levels may be elevated in PKU patients.
Sixteen patients with PKU on dietary treatment (mean age 10.1 ± 5.2 yrs), and 91 healthy children (mean age 11.6 ± 3.7 yrs) participated in a cross sectional study.
ADMA, total homocysteine (tHcy) and blood glucose were lower and the L-arginine/ADMA ratio was higher in PKU patients compared to controls. No significant correlation was present between phenylalanine (Phe) concentrations, protein intake, and lipid profile, history of cardiovascular disease or ADMA.
In contrast to our hypothesis, ADMA was lower and the L-arginine/ADMA ratio was higher in PKU patients. Therefore, in PKU patients, the regulating function of ADMA on NO synthesis is altered and may thus contribute to oxidative stress.
KeywordsNitric Oxide Nitric Oxide Synthases ADMA Level Phenylalanine Hydroxylase ADMA Concentration
high density lipoprotein
nitric oxide synthase(s)
We are indebted to all study participants and their families, to the Dept. of Anesthesia and ENT at the Landeskrankenhaus Feldkirch, to the participating Pediatricians and Mrs. Helbok-Blum for their support. We gratefully acknowledge the Federal Government of Vorarlberg for financial support of our work.
Details of funding
The work has been funded by the Federal Government of Vorarlberg, Austria. The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.
- Ellger B, Richir MC, van Leeuwen PA, Debaveye Y, Langouche L, Vanhorebeek I, Teerlink T, Van den Berghe G (2008) Glycemic control modulates arginine and asymmetrical-dimethylarginine levels during critical illness by preserving dimethylarginine-dimethylaminohydrolase activity. Endocrinology 149:3148–3157PubMedCrossRefGoogle Scholar
- Engler MM, Engler MB, Malloy M, Chiu E, Besio D, Paul S, Stuehlinger M, Morrow J, Ridker P, Rifai N, Mietus-Snyder M (2004) Docosahexaenoic acid restores endothelial function in children with hyperlipidemia: results from the EARLY study. Int J Clin Pharmacol Ther 42:672–679PubMedCrossRefGoogle Scholar
- Kanzelmeyer N, Tsikas D, Chobanyan-Jürgens K, Beckmann B, Vaske B, Illsinger S, Das AM, Lücke T (2011) Asymmetric dimethylarginine in children with homocystinuria or phenylketonuria. Amino Acids doi: 10.1007/s00726-011-0892-4 [Epub ahead of print]
- Pitocco D, Zaccardi F, DI Stasio E, Romitelli F, Martini F, Scaglione GL, Speranza D, Santini S, Zuppi C, Ghirlanda G (2009) Role of asymmetric-dimethyl-L-arginine (ADMA) and nitrite/nitrate (NOx) in the pathogenesis of oxidative stress in female subjects with uncomplicated type 1 diabetes mellitus. Diab Res Clin Practice 86:173–176CrossRefGoogle Scholar
- 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. Mol Genet Metab 103:220–225PubMedCrossRefGoogle Scholar
- Schulze F, Lenzen H, Hanefeld C, Bartling A, Osterziel KJ, Goudeva L, Schmidt-Lucke C, Kusus M, Maas R, Schwedhelm E, Strödter D, Simon BC, Mügge A, Daniel WG, Tillmanns H, Maisch B, Streichert T, Böger RH (2006) Asymmetric dimethylarginine is an independent risk factor for coronary heart disease: results from the multicenter Coronary Artery Risk Determination investigating the Influence of ADMA Concentration (CARDIAC) study. Am Heart J 152(493):e1–e8PubMedGoogle Scholar