Role of tyrosine isomers in acute and chronic diseases leading to oxidative stress - A review

Gergö A. Molnar, Szilard Kun, Eszter Selley, Melinda Kertesz, Livia Szelig, Csaba Csontos, Katalin Boddi, Lajos Bogar, Attila Miseta, Istvan Wittmann

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

Oxidative stress plays a major role in the pathogenesis of a variety of acute and chronic diseases. Measurement of the oxidative stress-related end products may be performed, e.g. that of structural isomers of the physiological para-tyrosine, namely meta- and ortho-tyrosine, that are oxidized derivatives of phenylalanine. Recent data suggest that in sepsis, serum level of meta-tyrosine increases, which peaks on the 2nd and 3rd days (p<0.05 vs. controls), and the kinetics follows the intensity of the systemic inflammation correlating with serum procalcitonin levels. In a similar study subset, urinary meta-tyrosine excretion correlated with both need of daily insulin dose and the insulin-glucose product in non-diabetic septic cases (p<0.01 for both). Using linear regression model, meta-tyrosine excretion, urinary meta-tyrosine/para-tyrosine, urinary ortho-tyrosine/para-tyrosine and urinary (meta- + orthotyrosine)/ para-tyrosine proved to be markers of carbohydrate homeostasis. In a chronic rodent model, we tried to compensate the abnormal tyrosine isomers using para-tyrosine, the physiological amino acid. Rats were fed a standard high cholesterol-diet, and were given para-tyrosine or vehicle orally. High-cholesterol feeding lead to a significant increase in aortic wall meta-tyrosine content and a decreased vasorelaxation of the aorta to insulin and the glucagon-like peptide-1 analogue, liraglutide, that both could be prevented by administration of para-tyrosine. Concluding, these data suggest that meta- and ortho-tyrosine are potential markers of oxidative stress in acute diseases related to oxidative stress, and may also interfere with insulin action in septic humans. Competition of meta- and ortho-tyrosine by supplementation of para-tyrosine may exert a protective role in oxidative stress-related diseases.

Original languageEnglish
Pages (from-to)667-685
Number of pages19
JournalCurrent medicinal chemistry
Volume23
Issue number7
DOIs
Publication statusPublished - Feb 1 2016

Keywords

  • Carbohydrate metabolism
  • Hormone resistance
  • Inflammation
  • Meta-tyrosine
  • Ortho-tyrosine
  • Oxidative stress
  • Para-tyrosine
  • Sepsis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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